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Sample records for therapeutic hpv dna

  1. Therapeutic HPV DNA vaccines

    Science.gov (United States)

    Lin, Ken; Roosinovich, Elena; Ma, Barbara; Hung, Chien-Fu

    2010-01-01

    It is now well established that most cervical cancers are causally associated with HPV infection. This realization has led to efforts to control HPV-associated malignancy through prevention or treatment of HPV infection. Currently, commercially available HPV vaccines are not designed to control established HPV infection and associated premalignant and malignant lesions. To treat and eradicate pre-existing HPV infections and associated lesions which remain prevalent in the U.S. and worldwide, effective therapeutic HPV vaccines are needed. DNA vaccination has emerged as a particularly promising form of therapeutic HPV vaccines due to its safety, stability and ability to induce antigen-specific immunity. This review focuses on improving the potency of therapeutic HPV vaccines through modification of dendritic cells (DCs) by [1] increasing the number of antigen-expressing/antigen-loaded DCs, [2] improving HPV antigen expression, processing and presentation in DCs, and [3] enhancing DC and T cell interaction. Continued improvement in therapeutic HPV DNA vaccines may ultimately lead to an effective DNA vaccine for the treatment of HPV-associated malignancies. PMID:20066511

  2. Fusion of CTLA-4 with HPV16 E7 and E6 enhanced the potency of therapeutic HPV DNA vaccine.

    Directory of Open Access Journals (Sweden)

    Lili Gan

    Full Text Available Preventive anti-HPV vaccines are effective against HPV infection but not against existing HPV-associated diseases, including cervical cancer and other malignant diseases. Therefore, the development of therapeutic vaccines is urgently needed. To improve anti-tumor effects of therapeutic vaccine, we fused cytotoxic T-lymphocyte antigen 4 (CTLA-4 with HPV16 E7 and E6 as a fusion therapeutic DNA vaccine (pCTLA4-E7E6. pCTLA4-E7E6 induced significantly higher anti-E7E6 specific antibodies and relatively stronger specific CTL responses than the nonfusion DNA vaccine pE7E6 in C57BL/6 mice bearing with TC-1 tumors. pCTLA4-E7E6 showed relatively stronger anti-tumor effects than pE7E6 in therapeutic immunization. These results suggest that fusing CTLA-4 with E7E6 is a useful strategy to develop therapeutic HPV DNA vaccines. In addition, fusing the C-terminal of E7 with the N-terminal of E6 impaired the functions of both E7 and E6.

  3. Fusion of CTLA-4 with HPV16 E7 and E6 enhanced the potency of therapeutic HPV DNA vaccine.

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    Gan, Lili; Jia, Rong; Zhou, Lili; Guo, Jihua; Fan, Mingwen

    2014-01-01

    Preventive anti-HPV vaccines are effective against HPV infection but not against existing HPV-associated diseases, including cervical cancer and other malignant diseases. Therefore, the development of therapeutic vaccines is urgently needed. To improve anti-tumor effects of therapeutic vaccine, we fused cytotoxic T-lymphocyte antigen 4 (CTLA-4) with HPV16 E7 and E6 as a fusion therapeutic DNA vaccine (pCTLA4-E7E6). pCTLA4-E7E6 induced significantly higher anti-E7E6 specific antibodies and relatively stronger specific CTL responses than the nonfusion DNA vaccine pE7E6 in C57BL/6 mice bearing with TC-1 tumors. pCTLA4-E7E6 showed relatively stronger anti-tumor effects than pE7E6 in therapeutic immunization. These results suggest that fusing CTLA-4 with E7E6 is a useful strategy to develop therapeutic HPV DNA vaccines. In addition, fusing the C-terminal of E7 with the N-terminal of E6 impaired the functions of both E7 and E6.

  4. Coinjection of IL2 DNA enhances E7-specific antitumor immunity elicited by intravaginal therapeutic HPV DNA vaccination with electroporation.

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    Sun, Y; Peng, S; Yang, A; Farmer, E; Wu, T-C; Hung, C-F

    2017-07-01

    The generation and use of therapeutic human papillomavirus (HPV) DNA vaccines represent an appealing treatment method against HPV-associated cervical cancer owing to their safety and durability. Previously, we created a therapeutic HPV DNA vaccine candidate by linking the HPV16-E7 DNA sequence to calreticulin (CRT/E7), which we showed could generate significant E7-specific cytotoxic T lymphocyte (CTL)-mediated antitumor immune responses against HPV16 oncogenes expressing murine tumor model TC-1. Here we assess the therapeutic efficacy of intravaginal immunization with pcDNA3-CRT/E7 followed by electroporation. In addition, we examined whether coadministration of DNA-encoding interleukin 2 (IL2) with the pcDNA3-CRT/E7 could improve the T-cell responses elicited by pcDNA3-CRT/E7. TC-1 tumor-bearing mice vaccinated intravaginally with both pcDNA3-CRT/E7 and IL2 DNA followed by electroporation induced stronger local antitumor CTL response in comparison to mice that received other treatment regimens. Additionally, we found that coadministration of IL2 DNA with pcDNA3-CRT/E7 modified the tumor microenvironment by decreasing the population of regulatory T cells and myeloid-derived suppressor cells relative to that of CTLs. Our data demonstrate the translational potential of local administration of IL2 and pcDNA3-CRT/E7 followed by electroporation in treating cervicovaginal tumors.

  5. HPV DNA test

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    ... test; Cancer of cervix - HPV DNA test References Hacker NF. Cervical dysplasia and cancer. In: Hacker NF, Gambone JC, Hobel CJ, eds. Hacker and Moore's Essentials of Obstetrics and Gynecology . 6th ...

  6. Design of a highly effective therapeutic HPV16 E6/E7-specific DNA vaccine: optimization by different ways of sequence rearrangements (shuffling.

    Directory of Open Access Journals (Sweden)

    Fahad N Almajhdi

    Full Text Available Persistent infection with the high-risk Human Papillomavirus type 16 (HPV 16 is the causative event for the development of cervical cancer and other malignant tumors of the anogenital tract and of the head and neck. Despite many attempts to develop therapeutic vaccines no candidate has entered late clinical trials. An interesting approach is a DNA based vaccine encompassing the nucleotide sequence of the E6 and E7 viral oncoproteins. Because both proteins are consistently expressed in HPV infected cells they represent excellent targets for immune therapy. Here we report the development of 8 DNA vaccine candidates consisting of differently rearranged HPV-16 E6 and E7 sequences within one molecule providing all naturally occurring epitopes but supposedly lacking transforming activity. The HPV sequences were fused to the J-domain and the SV40 enhancer in order to increase immune responses. We demonstrate that one out of the 8 vaccine candidates induces very strong cellular E6- and E7- specific cellular immune responses in mice and, as shown in regression experiments, efficiently controls growth of HPV 16 positive syngeneic tumors. This data demonstrates the potential of this vaccine candidate to control persistent HPV 16 infection that may lead to malignant disease. It also suggests that different sequence rearrangements influence the immunogenecity by an as yet unknown mechanism.

  7. Therapeutic Vaccination for HPV Induced Cervical Cancers

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    Joeli A. Brinkman

    2007-01-01

    Full Text Available Cervical Cancer is the second leading cause of cancer–related deaths in women worldwide and is associated with Human Papillomavirus (HPV infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence.

  8. Current therapeutic vaccination and immunotherapy strategies for HPV-related diseases

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    Skeate, Joseph G.; Woodham, Andrew W.; Einstein, Mark H.; Da Silva, Diane M.; Kast, W. Martin

    2016-01-01

    ABSTRACT Carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. Human papillomavirus (HPV)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. The causal relationship between HPV infection and anogenital cancer has prompted substantial interest in the development of therapeutic vaccines against high-risk HPV types targeting the viral oncoproteins E6 and E7. This review will focus on the most recent clinical trials for immunotherapies for mucosal HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced diseases. Progress in peptide- and protein-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune checkpoint inhibition, immune response modifiers, and adoptive cell therapy for HPV will be discussed. PMID:26835746

  9. Comparison of HPV detection technologies: Hybrid capture 2, PreTect HPV-Proofer and analysis of HPV DNA viral load in HPV16, HPV18 and HPV33 E6/E7 mRNA positive specimens.

    LENUS (Irish Health Repository)

    Keegan, Helen

    2012-02-01

    Human papillomavirus (HPV) testing using molecular methods in liquid based cytology (LBC) specimens may be useful as an adjunct to cervical screening by cytology. We compared the positivity rate of the commercially available HPV DNA method hybrid capture 2 (hc2) and the commercially available E6\\/E7 mRNA method PreTect HPV-Proofer in cytological specimens (n=299). LBC specimens collected (n=299) represented the following cervical cytological disease categories: Normal (n=60), borderline nuclear abnormalities (BNA) (n=34), CIN1 (n=121), CIN2 (n=60), CIN3 (n=24). Overall, 69% (205\\/299) of the cases were positive by hc2 and 38% (112\\/299) of the cases were positive by PreTect HPV-Proofer. Concordance rates between the two tests were highest in the high-grade cytology cases (CIN2: 67% and CIN3: 83%) and the normal cytology cases (88%) and lowest in the BNA and CIN1 categories (56% and 52%). HPV DNA viral load analyses were carried out on HPV16 (n=55), HPV18 (n=9) and HPV33 (n=13) samples that were positive by PreTect HPV-Proofer. The sensitivity and specificity of PreTect HPV-Proofer and the hc2 DNA test for the detection of high-grade cytology (i.e. CIN2+) were 71.4% and 75.8% vs 100% and 43.7%, respectively. The relatively low detection rate observed by PreTect HPV-Proofer in the whole range of cytological positive cases, combined with a relatively higher specificity and PPV, suggests that PreTect HPV-Proofer may be more useful than hc2 for triage and in predicting high-grade disease.

  10. Comparing triage algorithms using HPV DNA genotyping, HPV E7 mRNA detection and cytology in high-risk HPV DNA-positive women.

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    Luttmer, Roosmarijn; Berkhof, Johannes; Dijkstra, Maaike G; van Kemenade, Folkert J; Snijders, Peter J F; Heideman, Daniëlle A M; Meijer, Chris J L M

    2015-06-01

    High-risk human papillomavirus (hrHPV) DNA positive women require triage testing to identify those with high-grade cervical intraepithelial neoplasia or cancer (≥CIN2). Comparing three triage algorithms (1) E7 mRNA testing following HPV16/18/31/33/45/52/58 genotyping (E7 mRNA test), (2) HPV16/18 DNA genotyping and (3) cytology, for ≥CIN2 detection in hrHPV DNA-positive women. hrHPV DNA-positive women aged 18-63 years visiting gynecology outpatient clinics were included in a prospective observational cohort study. From these women a cervical scrape and colposcopy-directed biopsies were obtained. Cervical scrapes were evaluated by cytology, HPV DNA genotyping by bead-based multiplex genotyping of GP5+6+-PCR-products, and presence of HPV16/18/31/33/45/52/58 E7 mRNA using nucleic acid sequence-based amplification (NASBA) in DNA positive women for respective HPV types. Sensitivities and specificities for ≥CIN2 were compared between E7 mRNA test and HPV16/18 DNA genotyping in the total group (n=348), and E7 mRNA test and cytology in a subgroup of women referred for non-cervix-related gynecological complaints (n=133). Sensitivity for ≥CIN2 of the E7 mRNA test was slightly higher than that of HPV16/18 DNA genotyping (66.9% versus 60.9%; ratio 1.10, 95% CI: 1.0002-1.21), at similar specificity (54.8% versus 52.3%; ratio 1.05, 95% CI: 0.93-1.18). Neither sensitivity nor specificity of the E7 mRNA test differed significantly from that of cytology (sensitivity: 68.8% versus 75.0%; ratio 0.92, 95% CI: 0.72-1.17; specificity: 59.4% versus 65.3%; ratio 0.91, 95% CI: 0.75-1.10). For detection of ≥CIN2 in hrHPV DNA-positive women, an algorithm including E7 mRNA testing following HPV16/18/31/33/45/52/58 DNA genotyping performs similar to HPV16/18 DNA genotyping or cytology. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Polymerase chain reaction and conventional DNA tests in detection of HPV DNA in cytologically normal and abnormal cervical scrapes

    DEFF Research Database (Denmark)

    Kalia, A.; Jalava, T.; Nieminen, P.

    1992-01-01

    Med.mikrobiologi, polymerase chain reaction, DNA tests, human papillomavirus (HPV), cervical smear, hybridisation, cytologi, affiProbe HPV test, ViraType test......Med.mikrobiologi, polymerase chain reaction, DNA tests, human papillomavirus (HPV), cervical smear, hybridisation, cytologi, affiProbe HPV test, ViraType test...

  12. Prevalence of HPV-DNA and anti-HPV antibodies in women from Girardot, Colombia.

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    Leon, Sandra; Sánchez, Ricardo; Patarroyo, Manuel A; Camargo, Milena; Mejia, Adriano; Urquiza, Mauricio; Patarroyo, Manuel E

    2009-05-01

    To assess the frequency of HPV-DNA detection, human papillomavirus (HPV) seropositivity, presence of cervical lesions, and its relationship with certain socio-demographic factors in women from Girardot, Colombia from 2006 to 2007. Nine hundred fifty-three women attending their regular Pap smear control voluntarily provided cervical cells and blood samples for HPV-DNA analysis and ELISA detection of anti-L1 peptides and virus-like particles (VLPs) antibodies after answering a questionnaire regarding sexual behaviors, number of births, smoking habits, and socio-demographic background. Twenty-six of the 953 women being examined (2.73%) presented cervical cell abnormalities. A frequency of 36.62% (95% CI: 33.52%-39.7%) HPV seropositivity was detected with peptide 18301, 35.36% (95% CI: 32.3%-38.4%) with 18283, and 32.95% (95% CI: 29.9%-36%) with 18294, whereas VLPs detected a 43% seropositivity (95% CI: 39.8%-46.2%). Antibody frequency found with all peptides was significantly higher in women having cervical abnormalities (atypical squamous cells of undetermined significance and high-grade squamous intraepithelial lesions) compared with those having normal cytologies. Peptide 18283 reported a significantly higher seropositivity (35.71%) in women >44 years old, whereas peptides 18301 and 18294 evidenced a significantly lower seropositivity in those who had never given birth. HR-HPV-DNA was detected in 157 (20.50%) of 766 cervical samples amplifying positively for the beta-globin housekeeping gene. Peptides 18283, 18294, and 18301 were more specific and more sensitive than VLPs for detecting women with HR-HPV-DNA positive cervical lesions. Therefore, they could be useful in the design of a serological test for detecting HR-HPV-infected women having cervical lesions at a risk of progressing to cervical cancer.

  13. HPV as a model for the development of prophylactic and therapeutic cancer vaccines.

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    Samara, Raed N; Khleif, Samir N

    2009-08-01

    HPV has been linked to many human malignancies and, as such, represents a major public health crisis. The understanding of HPV biology, however, has helped tremendously in developing prophylactic vaccines, which should help in decreasing mortality due to HPV infections. Understanding HPV biology has allowed researchers to use the virus as a model for the development of not only prophylactic vaccines, but also therapeutic ones. The advantages of HPV as a model stem from the limited number of proteins encoded by the HPV genome that can be targeted by vaccines, and also from the restricted expression of certain viral proteins during different stages of infection. In this review, we discuss how HPV can be used as a model for the development of both prophylactic and therapeutic vaccines.

  14. HPV DNA genotyping test in low and high grade intraephitelial lesions

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    Maria Gabriella Lepore

    2009-12-01

    Full Text Available The human papillomavirus (HPV is certainly one of the few viruses associated with cancer and is present in a significant number of cancers of the anus, penis, vagina, vulva and in almost all cervical cancers.The aim of our work is to evaluate the impact of genotypes high-risk oncogenic (HR in low-grade (LSIL and high grade (HSIL intraepithelial lesions. In it are also evaluated the impact of genotypes low oncogenic risk (LR and the percentage of non-detection (NR Papillomavirus DNA Between January 2008 and June 2009 we submitted for HPV DNA genotyping test 392 patients, seronegative for HIV1/2, of which 278 with LSIL and 114 with HSIL. In 250 patients tested positive for HPV DNA HR the type 16 is present in 102 patients (41%, the 18 in 62 (25%, the 31 in 37 patients (15%, the 33 in 13 patients (5%; also was limited the simultaneous presence of 16 and 18 (13 patients 5% The search for HPV DNA is a modern method of study of cervical pathology. Optimizes the follow-up of intraepithelial lesions and the therapeutic intervention, avoiding the dangers of over/ undertreatment and allows to monitor women treated for cervical pathology.

  15. Detection of human papillomavirus (HPV) L1 gene DNA possibly bound to particulate aluminum adjuvant in the HPV vaccine Gardasil.

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    Lee, Sin Hang

    2012-12-01

    Medical practitioners in nine countries submitted samples of Gardasil (Merck & Co.) to be tested for the presence of human papillomavirus (HPV) DNA because they suspected that residual recombinant HPV DNA left in the vaccine might have been a contributing factor leading to some of the unexplained post-vaccination side effects. A total of 16 packages of Gardasil were received from Australia, Bulgaria, France, India, New Zealand, Poland, Russia, Spain and the United States. A nested polymerase chain reaction (PCR) method using the MY09/MY11 degenerate primers for initial amplification and the GP5/GP6-based nested PCR primers for the second amplification were used to prepare the template for direct automated cycle DNA sequencing of a hypervariable segment of the HPV L1 gene which is used for manufacturing of the HPV L1 capsid protein by a DNA recombinant technology in vaccine production. Detection of HPV DNA and HPV genotyping of all positive samples were finally validated by BLAST (Basic Local Alignment Search Tool) analysis of a 45-60 bases sequence of the computer-generated electropherogram. The results showed that all 16 Gardasil samples, each with a different lot number, contained fragments of HPV-11 DNA, or HPV-18 DNA, or a DNA fragment mixture from both genotypes. The detected HPV DNA was found to be firmly bound to the insoluble, proteinase-resistant fraction, presumably of amorphous aluminum hydroxyphosphate sulfate (AAHS) nanoparticles used as adjuvant. The clinical significance of these residual HPV DNA fragments bound to a particulate mineral-based adjuvant is uncertain after intramuscular injection, and requires further investigation for vaccination safety. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. HPV

    Science.gov (United States)

    Human papillomaviruses (HPV) are a group of related viruses. They can cause warts on different parts of your body. There are ... cancer. There are two categories of sexually-transmitted HPV. Low-risk HPV can cause genital warts. High- ...

  17. [Cervix uteri lesions and human papiloma virus infection (HPV): detection and characterization of DNA/HPV using PCR (polymerase chain reaction].

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    Serra, H; Pista, A; Figueiredo, P; Urbano, A; Avilez, F; De Oliveira, C F

    2000-01-01

    The prevalence of human papillomavirus (HPV) genotypes was estimated by the polymerase chain reaction (PCR), in archival paraffin was embedded tissues. The case group consisted of 84 women aged 21-67 years (mean, 40 years) who were referred to the Department of Gynaecology (Oncology Centre, Coimbra) with citopathologically abnormal smears. This group was selected from a population of women who had undergone a screening programme (1990/94) in Central Region of Portugal. All these patients (n = 84) had a colposcopic directed cervical biopsy. HPV detection and typing was performed by the PCR method in the Department of Virology (National Health Care Institute, Lisbon). The prevalence of DNA/HPV found, concerning all epithelial cervical lesions studied and classified as squamous intra-epithelial lesions (SIL) and cervical cancer was 97.8%. On the basis of the data presented in this study, it was estimated that there was a statistically significant prevalence of low risk HPV types (HPV 6/11) in low grade SIL, 83.3%, and a statistically significant prevalence of high risk HPV types (HPV 16,18,31,33,51) in high grade SIL, 58.4%, as well as cervical cancer lesions in 100%. We conclude that there was a statistically significant difference between women with low and high grade SIL for HPV infection, with low and high risk HPV types, respectively. The risk factors for cervical cancer investigated (age at first sexual intercourse, multiple sexual partners, parity, use of oral contraceptives) were not associated to statistically significant differences concerning low grade SIL and high grade SIL. The clinical and therapeutic procedures were evaluated for the same five years (1990/94). It may be concluded that there would be no significant difference in clinical procedure for high grade lesions and cervical cancer, in which the treatment had been frequently radical (cone biopsies, simple or radical hysterectomy) and in which the HPV infection persisted frequently and was

  18. Valutazione del ruolo dell’HPV-DNA test nei programmi di prevenzione del cancro cervicale

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    Agostina Ventura; Mauro Carcheri; Emanuela Caci; Patrizia Caligiuri; Roberto Capuzzo; Ilaria Chiossone; Caterina Oliveri; Paola Milano; Rossana Cirillo; Gianni Tunesi

    2006-01-01

    Human Papillomavirus (HPV) infection is the main cause of cervical cancer and cervical intraepithelial neoplasia (CIN) worldwide. Consequently, it would be useful to evaluate HPV testing to screen for cervical cancer. Recently several molecular biological tests able to detect different HPV types and to divide into high and lowrisk group have been developed. In this study we examined HPV prevalence and genotype distribution in a group of 446 women and evaluated the role of HPV-DNA testing in c...

  19. Liquid biopsy in the diagnosis of HPV DNA in breast lesions.

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    De Carolis, Sabrina; Pellegrini, Alice; Santini, Donatella; Ceccarelli, Claudio; De Leo, Antonio; Alessandrini, Federica; Arienti, Chiara; Pignatta, Sara; Tesei, Anna; Mantovani, Vilma; Zamagni, Claudio; Taffurelli, Mario; Sansone, Pasquale; Bonafé, Massimiliano; Cricca, Monica

    2017-10-04

    HPV DNA has never been investigated in nipple discharges (ND) and serum-derived extracellular vesicles, although its presence has been reported in ductal lavage fluids and blood specimens. We analyzed 50 ND, 22 serum-derived extracellular vesicles as well as 51 pathologic breast tissues for the presence of 16 HPV DNA types. We show that the presence of HPV DNA in the ND is predictive of HPV DNA-positive breast lesions and that HPV DNA is more represented in intraductal papillomas. We also show the presence of HPV DNA in the serum-derived extracellular vesicles. Our data supports the use of liquid biopsy to detect HPV DNA in breast pathology.

  20. HPV DNA Positivity Rate and Evaluation of Cytopatological Results in Patients with Chronic Vaginal Discharge

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    Güler Ateşer

    2014-06-01

    Full Text Available Aim: There are new publications stating that chronic infection may facilitate dysplastic changes and persistence of human papillomavirus (HPV-DNA positivity. Frequency of this coincidence and cervical cytological and pathological examination results were investigated in patients with chronic vaginal discharge. Methods: One hundred three patients, who were treated at least 3 times for chronic mucopurulent discharge with accessible HPV DNA results, were analyzed retrospectively. Risk factors were identified for HPV DNA positivity. HPV DNA positive-patients were divided into two groups (positive and negative according to the presence and absence of HPV DNA. The results of cytopatological and histopathological examinations and risk factors were compared between the two groups. Results: The mean age of the patients was 35±9 years. Sixty-four percent of the patients were positive for HPV DNA. Of the HPV DNA positive patients, 41% had abnormal cytological findings, 16% had cervical intraepithelial neoplasia (CIN. Of the HPV DNA-negative patients, 16% had abnormal cytological findings and, 2 patients had CIN. There was no statistically significant difference in cervical cytological abnormalities and CIN between HPV-DNA positive and negative groups. Conclusion: In our study, the rates of HPV DNA positivity and abnormal cytopathological results among patients with chronic vaginal discharge were found to be higher than that reported in the literature. (The Me­di­cal Bul­le­tin of Ha­se­ki 2014; 52: 93-7

  1. Valutazione del ruolo dell’HPV-DNA test nei programmi di prevenzione del cancro cervicale

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    Agostina Ventura

    2006-12-01

    Full Text Available Human Papillomavirus (HPV infection is the main cause of cervical cancer and cervical intraepithelial neoplasia (CIN worldwide. Consequently, it would be useful to evaluate HPV testing to screen for cervical cancer. Recently several molecular biological tests able to detect different HPV types and to divide into high and lowrisk group have been developed. In this study we examined HPV prevalence and genotype distribution in a group of 446 women and evaluated the role of HPV-DNA testing in cervical screening programs. HPV detection and genotyping were done using a polymerase chain reaction based assay (HPV Typing test. One hundred and fiftythree of those women had HPV infection (34.5% of the patients; 23 (15% had low cancerrisk HPV DNA (LR; 116 (75.8% had hight-risk HPV types (HR and 14 (9% from both groups. 130 women (85% in this HPV-infected group had at least one high risk HPV type, and were therefore considered to be at high risk for cancer. PCR results were not completely comparable with cytological diagnosis. We conclude that a combination of HPV DNA and cytologic testing has almost 100% sensitivity and negative predictive value. The specificity of the combined test is slightly lower than the specificity of the Pap-test alone but this decrease could potentially be offset by a greater protection from neoplastic progression and cost savings available by extended screening intervals.

  2. Comparison of Onclarity Human Papillomavirus (HPV) Assay with Hybrid Capture II HPV DNA Assay for Detection of Cervical Intraepithelial Neoplasia Grade 2 and 3 Lesions

    DEFF Research Database (Denmark)

    Bottari, F; Sideri, M; Gulmini, C

    2015-01-01

    that the BD Onclarity HPV assay has sensitivity comparable to that of the HC2 assay, with a trend to an increased specificity. Moreover, as Onclarity gives the chance to discriminate between the different genotypes, we calculated the genotype prevalence and the absolute risk of CIN2+: HPV 16 was the most......Analytical and clinical performance validation is essential before introduction of a new human papillomavirus (HPV) assay into clinical practice. This study compares the new BD Onclarity HPV assay, which detects E6/E7 DNA from 14 high-risk HPV types, to the Hybrid Capture II (HC2) HPV DNA test...

  3. Effect of different concentration of HPV DNA probe immobilization for cervical cancer detection based IDE biosensor

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    Roshila, M. L.; Hashim, U.; Azizah, N.; Nadzirah, Sh.; Arshad, M. K. Md; Ruslinda, A. R.; Gopinath, Subash C. B.

    2017-03-01

    This paper principally delineates to the detection process of Human Papillomavirus (HPV) DNA test. HPV is an extremely common virus infection that infected to human by the progressions cell in the cervix cell. The types of HPV that give a most exceedingly awful infected with cervical cancer is 16 and 18 other than 31 and 45. The HPV DNA probe is immobilized with a different concentration to stabilize the sensitivity. A technique of rapid and sensitive for the HPV identification was proposed by coordinating basic DNA extraction with a quality of DNA. The extraction of the quality of DNA will make a proficiency of the discovery procedure. It will rely on the sequence of the capture probes and the way to support their attached. The fabrication, surface modification, immobilization and hybridization procedures are described by current-voltage (I-V) estimation by utilizing KEITHLEY 6487. This procedure will play out a decent affectability and selectivity of HPV discovery.

  4. Human papillomavirus (HPV types 16, 18, 31, 45 DNA loads and HPV-16 integration in persistent and transient infections in young women

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    Ferenczy Alex

    2010-11-01

    Full Text Available Abstract Background HPV burden is a predictor for high-grade cervical intraepithelial neoplasia and cancer. The natural history of HPV load in young women being recently exposed to HPV is described in this paper. Methods A total of 636 female university students were followed for 2 years. Cervical specimens with HPV-16, -18, -31, or -45 DNA by consensus PCR were further evaluated with type-specific and β-globin real-time PCR assays. Proportional hazards regression was used to estimate hazard ratios (HR of infection clearance. Generalized estimating equations assessed whether HPV loads was predictive of HPV infection at the subsequent visit. Results HPV loads were consistently higher among women Conclusions The association between HPV load and persistence is not uniform across high-risk genital genotypes. HPV-16 integration was only rarely demonstrated in young women.

  5. Temperature variable and the efficiency of sperm mediated transfection of HPV16 DNA into cells.

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    Kadze, Ruslana; Chan, Philip J; Jacobson, John D; Corselli, Johannah U; King, Alan

    2002-09-01

    To pretreat sperm at various temperatures before exposure to human papillomavirus (HPV) 16 DNA fragments and to assess the efficiency of HPV carrier sperm to transfect cumulus cells. Cumulus cells from follicular aspirates were obtained, pooled and divided into culture dishes containing Sybr Gold-stained HPV DNA carrying sperm that were either pretreated at 4 degree C, 37 degree C or 40 degree C (n = 5). The cells were incubated in 5% CO(2) in air mixture at 37 degree C for 24 hours. The efficiency of sperm to take up fluorescent HPV DNA was determined at hour 0. After incubation, cumulus cell viability was assessed using the eosin method and the percentages of fluorescent cumulus cells determined. Over half of all the cumulus cells became fluorescent with the highest percentage in the 37 degree C group. Sperm pretreated at 4 degree C had the greatest amount of HPV DNA fragments. Total sperm motility was similar for the 3 pretreatment groups. There were no differences in cumulus viability among the groups. Sperm pretreated at 37 degree C transferred the greatest amount of fluorescent HPV DNA fragments to the cumulus cells. The HPV DNA was observed in the nuclear and cytoplasmic compartments. The data suggested the possibility of sperm as a vector for the transmission of HPV DNA to the cumulus cells surrounding ovulated oocytes, which might lead to early implantation failures.

  6. Study of concentration of HPV DNA probe immobilization for cervical cancer detection based IDE biosensor

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    Roshila, M. L.; Hashim, U.; Azizah, N.

    2016-07-01

    This paper mainly illustrates regarding the detection process of Human Papillomavirus (HPV) DNA probe. HPV is the most common virus that infected to human by a sexually transmitted virus. The most common high-risk HPV are 16 and 18. Interdigitated electrode (IDE) device used as based of Titanium Dioxide (TiO2) acts as inorganic surface, where by using APTES as a linker between inorganic surface and organic surface. A strategy of rapid and sensitive for the HPV detection was proposed by integrating simple DNA extraction with a gene of DNA. The extraction of the gene of DNA will make an efficiency of the detection process. It will depend on the sequence of the capture probes and the way to support their attached. The fabrication, surface modification, immobilization and hybridization processes are characterized by current voltage (I-V) measurement by using KEITHLEY 6487. This strategy will perform a good sensitivity of HPV detection.

  7. Identification of human papillomavirus (HPV) 16 DNA integration and the ensuing patterns of methylation in HPV-associated head and neck squamous cell carcinoma cell lines.

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    Hatano, Takashi; Sano, Daisuke; Takahashi, Hideaki; Hyakusoku, Hiroshi; Isono, Yasuhiro; Shimada, Shoko; Sawakuma, Kae; Takada, Kentaro; Oikawa, Ritsuko; Watanabe, Yoshiyuki; Yamamoto, Hiroyuki; Itoh, Fumio; Myers, Jeffrey N; Oridate, Nobuhiko

    2017-04-01

    Recent studies showed that human papillomavirus (HPV) integration contributes to the genomic instability seen in HPV-associated head and neck squamous cell carcinoma (HPV-HNSCC). However, the epigenetic alterations induced after HPV integration remains unclear. To identify the molecular details of HPV16 DNA integration and the ensuing patterns of methylation in HNSCC, we performed next-generation sequencing using a target-enrichment method for the effective identification of HPV16 integration breakpoints as well as the characterization of genomic sequences adjacent to HPV16 integration breakpoints with three HPV16-related HNSCC cell lines. The DNA methylation levels of the integrated HPV16 genome and that of the adjacent human genome were also analyzed by bisulfite pyrosequencing. We found various integration loci, including novel integration sites. Integration loci were located predominantly in the intergenic region, with a significant enrichment of the microhomologous sequences between the human and HPV16 genomes at the integration breakpoints. Furthermore, various levels of methylation within both the human genome and the integrated HPV genome at the integration breakpoints in each integrant were observed. Allele-specific methylation analysis suggested that the HPV16 integrants remained hypomethylated when the flanking host genome was hypomethylated. After integration into highly methylated human genome regions, however, the HPV16 DNA became methylated. In conclusion, we found novel integration sites and methylation patterns in HPV-HNSCC using our unique method. These findings may provide insights into understanding of viral integration mechanism and virus-associated carcinogenesis of HPV-HNSCC. © 2016 UICC.

  8. Detection of HPV-16 DNA by PCR in histologically cancer free lymph nodes from patients with cervical cancer

    NARCIS (Netherlands)

    M.F.D. Baay (Marc); J. Koudstaal; H. Hollema; J.M. Duk; M.P.M. Burger; W.G.V. Quint (Wim); E. Stolz (Ernst); P. Herbrink (Paul)

    1997-01-01

    textabstractThe prognostic value of detection of human papillomavirus (HPV) type 16 DNA in histologically cancer free lymph nodes was assessed in left obturator lymph nodes from cervical cancer patients with HPV-16 positive primary tumours. HPV-16 DNA was detected by

  9. HPV DNA target hybridization concentrations studies using interdigitated electrodes (IDE) for early detection of cervical cancer

    Science.gov (United States)

    Noriani, C.; Hashim, U.; Azizah, N.; Nadzirah, Sh.; Arshad, M. K. Md; Ruslinda, A. R.; Gopinath, Subash C. B.

    2017-03-01

    Human Papillomaviruses (HPV) is the major cause of cervical cancer. HPV 16 and HPV 18 are the two types of HPV are the most HPV-associated cancers and responsible as a high-risk HPV. Cervical cancer took about 70 percent of all cases due to HPV infections. Cervical cancer mostly growth on a woman's cervix and its was developed slowly as cancer. TiO2 particles give better performance and low cost of the biosensor. The used of 3-aminopropyl triethoxysilane (APTES) will be more efficient for DNA nanochip. APTES used as absorption reaction to immobilize organic biomolecules on the inorganic surface. Furthermore, APTES provide better functionalization of the adsorption mechanism on IDE. The surface functionalized for immobilizing the DNA, which is the combination of the DNA probe and the HPV target produces high sensitivity and speed detection of the IDE. The Current-Voltage (IV) characteristic proved the sensitivity of the DNA nanochip increase as the concentration varied from 0% concentration to 24% of APTES concentration.

  10. Cross-Reactivity, Epitope Spreading, and De Novo Immune Stimulation Are Possible Mechanisms of Cross-Protection of Nonvaccine Human Papillomavirus (HPV) Types in Recipients of HPV Therapeutic Vaccines

    Science.gov (United States)

    Greenfield, William; Moerman-Herzog, Andrea; Coleman, Hannah N.

    2015-01-01

    Numerous versions of human papillomavirus (HPV) therapeutic vaccines designed to treat individuals with established HPV infection, including those with cervical intraepithelial neoplasia (CIN), are in development because approved prophylactic vaccines are not effective once HPV infection is established. As human papillomavirus 16 (HPV-16) is the most commonly detected type worldwide, all versions of HPV therapeutic vaccines contain HPV-16, and some also contain HPV-18. While these two HPV types are responsible for approximately 70% of cervical cancer cases, there are other high-risk HPV types known to cause malignancy. Therefore, it would be of interest to assess whether these HPV therapeutic vaccines may confer cross-protection against other high-risk HPV types. Data available from a few clinical trials that enrolled subjects with CINs regardless of the HPV type(s) present demonstrated clinical responses, as measured by CIN regression, in subjects with both vaccine-matched and nonvaccine HPV types. The currently available evidence demonstrating cross-reactivity, epitope spreading, and de novo immune stimulation as possible mechanisms of cross-protection conferred by investigational HPV therapeutic vaccines is discussed. PMID:25947147

  11. Comparison of the Abbott RealTime High Risk HPV with Genomica HPV Clinical Array for the detection of human papillomavirus DNA.

    Science.gov (United States)

    Sias, Catia; Garbuglia, Anna Rosa; Piselli, Pierluca; Cimaglia, Claudia; Lapa, Daniele; Del Nonno, Franca; Baiocchini, Andrea; Capobianchi, Maria Rosaria

    2013-11-01

    Human papillomavirus (HPV) has been identified as the major cause of cervical cancer worldwide and HPV DNA testing is recommended in primary cervical cancer screening. Several molecular tests for detection/typing of HPV DNA with different sensitivity and specificity are commercially available. The present study compared the performance of the Abbott RealTime High Risk HPV assay and the Genomica HPV Clinical Array CLART2 in 78 specimens (63 cervical smears and 15 rectal/urethral swabs).The typing results of the Genomica assay were in absolute agreement with each of the four possible result categories of the Abbott assay (HPV16, HPV18, Other HR HPV, not detected) in 87.2% (68/78) of the samples, with a Cohen' kappa agreement coefficient for every HR type of 0.62 (95% CI: 0.39-0.85), higher in cervical swabs (k = 0.74, 95% CI: 0.50-0.99) than in rectal/urethral swabs (k = 0.36, 95% CI: 0.00-0.82). There was an excellent agreement of the Genomica results with those of Abbott in cervical samples harbored HPV single infection (100% agreement). Nonetheless, both methods may lose sensitivity for detecting HPV types in multiple infections, giving discordant results (10/78). This underlines the importance of establishing the analytical sensitivity in HPV type detection in single and multiple HPV infections. In rectal/urethral swabs, 5 of 15 (33%) discordant cases were observed, most of which became compatible when the Genomica assay was performed starting from nucleic acid extracted with the Abbott m2000sp system. These results suggest that nucleic extraction based on the magnetic beads technique is suitable for HPV DNA detection in urethral/rectal swabs. © 2013 The Authors APMIS © 2013 APMIS.

  12. Comparison of Abbott RealTime High Risk HPV and Hybrid Capture 2 for the detection of high-risk HPV DNA in a referral population setting.

    Science.gov (United States)

    Venturoli, Simona; Leo, Elisa; Nocera, Martina; Barbieri, Daniela; Cricca, Monica; Costa, Silvano; Santini, Donatella; Zerbini, Marialuisa

    2012-02-01

    The Abbott RealTime High Risk HPV assay (ART) is an automated multiplex real-time PCR test for detection of DNA from 14 high risk (HR) HPV types in cervical specimens and simultaneous distinction of HPV16 and HPV18 from other HR-HPV. To evaluate the performance of the ART assay in specimens referred for HPV testing to our laboratory (referral population) by comparison with historical data from HC2 and INNO-LiPA as well as histological status, if available. 412 cervical specimens were collected from women between 18 and 70 years of age: 301 previously tested by HC2 without clinical data and 111 previously tested by HC2 and INNO-LiPA with histological diagnosis of CIN3+. Our study demonstrated good overall agreement between ART, HC2 and INNO-LiPA. In the group of the CIN3+ specimens HR-HPV was detected by ART in 93.07% (95% CI: 88.12-98.02), while HR-HPV detection rates with HC2 and INNO-LiPA were 91.09% (95% CI: 85.53-96.65) and 95.05% (95% CI: 90.82-99.28), respectively. The typing capability of ART for HPV16, HPV18 and a pool of twelve other HR-HPV types was investigated by comparison with INNO-LiPA demonstrating high overall assay concordance (89.81%; k 0.87). The Abbott RealTime assay showed similar clinical performance for detection of CIN3+ compared with HC2. The high level of automation and ability to identify HPV16, HPV18 and other HR-HPV make this assay a very attractive option for HR-HPV testing, potentially improving patient management by risk stratification of cytological abnormal populations. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Detection of high-risk HPV DNA in semen and its association with the quality of semen.

    Science.gov (United States)

    Rintala, M A M; Grénman, S E; Pöllänen, P P; Suominen, J J O; Syrjänen, S M

    2004-11-01

    The effects of seminal high-risk human papillomavirus (HPV) DNA were assessed on the quality of semen. Semen samples of 65 men participating in the ongoing Finnish HPV Family Study were collected. Semen analyses were done by the guidelines of the Nordic Association for Andrology. HPV DNA was detected by nested polymerase chain reaction and confirmed by Southern blot hybridization for high-risk types. Altogether, 10/65 men (15.4%) had high-risk HPV DNA positive semen sample. Seminal high-risk HPV DNA did not affect semen volume, sperm concentration, motility and vitality of spermatozoa. However, semen pH was borderline lower in HPV DNA positive than negative samples (7.4 vs 7.5). Neither oligo- nor asthenozoospermia was associated with seminal HPV DNA. In conclusion, seminal high-risk HPV DNA was detected in 15% of men. It did not affect the semen analysis, except semen pH by borderline significance. Sperm donors have not been tested for HPV infections, sperm washing does not seem to eliminate the risk of HPV transmission and the consequences of HPV in the semen are at present unknown.

  14. Evolution and taxonomic classification of human papillomavirus 16 (HPV16-related variant genomes: HPV31, HPV33, HPV35, HPV52, HPV58 and HPV67.

    Directory of Open Access Journals (Sweden)

    Zigui Chen

    Full Text Available Human papillomavirus 16 (HPV16 species group (alpha-9 of the Alphapapillomavirus genus contains HPV16, HPV31, HPV33, HPV35, HPV52, HPV58 and HPV67. These HPVs account for 75% of invasive cervical cancers worldwide. Viral variants of these HPVs differ in evolutionary history and pathogenicity. Moreover, a comprehensive nomenclature system for HPV variants is lacking, limiting comparisons between studies.DNA from cervical samples previously characterized for HPV type were obtained from multiple geographic regions to screen for novel variants. The complete 8 kb genomes of 120 variants representing the major and minor lineages of the HPV16-related alpha-9 HPV types were sequenced to capture maximum viral heterogeneity. Viral evolution was characterized by constructing phylogenic trees based on complete genomes using multiple algorithms. Maximal and viral region specific divergence was calculated by global and pairwise alignments. Variant lineages were classified and named using an alphanumeric system; the prototype genome was assigned to the A lineage for all types.The range of genome-genome sequence heterogeneity varied from 0.6% for HPV35 to 2.2% for HPV52 and included 1.4% for HPV31, 1.1% for HPV33, 1.7% for HPV58 and 1.1% for HPV67. Nucleotide differences of approximately 1.0% - 10.0% and 0.5%-1.0% of the complete genomes were used to define variant lineages and sublineages, respectively. Each gene/region differs in sequence diversity, from most variable to least variable: noncoding region 1 (NCR1 /noncoding region 2 (NCR2 >upstream regulatory region (URR> E6/E7 > E2/L2 > E1/L1.These data define maximum viral genomic heterogeneity of HPV16-related alpha-9 HPV variants. The proposed nomenclature system facilitates the comparison of variants across epidemiological studies. Sequence diversity and phylogenies of this clinically important group of HPVs provides the basis for further studies of discrete viral evolution, epidemiology, pathogenesis and

  15. HPV E6/E7 mRNA versus HPV DNA biomarker in cervical cancer screening of a group of Macedonian women.

    Science.gov (United States)

    Duvlis, Sotirija; Popovska-Jankovic, Katerina; Arsova, Zorica Sarafinovska; Memeti, Shaban; Popeska, Zaneta; Plaseska-Karanfilska, Dijana

    2015-09-01

    High risk types of human papillomaviruses E6/E7 oncogenes and their association with tumor suppressor genes products are the key factors of cervical carcinogenesis. This study proposed them as specific markers for cervical dysplasia screening. The aim of the study is to compare the clinical and prognostic significance of HPV E6/E7 mRNA as an early biomarker versus HPV DNA detection and cytology in triage of woman for cervical cancer. The study group consists of 413 women: 258 NILM, 26 ASC-US, 81 LSIL, 41 HSIL, and 7 unsatisfactory cytology. HPV4AACE screening, real-time multiplex PCR and MY09/11 consensus PCR primers methods were used for the HPV DNA detection. The real-time multiplex nucleic acid sequence-based assay (NucliSENS EasyQ HPV assay) was used for HPV E6/E7 mRNA detection of the five most common high risk HPV types in cervical cancer (16, 18, 31, 33, and 45). The results show that HPV E6/E7 mRNA testing had a higher specificity 50% (95% CI 32-67) and positive predictive value (PPV) 62% (95% CI 46-76) for CIN2+ compared to HPV DNA testing that had specificity of 18% (95% CI 7-37) and PPV 52% (95% CI 39-76) respectively. The higher specificity and PPV of HPV E6/E7 mRNA testing are valuable in predicting insignificant HPV DNA infection among cases with borderline cytological finding. It can help in avoiding aggressive procedures (biopsies and over-referral of transient HPV infections) as well as lowering patient's anxiety and follow up period. © 2015 Wiley Periodicals, Inc.

  16. Penile/anal condylomas and squamous cell cancer. A HPV DNA hybridization study.

    Science.gov (United States)

    Löning, T; Riviere, A; Henke, R P; von Preyss, S; Dörner, A

    1988-01-01

    Acuminate condylomas from the penis (n = 17) and anus (six cases), three anal/penile giant condylomas, anal Bowen's disease (four cases), and intraanal squamous cell carcinomas with associated condylomatous changes (10 cases) including two verrucous carcinoma were studied for human papillomavirus (HPV) infections with nick translated, biotinylated cDNA probes for HPV 6, 11, 16 and 18. In addition, six cases of flat white penile lesions designated as lichen sclerosus et atrophicus were examined. Reannealed complementary DNA strands were detected in situ with either immunoenzyme or immunogold protocols. The in situ hybridizations resulted in 1/6 positive penile lichenoid lesions, 12/17 positive penile acuminate condylomas, 6/6 positive anal acuminate condylomas (including two condylomas with cellular atypias), 2/3 positive giant condylomas, 1/4 positive anal bowenoid lesions, and 4/10 positive keratinized squamous cell carcinomas, two of them being verrucous carcinomas. All penile/anal condylomas and two giant condylomas harboured HPV 6 and/or 11 DNA. The five positive carcinomas (carcinoma in situ/invasive cancer) contained HPV 6 and/or 11 in two cases (including the verrucous carcinomas), and HPV 16 and/or 18 in three cases (one carcinoma in situ, two invasive carcinomas). Recurrent malignancies were seen in one case to harbour the same HPV type as the primary lesions (HPV 16). In one particular patient, a double infection with HPV 16 and HPV 18 was demonstrated in distantly located malignant tumours. Our study confirms the restrictions and the value of non-isotopic hybridization methods applied to archival tissues, and extends the knowledge on the presence and distribution of HPV infections at anogenital sites.

  17. Clustering self-organizing maps (SOM) method for human papillomavirus (HPV) DNA as the main cause of cervical cancer disease

    Science.gov (United States)

    Bustamam, A.; Aldila, D.; Fatimah, Arimbi, M. D.

    2017-07-01

    One of the most widely used clustering method, since it has advantage on its robustness, is Self-Organizing Maps (SOM) method. This paper discusses the application of SOM method on Human Papillomavirus (HPV) DNA which is the main cause of cervical cancer disease, the most dangerous cancer in developing countries. We use 18 types of HPV DNA-based on the newest complete genome. By using open-source-based program R, clustering process can separate 18 types of HPV into two different clusters. There are two types of HPV in the first cluster while 16 others in the second cluster. The analyzing result of 18 types HPV based on the malignancy of the virus (the difficultness to cure). Two of HPV types the first cluster can be classified as tame HPV, while 16 others in the second cluster are classified as vicious HPV.

  18. Double demonstration of oncogenic high risk human papilloma virus DNA and HPV-E7 protein in oral cancers.

    Science.gov (United States)

    Pannone, G; Santoro, A; Carinci, F; Bufo, P; Papagerakis, S M; Rubini, C; Campisi, G; Giovannelli, L; Contaldo, M; Serpico, R; Mazzotta, M; Lo Muzio, L

    2011-01-01

    Oncogenic HPVs are necessarily involved in cervical cancer but their role in oral carcinogenesis is debated. To detect HPV in oral cancer, 38 cases of formalin fixed-paraffin embedded OSCC were studied by both DNA genotyping (MY09/11 L1 consensus primers in combination with GP5-GP6 primer pair followed by sequencing) and immunohistochemistry (monoclonal Abs against capsid protein and HPV-E7 protein, K1H8 DAKO and clone 8C9 INVITROGEN, respectively). HPV-16 tonsil cancer was used as positive control. The overall prevalence of HPV infection in OSCCs was 10.5%. Amplification of DNA samples showed single HPV DNA infection in 3 cases (HPV16; HPV53; HPV70) and double infection in one case of cheek cancer (HPV31/HPV44). The overall HR-HPV prevalence was 7.5%. E-7 antigen was immunohistochemically detected in all HPV-positive cases. HPV+ OSCC cases showed an overall better outcome than HPV negative oral cancers, as evaluated by Kaplan-Meier curves. HPVs exert their oncogenic role after DNA integration, gene expression of E5, E6 and E7 loci and p53/pRb host proteins suppression. This study showed that HPV-E7 protein inactivating pRb is expressed in oral cancer cells infected by oncogenic HPV other than classical HR-HPV-16/18. Interestingly HPV-70, considered a low risk virus with no definite collocation in oncogenic type category, gives rise to the expression of HPV-E7 protein and inactivate pRb in oral cancer. HPV-70, as proved in current literature, is able to inactivates also p53 protein, promoting cell immortalization. HPV-53, classified as a possible high risk virus, expresses E7 protein in OSCC, contributing to oral carcinogenesis. We have identified among OSCCs, a subgroup characterized by HPV infection (10.5%). Finally, we have proved the oncogenic potential of some HPV virus types, not well known in literature.

  19. Comparison of Human Papillomavirus Detection in Urine and Cervical Samples Using High-Risk HPV DNA Testing in Northern Thailand

    OpenAIRE

    Surapan Khunamornpong; Jongkolnee Settakorn; Kornkanok Sukpan; Suree Lekawanvijit; Narisara Katruang; Sumalee Siriaunkgul

    2016-01-01

    Objective. To evaluate the performance of high-risk human papillomavirus (HPV) DNA testing in urine samples compared to that of cervical sample testing in Northern Thailand. Methods. Paired urine and cervical samples were collected during the follow-up of women with a previous positive HPV test. HPV testing was performed using the Cobas 4800 HPV Test. Linear Array assay was used for genotyping in selected cases. Results. Paired urine and cervical samples were obtained from 168 women. Of 123 p...

  20. HPV DNA and Pap smear test results in cases with and without cervical pathology.

    Science.gov (United States)

    Ozalp, Sabit Sinan; Us, Tercan; Arslan, Emine; Oge, Tufan; Kaşifoğlu, Nilgün

    2012-01-01

    The aim of the study was to determine the HPV prevalance and its relation to Pap smear, colposcopy and colposcopy directed biopsy in our region of Eskisehir, Turkey. A total of 615 women who applied to the outpatient clinic between December 2009 and December 2010 constituted our study population. All patients underwent pelvic examination and Pap smear sampling. Patients who had pathological cervical appearance or Pap smear results of ASCUS, AGUS, LSIL or HSIL were referred to colposcopy. Cervical samples for HPV DNA were taken from the patients before Pap smear sampling during the routine examination or before the colposcopic evaluation. Twenty six of 615 patients (4%) were HPV positive. Of these 26 patients, 12 were positive for HPV type 16, 3 for type 18, 3 for type 51, 2 for type 6, 1 for type 52, 1 for type 33, 1 for type 16 and type 31, 1 for type 6 and 52, 1 for type 56 and 90, 1 for type 39 and 66. In 4 patients with cervical cancer, and in 3 of 4 CIN III cases both HPV DNA and Pap smear were positive. In the Pap smear examination of 615 patients, cytology revealed 35 ASCUS (5.6%) 4 AGUS (0.6%), 2 CIN I (0.3%) results who were negative for HPV DNA. These patients with abnormal cytology (n=41) underwent colposcopy directed biopsy, there were 3 CIN I and 1 CIN III and all the other cervical biopsy results of these patients were benign (inflammation, chronic cervicitis). HPV positivity in our hospital setting is low which is compatible with other studies in Turkey. In positive HPV cases there is a good correlation between HPV type and positive cervical biopsy results.

  1. Validation study of HPV DNA detection from stained FNA smears by polymerase chain reaction

    DEFF Research Database (Denmark)

    Channir, Hani Ibrahim; Larsen, Christian Grønhøj; Ahlborn, Lise Barlebo

    2016-01-01

    BACKGROUND: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) often presents with cystic cervical metastasis and a small primary tumor localized in the palatine tonsils or base of the tongue, which is diagnostically challenging. Testing for HPV DNA in fine......-needle aspiration (FNA) smears from metastases may facilitate a targeted diagnostic workup for identifying the primary tumor. This study was designed to assess the ability to detect HPV DNA in FNA smears with polymerase chain reaction (PCR). METHODS: May-Grünvald-Giemsa (MGG)-stained FNA smears from metastases...... and corresponding surgical specimens were collected from 71 patients with known HPV-positive OPSCC, 12 patients with oral squamous cell carcinoma (OSCC), 20 patients with branchial cleft cysts, and 20 patients with Warthin tumors. Thirty-eight patients with OPSCC and 7 patients with OSCC had FNA smears available...

  2. Immunization with an HPV-16 L1-based chimeric virus-like particle containing HPV-16 E6 and E7 epitopes elicits long-lasting prophylactic and therapeutic efficacy in an HPV-16 tumor mice model.

    Science.gov (United States)

    Monroy-García, Alberto; Gómez-Lim, Miguel Angel; Weiss-Steider, Benny; Hernández-Montes, Jorge; Huerta-Yepez, Sara; Rangel-Santiago, Jesús F; Santiago-Osorio, Edelmiro; Mora García, María de Lourdes

    2014-02-01

    HPV L1-based virus-like particles vaccines (VLPs) efficiently induce temporary prophylactic activity through the induction of neutralizing antibodies; however, VLPs that can provide prophylactic as well as therapeutic properties for longer periods of time are needed. For this purpose, we generated a novel HPV 16 L1-based chimeric virus-like particle (cVLP) produced in plants that contains a string of T-cell epitopes from HPV 16 E6 and E7 fused to its C-terminus. In the present study, we analyzed the persistence of specific IgG antibodies with neutralizing activity induced by immunization with these cVLPs, as well as their therapeutic potential in a tumor model of C57BL/6 mice. We observed that these cVLPs induced persistent IgG antibodies for over 12 months, with reactivity and neutralizing activity for VLPs composed of only the HPV-16 L1 protein. Efficient protection for long periods of time and inhibition of tumor growth induced by TC-1 tumor cells expressing HPV-16 E6/E7 oncoproteins, as well as significant tumor reduction (57 %), were observed in mice immunized with these cVLPs. Finally, we discuss the possibility that chimeric particles of the type described in this work may be the basis for developing HPV prophylactic and therapeutic vaccines with high efficacy.

  3. HPV16 E7 DNA tattooing: safety, immunogenicity, and clinical response in patients with HPV-positive vulvar intraepithelial neoplasia.

    Science.gov (United States)

    Samuels, Sanne; Marijne Heeren, A; Zijlmans, Henry J M A A; Welters, Marij J P; van den Berg, Joost H; Philips, Daisy; Kvistborg, Pia; Ehsan, Ilina; Scholl, Suzy M E; Nuijen, Bastiaan; Schumacher, Ton N M; van Beurden, Marc; Jordanova, Ekaterina S; Haanen, John B A G; van der Burg, Sjoerd H; Kenter, Gemma G

    2017-09-01

    Usual type vulvar intraepithelial neoplasia (uVIN) is caused by HPV, predominantly type 16. Several forms of HPV immunotherapy have been studied, however, clinical results could be improved. A novel intradermal administration route, termed DNA tattooing, is superior in animal models, and was tested for the first time in humans with a HPV16 E7 DNA vaccine (TTFC-E7SH). The trial was designed to test safety, immunogenicity, and clinical response of TTFC-E7SH in twelve HPV16 + uVIN patients. Patients received six vaccinations via DNA tattooing. The first six patients received 0.2 mg TTFC-E7SH and the next six 2 mg TTFC-E7SH. Vaccine-specific T-cell immunity was evaluated by IFNγ-ELISPOT and multiparametric flow cytometry. Only grade I-II adverse events were observed upon TTFC-E7SH vaccination. The ELISPOT analysis showed in 4/12 patients a response to the peptide pool containing shuffled E7 peptides. Multiparametric flow cytometry showed low CD4 + and/or CD8 + T-cell responses as measured by increased expression of PD-1 (4/12 in both), CTLA-4 (2/12 and 3/12), CD107a (5/12 and 4/12), or the production of IFNγ (2/12 and 1/12), IL-2 (3/12 and 4/12), TNFα (2/12 and 1/12), and MIP1β (3/12 and 6/12). At 3 months follow-up, no clinical response was observed in any of the twelve vaccinated patients. DNA tattoo vaccination was shown to be safe. A low vaccine-induced immune response and no clinical response were observed in uVIN patients after TTFC-E7SH DNA tattoo vaccination. Therefore, a new phase I/II trial with an improved DNA vaccine format is currently in development for patients with uVIN.

  4. Clinical validation of high risk HPV DNA testing versus ThinPrep cytology for primary cervical cancer screening

    Directory of Open Access Journals (Sweden)

    Mahmoud El-Morsi Aboul-Fotouh

    2013-06-01

    Conclusions: ThinPrep smears and hr-HPV DNA detection by HC-II performed very well with regard to identifying high grade lesions. HPV DNA testing is a promising new technology for cervical cancer prevention and can be used for primary screening in conjunction with cervical cytology for women aged 30 years and older.

  5. DNA methylation profiling across the spectrum of HPV-associated anal squamous neoplasia.

    Science.gov (United States)

    Hernandez, Jonathan M; Siegel, Erin M; Riggs, Bridget; Eschrich, Steven; Elahi, Abul; Qu, Xiaotao; Ajidahun, Abidemi; Berglund, Anders; Coppola, Domenico; Grady, William M; Giuliano, Anna R; Shibata, David

    2012-01-01

    Changes in host tumor genome DNA methylation patterns are among the molecular alterations associated with HPV-related carcinogenesis. However, there is little known about the epigenetic changes associated specifically with the development of anal squamous cell cancer (SCC). We sought to characterize broad methylation profiles across the spectrum of anal squamous neoplasia. Twenty-nine formalin-fixed paraffin embedded samples from 24 patients were evaluated and included adjacent histologically normal anal mucosa (NM; n = 3), SCC-in situ (SCC-IS; n = 11) and invasive SCC (n = 15). Thirteen women and 11 men with a median age of 44 years (range 26-81) were included in the study. Using the SFP(10) LiPA HPV-typing system, HPV was detected in at least one tissue from all patients with 93% (27/29) being positive for high-risk HPV types and 14 (93%) of 15 invasive SCC tissues testing positive for HPV 16. Bisulfite-modified DNA was interrogated for methylation at 1,505 CpG loci representing 807 genes using the Illumina GoldenGate Methylation Array. When comparing the progression from normal anal mucosa and SCC-IS to invasive SCC, 22 CpG loci representing 20 genes demonstrated significant differential methylation (p<0.01). The majority of differentially methylated gene targets occurred at or close to specific chromosomal locations such as previously described HPV methylation "hotspots" and viral integration sites. We have identified a panel of differentially methlylated CpG loci across the spectrum of HPV-associated squamous neoplasia of the anus. To our knowledge, this is the first reported application of large-scale high throughput methylation analysis for the study of anal neoplasia. Our findings support further investigations into the role of host-genome methylation in HPV-associated anal carcinogenesis with implications towards enhanced diagnosis and screening strategies.

  6. DNA methylation profiling across the spectrum of HPV-associated anal squamous neoplasia.

    Directory of Open Access Journals (Sweden)

    Jonathan M Hernandez

    Full Text Available Changes in host tumor genome DNA methylation patterns are among the molecular alterations associated with HPV-related carcinogenesis. However, there is little known about the epigenetic changes associated specifically with the development of anal squamous cell cancer (SCC. We sought to characterize broad methylation profiles across the spectrum of anal squamous neoplasia.Twenty-nine formalin-fixed paraffin embedded samples from 24 patients were evaluated and included adjacent histologically normal anal mucosa (NM; n = 3, SCC-in situ (SCC-IS; n = 11 and invasive SCC (n = 15. Thirteen women and 11 men with a median age of 44 years (range 26-81 were included in the study. Using the SFP(10 LiPA HPV-typing system, HPV was detected in at least one tissue from all patients with 93% (27/29 being positive for high-risk HPV types and 14 (93% of 15 invasive SCC tissues testing positive for HPV 16. Bisulfite-modified DNA was interrogated for methylation at 1,505 CpG loci representing 807 genes using the Illumina GoldenGate Methylation Array. When comparing the progression from normal anal mucosa and SCC-IS to invasive SCC, 22 CpG loci representing 20 genes demonstrated significant differential methylation (p<0.01. The majority of differentially methylated gene targets occurred at or close to specific chromosomal locations such as previously described HPV methylation "hotspots" and viral integration sites.We have identified a panel of differentially methlylated CpG loci across the spectrum of HPV-associated squamous neoplasia of the anus. To our knowledge, this is the first reported application of large-scale high throughput methylation analysis for the study of anal neoplasia. Our findings support further investigations into the role of host-genome methylation in HPV-associated anal carcinogenesis with implications towards enhanced diagnosis and screening strategies.

  7. Down-regulation of Toll-like Receptor TLR4 Is Associated with HPV DNA Integration in Penile Carcinoma.

    Science.gov (United States)

    Damasdi, Miklos; Kovacs, Krisztina; Farkas, Nelli; Jakab, Ferenc; Kovacs, Gyula

    2017-10-01

    Development of penile cancers is attributed to HPV-related carcinogenesis. Our aim was to analyze HPV positivity and TLR4, p16(ink4a) and p53 expression. HPV presence was assessed with virus-specific TaqMan PCR and HPV Genotyping Test in 31 penile cancers. Immunohistochemistry was carried out on tissue microarray. TLR4 expression was detected in 4 of the 16 HPV positive and 13 of the 15 HPV negative tumors. We found a significant inverse correlation between HPV positivity and TLR4 expression (p=0.0006). Ten of the 16 HPV-positive but none of the 15 HPV-negative tumors expressed p16INK4a. A significant correlation was seen between p53 expression and lack of HPV DNA (p=0.0191) as well as between TLR4 and p53 expression (p=0.0198) in penile cancers. Our findings suggest a protective role of TLR4 expression against HPV DNA integration and the viral and non-viral carcinogenesis of penile cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  8. TriVax-HPV: an improved peptide-based therapeutic vaccination strategy against human papillomavirus-induced cancers.

    Science.gov (United States)

    Barrios, Kelly; Celis, Esteban

    2012-08-01

    Therapeutic vaccines for cancer are an attractive alternative to conventional therapies, since the later result in serious adverse effects and in most cases are not effective against advanced disease. Human papillomavirus (HPV) is responsible for several malignancies such as cervical carcinoma. Vaccines targeting oncogenic viral proteins like HPV16-E6 and HPV16-E7 are ideal candidates to elicit strong immune responses without generating autoimmunity because: (1) these products are not expressed in normal cells and (2) their expression is required to maintain the malignant phenotype. Our group has developed peptide vaccination strategy called TriVax, which is effective in generating vast numbers of antigen-specific T cells in mice capable of persisting for long time periods. We have used two HPV-induced mouse cancer models (TC-1 and C3.43) to evaluate the immunogenicity and therapeutic efficacy of TriVax prepared with the immunodominant CD8 T-cell epitope HPV16-E7(49-57), mixed with poly-IC adjuvant and costimulatory anti-CD40 antibodies. TriVax using HPV16-E7(49-57) induced large and persistent T-cell responses that were therapeutically effective against established HPV16-E7 expressing tumors. In most cases, TriVax was successful in attaining complete rejections of 6-11-day established tumors. In addition, TriVax induced long-term immunological memory, which prevented tumor recurrences. The anti-tumor effects of TriVax were independent of NK and CD4 T cells and, surprisingly, did not rely to a great extent on type-I or type-II interferon. These findings indicate that the TriVax strategy is an appealing immunotherapeutic approach for the treatment of established viral-induced tumors. We believe that these studies may help to launch more effective and less invasive therapeutic vaccines for HPV-mediated malignancies.

  9. Higher levels of oxidative DNA damage in cervical cells are correlated with the grade of dysplasia and HPV infection.

    Science.gov (United States)

    Visalli, Giuseppa; Riso, Romana; Facciolà, Alessio; Mondello, Placido; Caruso, Carmela; Picerno, Isa; Di Pietro, Angela; Spataro, Pasquale; Bertuccio, Maria Paola

    2016-02-01

    The Human papillomavirus is responsible for the most common sexually transmitted infection and is also known to be an oncogenic virus that is associated with cervical, anogenital, and head-neck cancers. The present study aims to assess whether oxidative DNA damage is correlated with the grade of HPV-related lesions. Moreover, we evaluated clinical data and unhealthy lifestyles to verify their possible influence on the genesis of oxidative DNA damage in cervical cells. We quantified the amount of 8-Oxo-2'-deoxyguanosine in DNA as a biomarker of oxidative damage in women with and without HPV infection. We also correlated oxidative damage with different stages of cervical lesions and available clinical data (e.g., HPV genotypes). To identify HPV infections, in which proteins with a transforming potential are produced, we performed a qualitative detection of HPV E6/E7 mRNA. Our results showed greater oxidative damage in HPV-related dysplastic cervical lesions compared to samples with normal cytology, especially in women with high-grade squamous intraepithelial lesions. The latter showed a closed link with high-risk HPV genotypes. Reactive oxygen species can induce DNA double-strand breaks in both the host DNA and in the circular viral episome; this could facilitate the integration of the virus, promoting HPV carcinogenesis. Therefore, in HPV-infected women, it could be useful to reduce additional resources of reactive oxygen/nitrogen species (RONS) with a healthy lifestyle. © 2015 Wiley Periodicals, Inc.

  10. Diagnostic Performance of HPV E6/E7 mRNA and HPV DNA Assays for the Detection and Screening of Oncogenic Human Papillomavirus Infection among Woman with Cervical Lesions in China.

    Science.gov (United States)

    Wang, Hye-young; Lee, Dongsup; Park, Sunyoung; Kim, Geehyuk; Kim, Sunghyun; Han, Lin; Yubo, Ren; Li, Yingxue; Park, Kwang Hwa; Lee, Hyeyoung

    2015-01-01

    Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and it is responsible for most cases of cervical uterine cancer. Although HPV infections of the cervix do not always progress to cancer, 90% of cervical cancer cases have been found to be associated with high risk HPV (HR- HPV) infection. HPV DNA testing is widely used, along with Papanicolaou (Pap) testing, to screen for cervical abnormalities. However, there are no data on the prevalence of genotype-specific HPV infections assessed by measuring HPV E6/E7 mRNA in women representative of the Chinese population across a broad age range. In the present study, we compared the results with the CervicGen HPV RT-qDx assay, which detects 16 HR-HPV genotypes (Alpha-9: HPV 16, 31, 33, 35, 52, and 58; Alpha-7: HPV 18, 39, 45, 51, 59, and 68; and Alpha-5, 6: HPV 53, 56, 66, and 69), and the REBA HPV-ID assay, which detects 32 HPV genotypes based on the reverse blot hybridization assay (REBA) for the detection of oncogenic HPV infection according to cytological diagnosis. We also investigated the prevalence and genotype distribution of HPV infection with a total of 324 liquid-based cytology samples collected in western Shandong province, East China. The overall HPV prevalences determined by HPV DNA and HPV E6/E7 mRNA assays in this study were 79.9% (259/324) and 55.6% (180/324), respectively. Although the positivity of HPV E6/E7 mRNA expression was significantly lower than HPV DNA positivity, the HPV E6/E7 mRNA assay showed greater specificity than the HPV DNA assay (88.6% vs. 48.1%) in normal cytology samples. The prevalence of Alpha-9 (HPV 16, 31, 33, 35, 52, and 58) HPV infection among these women accounted for up to 80.3% and 76.1% of the high-grade lesions detected in the HPV mRNA and DNA tests, respectively. The HR-HPV genotype distribution, based on HPV DNA and E6/E7 mRNA expression by age group in patients with cytologically confirmed lesions, was highest in women aged 40 to 49 years

  11. Comparison of HPV DNA testing in cervical exfoliated cells and tissue biopsies among HIV-positive women in Kenya

    OpenAIRE

    De Vuyst, Hugo; Chung, Michael H.; Baussano, Iacopo; Mugo, Nelly R.; Tenet, Vanessa; van Kemenade, Folkert J; Rana, Farzana S.; Sakr, Samah R.; Meijer, Chris J.L.M.; Snijders, Peter J.F.; Franceschi, Silvia

    2013-01-01

    HIV-positive women are infected with human papillomavirus (HPV) (especially with multiple types), and develop cervical intraepithelial neoplasia (CIN) and cervical cancer more frequently than HIV-negative women. We compared HPV DNA prevalence obtained using a GP5+/6+ PCR assay in cervical exfoliated cells to that in biopsies of 468 HIV-positive women from Nairobi, Kenya. HPV prevalence was higher in cells than biopsies and the difference was greatest in 94 women with a combination normal cyto...

  12. Liquid-based cytology and HPV DNA testing using intra-anal specimens from HIV-negative women with and without genital HPV-induced lesions.

    Science.gov (United States)

    Eleutério, José; Benício, Givanildo Carneiro; Giraldo, Paulo César; Gonçalves, Ana Katherine Silveira; Eleutério, Renata Mírian Nunes; Oliveira, Denise Nunes; Jacyntho, Cláudia

    2015-05-01

    Screening for anal cancer using cytology has not been considered in immunocompetent women. The aim of this study was to identify cytological atypia and human papillomavirus (HPV) DNA in intra-anal specimens from human immunodeficiency virus (HIV)-negative women with and without genital HPV lesions. This study was a cross-sectional analysis of 142 women who were negative for the HIV: 80 with genital lesions that were associated with HPV and 62 without HPV-induced lesions. The women were evaluated at the Federal University of Ceará from October 2011 to June 2012. The statistical analysis included the Fisher exact test and the odds ratio (CI 95%). Atypical anal cytology was observed in 24 (29.3%) patients in the study group and in 11 (17.8%) patients in the control group. In cases with at least two sites of HPV-associated lesions, 12 (41.4%) presented atypical cytology (P = 0.0220; OR = 2.7621, 1.1579-6.5889). When the practice of anal sex was evaluated, atypical cytology was observed in 22/43 (34%) [P = 0.0214; OR = 2.519, 1.146-5.534]. HPV DNA was detected in 17/27 (63%) cases with at least two sites of lesions (P = 0.0293, OR = 2.4855, 1.0960-5.6367). In the 33 cases who presented positive HPV DNA test results, the liquid-based cytology results were atypical (P = 0.0212, OR = 2.8, 1.1665-6.7208). Based on the results, liquid-based cytology may be used to detect intra-anal lesions, especially among women who have a history of anal intercourse or who have genital HPV-associated lesions at multiple sites. © 2014 Wiley Periodicals, Inc.

  13. Comparison of the clinical performances of the AdvanSure HPV Screening Real-Time PCR, the Abbott Real-Time High-Risk HPV Test, and the Hybrid Capture High-Risk HPV DNA Test for Cervical Cancer Screening.

    Science.gov (United States)

    Chung, Hae-Sun; Hahm, Chorong; Lee, Miae

    2014-09-01

    The clinical performance of three human papillomavirus (HPV) DNA commercial assays for cervical cancer screening was evaluated; the AdvanSure HPV Screening Real-Time PCR (AdvanSure PCR; LG Life Sciences) that was developed recently for the detection of both high-risk and low-risk genotypes, the Abbott RealTime High-Risk HPV Test (Abbott PCR; Abbott Molecular) and the Hybrid Capture High-Risk HPV DNA test (HC2; Qiagen). The three different HPV DNA tests were compared using cytology samples obtained from 619 women who underwent routine cervical cancer screening. The gold-standard assay was histopathological confirmation of cervical intraepithelial neoplasia of grade 2 or worse. The clinical sensitivities of the AdvanSure PCR, the Abbott PCR and the HC2 for the detection of cervical intraepithelial neoplasia of grade 2 or worse were 95.5%, 95.5% and 100%, respectively, while the clinical specificities were 61.6%, 86.4% and 83.3%, respectively. There were no significant differences in the clinical sensitivities of the Abbott PCR and the AdvanSure PCR compared to the HC2. The clinical specificities of the Abbott PCR and the AdvanSure PCR for the detection of HPV types 16/18 were 97.8% and 98.5%, respectively. For cervical cancer screening, all three tests showed relatively good clinical sensitivities, but the AdvanSure PCR had lower clinical specificity than the Abbott PCR and the HC2. The AdvanSure PCR and the Abbott PCR assays have the advantage of being automated and the ability to distinguish between HPV types 16/18 and other HPV types. The two real-time PCR assays could be useful tools in HPV testing for cervical cancer screening. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. The clinical utility of HPV DNA testing in cervical cancer screening strategies.

    Science.gov (United States)

    Bhatla, Neerja; Moda, Nidhi

    2009-09-01

    Cervical cancer continues to be the commonest cause of death among women in developing countries, largely due to the failure to the inability to sustain effective cytology-based screening programs. While this burden may come down following implementation of the human papillomavirus (HPV) vaccine, screening will still be required. HPV DNA testing is a promising new technology for cervical cancer prevention and is the most reproducible of all cervical cancer screening tests. Presently, the two assays most widely used for the detection of genital types are the polymerase chain reaction (PCR) and Hybrid Capture 2 assays (hc2). Rapid, affordable tests are expected to be available soon. HPV DNA testing can be used in a variety of clinical scenarios that include primary screening in women older than 30 yr; as an adjunctive test to cytology; in the triage of women with an equivocal cytologic report, e.g., ASC-US; or for follow-up post-treatment for cervical intraepithelial neoplasia (CIN). HPV DNA testing can also be performed on self-collected samples, which allows screening in remote areas and also in women who refuse gynecologic examination.

  15. Human immunodeficiency virus and human papilloma virus - why HPV-induced lesions do not spontaneously resolve and why therapeutic vaccination can be successful

    Directory of Open Access Journals (Sweden)

    van der Burg Sjoerd H

    2009-12-01

    Full Text Available Abstract HIV and HPV can both cause chronic infections and are acquired during sexual contact. HIV infection results in a progressive loss of CD4+ T cells that is associated with an increased prevalence of HPV infections, type-specific persistence and an increase in HPV-associated malignancies. On the one hand this illustrates the important role of HPV-specific CD4+ helper T-cell immunity, on the other it shows the Achilles heel of the HPV-specific immune response. The use of highly active antiretroviral therapy (HAART results in a rapid reduction of HIV and a reconstitution of systemic CD4+ T-cell levels. The use of HAART thus has the potential to raise immunity to HPV but to the surprise of many, the incidence of HPV-induced diseases has increased rather than declined since the introduction of HAART. Here, the knowledge on how HPV-induced diseases develop in the face of a non-compromised immune system will be used to explain why the effect of HAART on HPV-induced diseases is modest at best. Furthermore, exciting new data in the field of therapeutic vaccines against HPV will be discussed as this may form a more durable and clinically successful therapeutic approach for the treatment of HPV-induced high-grade lesions in HIV-positive subjects on HAART.

  16. [Health technology assessment report: HPV DNA based primary screening for cervical cancer precursors].

    Science.gov (United States)

    Ronco, Guglielmo; Biggeri, Annibale; Confortini, Massimo; Naldoni, Carlo; Segnan, Nereo; Sideri, Mario; Zappa, Marco; Zorzi, Manuel; Calvia, Maria; Accetta, Gabriele; Giordano, Livia; Cogo, Carla; Carozzi, Francesca; Gillio Tos, Anna; Arbyn, Marc; Mejier, Chris J L M; Snijders, Peter J F; Cuzick, Jack; Giorgi Rossi, Paolo

    2012-01-01

    OBJECTIVE OF THE PROJECT: The introduction of the HPV test as a primary screening test will cause important changes in the screening system based on cytology. The purposes of this report are: to define the best screening policies with HPV-based screening on the basis of the resulting efficacy and of undesired effects; comparing them to cytology-based screening; to identify their best conditions of application; to evaluate economic cost, feasibility and impact on the organisation of services of such policy in the Italian situation. This report contains a section on efficacy and undesired effects based on a systematic review of literature conducted in strict coordination with the preparation of a supplement to the European Guidelines for quality assurance in cervical cancer screening. This chapter corresponds to a preliminary version of the chapter of the European Guidelines on primary screening with HPV. The sections on costs, impact on organisation, and social, ethical and legal impact reflect the Italian situation; they are based on a review of the available Italian data (including unpublished data, mainly from on-going pilot projects) and on a structured analysis of what will result if the proposed protocol is applied to the Italian situation. Efficacy and undesired effects. There is clear scientific evidence that a screening based on validated tests for the DNA of oncogenic HPV as primary test and applying an appropriate protocol is more effective than screening based on cytology in preventing invasive cancers of the uterine cervix. In addition, it entails a limited--if any--increase of the undesired effects both in terms of unneeded referral to diagnostic work-up and in terms of over-diagnosis and consequent overtreatment of spontaneously regressive lesions. The crucial elements of such protocol are the followings: HPV-positive women are not to be directly referred to colposcopy, but the use of triage systems is essential. The currently recommendable method is

  17. Detection of HPV DNA and immunohistochemical expression of cell cycle proteins in oral carcinoma in a population of brazilian patients

    Directory of Open Access Journals (Sweden)

    Rosilene Calazans Soares

    2008-10-01

    Full Text Available This study investigated the presence of human papillomavirus (HPV DNA and viral types in 33 cases of oral squamous cells carcinoma (OSCC and compared the immunohistochemical expression of the cell-cycle markers p21 and pRb between cases of the disease with and without HPV. DNA was extracted from paraffin-embedded tissue and amplified by PCR for the detection of HPV DNA. Viral typing was performed by dot blot hybridization. Immunohistochemistry was performed by the streptavidinbiotin technique. HPV DNA was detected in 11 (33.33% of the 33 cases. The prevalent viral type was HPV 18 (81.81%. A significant association was observed between the presence of HPV and immunohistochemical expression of pRb, but not between p21 expression and the presence of the virus. The low frequency of detection of HPV DNA in OSCC suggests a possible participation of the virus in the development and progression of only a subgroup of these tumors.

  18. Implementing specificity of HPV-DNA primary screening in a successful organised cervical cancer prevention programme.

    Science.gov (United States)

    Zappacosta, Roberta; Caraceni, Donatella; Ciccocioppo, Lucia; Rotondo, Tiziana; Capanna, Serena; Gatta, Daniela Maria Pia; D'Angelo, Chiara; Rosini, Sandra

    2013-03-01

    This two-arm longitudinal study was performed within a regional organized cervical-cancer-prevention program in which HPV-DNA test is used in primary screening. The aim was to analyze the diagnostic performances of p16INK4a/Ki-67 dual-test and E6/E7-mRNA test in identifying CIN2+ lesion among HPV-DNA positive (HPV-DNAve) women triaged for LSIL-or-worse liquid based cytology (LBC). Thirty-six thousand thirty-one women participated to HPV-DNA screening program pilot study. Three thousand six hundred forty-one resulted HPV-DNAve; among these, 43% were LSIL-or-worse (LSIL+). HPV-DNAve/LSIL+ patients were submitted to colposcopy and histological assessment of any visible lesions. Dual-test was performed on 794 residual LBC specimens. In 405 cases, dual-test result was related to histology, considering CIN2+ as endpoint. mRNA test has been carried out retrospectively, on a subset of 173 residual LBC specimens. Agreement between dual-test and histological diagnosis was 59%. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of cytology-plus-dual-test approach were 62.3%, 76.8%, 63.1% and 84.2%, respectively. Dual-test improved specificity, PPV and NPV of cytological triage Agreement between mRNA testing and histology was 65%. Cytology-plus mRNA testing showing sensitivity, specificity, PPV and NPV reaching 32.1%, 94.9%, 75% and 50%, respectively; implemented specificity and PPV of cytology alone in triaging DNA-ve/LSIL+ patients (p<0.01). We provided promising data indicating the important role that p16(INK4)/Ki-67 dual-test, and mostly E6/E7 mRNA test, might have in triaging HPV-DNAve. These approaches would exclude the occurrence of cervical cancer and would avoid overtreatment, at the same time. Further longitudinal analysis has to be considered. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Sensitivity, Specificity, and Clinical Value of Human Papillomavirus (HPV) E6/E7 mRNA Assay as a Triage Test for Cervical Cytology and HPV DNA Test ▿

    Science.gov (United States)

    Benevolo, Maria; Vocaturo, Amina; Caraceni, Donatella; French, Deborah; Rosini, Sandra; Zappacosta, Roberta; Terrenato, Irene; Ciccocioppo, Lucia; Frega, Antonio; Rossi, Paolo Giorgi

    2011-01-01

    There is evidence that testing for human papillomavirus (HPV) E6/E7 mRNA is more specific than testing for HPV DNA. A retrospective study was carried out to evaluate the performance of the PreTect HPV-Proofer E6/E7 mRNA assay (Norchip) as a triage test for cytology and HPV DNA testing. This study analyzed 1,201 women, 688 of whom had a colposcopy follow-up and 195 of whom had histology-confirmed high-grade intraepithelial neoplasia or worse (CIN2+). The proportion of positive results and the sensitivity and specificity for CIN2+ were determined for HPV mRNA in comparison to HPV DNA and cytology. All data were adjusted for follow-up completeness. Stratified by cytological grades, the HPV mRNA sensitivity was 83% (95% confidence interval [CI] = 63 to 94%) in ASC-US (atypical squamous cells of undetermined significance), 62% (95% CI = 47 to 75%) in L-SIL (low-grade squamous intraepithelial lesion), and 67% (95% CI = 57 to 76%) in H-SIL (high-grade squamous intraepithelial lesion). The corresponding figures were 99, 91, and 96%, respectively, for HPV DNA. The specificities were 82, 76, and 45%, respectively, for HPV mRNA and 29, 13, and 4%, respectively, for HPV DNA. Used as a triage test for ASC-US and L-SIL, mRNA reduced colposcopies by 79% (95% CI = 74 to 83%) and 69% (95% CI = 65 to 74%), respectively, while HPV DNA reduced colposcopies by 38% (95% CI = 32 to 44%) and by 15% (95% CI = 12 to 19%), respectively. As a HPV DNA positivity triage test, mRNA reduced colposcopies by 63% (95% CI = 60 to 66%), having 68% sensitivity (95% CI = 61 to 75%), whereas cytology at the ASC-US+ threshold reduced colposcopies by 23% (95% CI = 20 to 26%), showing 92% sensitivity (95% CI = 87 to 95%). In conclusion, PreTect HPV-Proofer mRNA can serve as a better triage test than HPV DNA to reduce colposcopy referral in both ASC-US and L-SIL. It is also more efficient than cytology for the triage of HPV DNA-positive women. Nevertheless, its low sensitivity demands a strict follow-up of

  20. Presence of high risk HPV DNA but indolent transcription of E6/E7 oncogenes in invasive ductal carcinoma of breast.

    Science.gov (United States)

    Wang, Depu; Fu, Ling; Shah, Walayat; Zhang, Jingwen; Yan, Yan; Ge, Xinhong; He, Jianjun; Wang, Yili; Li, Xu

    2016-12-01

    The causative role of high risk human papillomavirus (HR-HPV) in breast cancer development is controversial, though a number of reports have identified HR-HPV DNA in breast cancer specimens. Nevertheless, most studies to date have focused primarily on viral DNA rather than the viral transcription. The aim of this study was to investigate the presence of HR-HPV in breast cancer tissues at HPV DNA level and HPV oncogenes mRNA level by in situ hybridization (ISH). One hundred and forty six (146) cases of breast invasive ductal carcinoma(IDC) and 83 cases of benign breast lesions were included in the study. Type specific oligonucleotide probes were used for the DNA detection of HPV 16,18 and 58 by ISH. HR-HPV oncogenes mRNA was assayed by novel RNAscope HR-HPV HR7 assay ISH. p16 protein expression was evaluated by immunohistochemistry (IHC). HR-HPV 16,18 and 58 DNA were detected in 52 out of 146 (35.6%) IDC and in 3 out of 83 (3.6%) benign breast lesions by ISH. The HR-HPV mRNAs was detected only in a few specimens with strong HPV DNA positivity(4/25) in a few scattered cancer cells with very weak punctate nuclear and/or cytoplasmic staining. p16 over-expression did not correlate with the HPV DNA positive breast cancer samples(17/52 HPVDNA+ vs 28/94 HPV DNA-, p=0.731). HR-HPVs certainly exist in breast cancer tissue with less active transcription, which implies that the causal role of HPV in breast cancer development need further study. Copyright © 2016 Elsevier GmbH. All rights reserved.

  1. Comparison of the detection of HPV-16, 18, 31, 33, and 45 by type-specific DNA- and E6/E7 mRNA-based assays of HPV DNA positive women with abnormal Pap smears.

    Science.gov (United States)

    Salimović-Bešić, Irma; Tomić-Čiča, Anja; Smailji, Admir; Hukić, Mirsada

    2013-12-01

    This study compares the type-specific human papillomavirus (HPV) DNA test with E6/E7 mRNA detection assay because of their importance in cervical cancer screening programs. A total of 105 women with positive high-risk Hybrid Capture 2 or Abbott RealTime High Risk HPV screening test and an abnormal cervical Pap smear were enrolled in the study. HPV typing was performed by multiplex real-time PCR (HPV High Risk Typing Real-TM test). HPV-16, 18, 31, 33, and 45 E6/E7 mRNAs were determined by type-specific real-time NASBA assay (NucliSENS EasyQ HPV v1.1). Infections caused by HPV-16, 18, 31, 33, and 45 types increased with severity of cervical cytology (p=0.008). Global positivity of five HPV E6/E7 mRNAs was lower than DNA positivity within women with atypical squamous cells of undetermined significance (p=0.016; p=0.008). High agreement of the tests was found in the groups of women with low-grade (p=1.000; p=0.063) and high-grade squamous intraepithelial lesion (p=0.250; p=0.125). Type-specific agreement of both diagnostic approaches was high regardless of cytology. Based on the found differences between HPV-16, 18, 31, 33, and 45 E6/E7 mRNA and DNA positivity, further study is needed to test the role of mRNA testing in the triage of women with atypical squamous cells of undetermined significance in Pap smear. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Comparison of HPV DNA testing in cervical exfoliated cells and tissue biopsies among HIV-positive women in Kenya.

    Science.gov (United States)

    De Vuyst, Hugo; Chung, Michael H; Baussano, Iacopo; Mugo, Nelly R; Tenet, Vanessa; van Kemenade, Folkert J; Rana, Farzana S; Sakr, Samah R; Meijer, Chris J L M; Snijders, Peter J F; Franceschi, Silvia

    2013-09-15

    HIV-positive women are infected with human papillomavirus (HPV) (especially with multiple types), and develop cervical intraepithelial neoplasia (CIN) and cervical cancer more frequently than HIV-negative women. We compared HPV DNA prevalence obtained using a GP5+/6+ PCR assay in cervical exfoliated cells to that in biopsies among 468 HIV-positive women from Nairobi, Kenya. HPV prevalence was higher in cells than biopsies and the difference was greatest in 94 women with a combination normal cytology/normal biopsy (prevalence ratio, PR = 3.7; 95% confidence interval, CI: 2.4-5.7). PR diminished with the increase in lesion severity (PR in 58 women with high-grade squamous intraepithelial lesions (HSIL)/CIN2-3 = 1.1; 95% CI: 1.0-1.2). When HPV-positive, cells contained 2.0- to 4.6-fold more multiple infections than biopsies. Complete or partial agreement between cells and biopsies in the detection of individual HPV types was found in 91% of double HPV-positive pairs. The attribution of CIN2/3 to HPV16 and/or 18 would decrease from 37.6%, when the presence of these types in either cells or biopsies was counted, to 20.2% when it was based on the presence of HPV16 and/or 18 (and no other types) in biopsies. In conclusion, testing HPV on biopsies instead of cells results in decreased detection but not elimination of multiple infections in HIV-positive women. The proportion of CIN2/3 attributable to HPV16 and/or 18 among HIV-positive women, which already appeared to be lower than that in HIV-negative, would then further decrease. The meaning of HPV detection in cells and random biopsy from HIV-positive women with no cervical abnormalities remains unclear. Copyright © 2013 UICC.

  3. DNA damage repair genes controlling human papillomavirus (HPV episome levels under conditions of stability and extreme instability.

    Directory of Open Access Journals (Sweden)

    Terri G Edwards

    Full Text Available DNA damage response (DDR genes and pathways controlling the stability of HPV episomal DNA are reported here. We set out to understand the mechanism by which a DNA-binding, N-methylpyrrole-imidazole hairpin polyamide (PA25 acts to cause the dramatic loss of HPV DNA from cells. Southern blots revealed that PA25 alters HPV episomes within 5 hours of treatment. Gene expression arrays identified numerous DDR genes that were specifically altered in HPV16 episome-containing cells (W12E by PA25, but not in HPV-negative (C33A cells or in cells with integrated HPV16 (SiHa. A siRNA screen of 240 DDR genes was then conducted to identify enhancers and repressors of PA25 activity. Serendipitously, the screen also identified many novel genes, such as TDP1 and TDP2, regulating normal HPV episome stability. MRN and 9-1-1 complexes emerged as important for PA25-mediated episome destruction and were selected for follow-up studies. Mre11, along with other homologous recombination and dsDNA break repair genes, was among the highly significant PA25 repressors. The Mre11 inhibitor Mirin was found to sensitize HPV episomes to PA25 resulting in a ∼5-fold reduction of the PA25 IC50. A novel assay that couples end-labeling of DNA to Q-PCR showed that PA25 causes strand breaks within HPV DNA, and that Mirin greatly enhances this activity. The 9-1-1 complex member Rad9, a representative PA25 enhancer, was transiently phosphorylated in response to PA25 treatment suggesting that it has a role in detecting and signaling episome damage by PA25 to the cell. These results establish that DNA-targeted compounds enter cells and specifically target the HPV episome. This action leads to the activation of numerous DDR pathways and the massive elimination of episomal DNA from cells. Our findings demonstrate that viral episomes can be targeted for elimination from cells by minor groove binding agents, and implicate DDR pathways as important mediators of this process.

  4. DNA damage repair genes controlling human papillomavirus (HPV) episome levels under conditions of stability and extreme instability.

    Science.gov (United States)

    Edwards, Terri G; Vidmar, Thomas J; Koeller, Kevin; Bashkin, James K; Fisher, Chris

    2013-01-01

    DNA damage response (DDR) genes and pathways controlling the stability of HPV episomal DNA are reported here. We set out to understand the mechanism by which a DNA-binding, N-methylpyrrole-imidazole hairpin polyamide (PA25) acts to cause the dramatic loss of HPV DNA from cells. Southern blots revealed that PA25 alters HPV episomes within 5 hours of treatment. Gene expression arrays identified numerous DDR genes that were specifically altered in HPV16 episome-containing cells (W12E) by PA25, but not in HPV-negative (C33A) cells or in cells with integrated HPV16 (SiHa). A siRNA screen of 240 DDR genes was then conducted to identify enhancers and repressors of PA25 activity. Serendipitously, the screen also identified many novel genes, such as TDP1 and TDP2, regulating normal HPV episome stability. MRN and 9-1-1 complexes emerged as important for PA25-mediated episome destruction and were selected for follow-up studies. Mre11, along with other homologous recombination and dsDNA break repair genes, was among the highly significant PA25 repressors. The Mre11 inhibitor Mirin was found to sensitize HPV episomes to PA25 resulting in a ∼5-fold reduction of the PA25 IC50. A novel assay that couples end-labeling of DNA to Q-PCR showed that PA25 causes strand breaks within HPV DNA, and that Mirin greatly enhances this activity. The 9-1-1 complex member Rad9, a representative PA25 enhancer, was transiently phosphorylated in response to PA25 treatment suggesting that it has a role in detecting and signaling episome damage by PA25 to the cell. These results establish that DNA-targeted compounds enter cells and specifically target the HPV episome. This action leads to the activation of numerous DDR pathways and the massive elimination of episomal DNA from cells. Our findings demonstrate that viral episomes can be targeted for elimination from cells by minor groove binding agents, and implicate DDR pathways as important mediators of this process.

  5. Comparison of Onclarity Human Papillomavirus (HPV) Assay with Hybrid Capture II HPV DNA Assay for Detection of Cervical Intraepithelial Neoplasia Grade 2 and 3 Lesions.

    Science.gov (United States)

    Bottari, F; Sideri, M; Gulmini, C; Igidbashian, S; Tricca, A; Casadio, C; Carinelli, S; Boveri, S; Ejegod, D; Bonde, J; Sandri, M T

    2015-07-01

    Analytical and clinical performance validation is essential before introduction of a new human papillomavirus (HPV) assay into clinical practice. This study compares the new BD Onclarity HPV assay, which detects E6/E7 DNA from 14 high-risk HPV types, to the Hybrid Capture II (HC2) HPV DNA test, to concurrent cytology and histology results, in order to evaluate its performance in detecting high-grade cervical lesions. A population of 567 women, including 325 with ≥ASCUS (where ASCUS stands for atypical cells of undetermined significance) and any HC2 result and 242 with both negative cytology and negative HC2 results, were prospectively enrolled for the study. The overall agreement between Onclarity and HC2 was 94.6% (95% confidence intervals [CI], 92.3% to 96.2%). In this population with a high prevalence of disease, the relative sensitivities (versus adjudicated cervical intraepithelial neoplasia grades 2 and 3 [CIN2+] histology endpoints) of the Onclarity and HC2 tests were 95.2% (95% CI, 90.7% to 97.5%) and 96.9% (95% CI, 92.9% to 98.7%), respectively, and the relative specificities were 50.3% (95% CI, 43.2% to 57.4%) for BD and 40.8% (95% CI, 33.9%, 48.1%) for HC2. These results indicate that the BD Onclarity HPV assay has sensitivity comparable to that of the HC2 assay, with a trend to an increased specificity. Moreover, as Onclarity gives the chance to discriminate between the different genotypes, we calculated the genotype prevalence and the absolute risk of CIN2+: HPV 16 was the most prevalent genotype (19.8%) with an absolute risk of CIN2+ of 77.1%. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  6. HPV vaccine

    Science.gov (United States)

    Vaccine - HPV; Immunization - HPV; Gardasil; HPV2; HPV4; Vaccine to prevent cervical cancer; Genital warts - HPV vaccine; Cervical dysplasia - HPV vaccine; Cervical cancer - HPV vaccine; Cancer of the cervix - HPV vaccine; Abnormal ...

  7. Inhibiting DNA Polymerases as a Therapeutic Intervention against Cancer

    Directory of Open Access Journals (Sweden)

    Anthony J. Berdis

    2017-11-01

    Full Text Available Inhibiting DNA synthesis is an important therapeutic strategy that is widely used to treat a number of hyperproliferative diseases including viral infections, autoimmune disorders, and cancer. This chapter describes two major categories of therapeutic agents used to inhibit DNA synthesis. The first category includes purine and pyrmidine nucleoside analogs that directly inhibit DNA polymerase activity. The second category includes DNA damaging agents including cisplatin and chlorambucil that modify the composition and structure of the nucleic acid substrate to indirectly inhibit DNA synthesis. Special emphasis is placed on describing the molecular mechanisms of these inhibitory effects against chromosomal and mitochondrial DNA polymerases. Discussions are also provided on the mechanisms associated with resistance to these therapeutic agents. A primary focus is toward understanding the roles of specialized DNA polymerases that by-pass DNA lesions produced by DNA damaging agents. Finally, a section is provided that describes emerging areas in developing new therapeutic strategies targeting specialized DNA polymerases.

  8. Two novel genital human papillomavirus (HPV) types, HPV68 and HPV70, related to the potentially oncogenic HPV39.

    OpenAIRE

    Longuet, M; Beaudenon, S; Orth, G

    1996-01-01

    The genomes of two novel human papillomavirus (HPV) types, HPV68 and HPV70, were cloned from a low-grade cervical intraepithelial neoplasia and a vulvar papilloma, respectively, and partially sequenced. Both types are related to HPV39, a potentially oncogenic virus. HPV68 and HPV70 were also detected in genital intraepithelial neoplasia from three patients and one patient, respectively. Comparison with sequence data in the literature indicates that the subgenomic ME180-HPV DNA fragment, clone...

  9. Use of cell-SELEX to generate DNA aptamers as molecular probes of HPV-associated cervical cancer cells.

    Directory of Open Access Journals (Sweden)

    Jessica C Graham

    Full Text Available Disease-specific biomarkers are an important tool for the timely and effective management of pathological conditions, including determination of susceptibility, diagnosis, and monitoring efficacy of preventive or therapeutic strategies. Aptamers, comprising single-stranded or double-stranded DNA or RNA, can serve as biomarkers of disease or biological states. Aptamers can bind to specific epitopes on macromolecules by virtue of their three dimensional structures and, much like antibodies, aptamers can be used to target specific epitopes on the basis of their molecular shape. The Systematic Evolution of Ligands by EXponential enrichment (SELEX is the approach used to select high affinity aptamers for specific macromolecular targets from among the >10(13 oligomers comprising typical random oligomer libraries. In the present study, we used live cell-based SELEX to identify DNA aptamers which recognize cell surface differences between HPV-transformed cervical carcinoma cancer cells and isogenic, nontumorigenic, revertant cell lines.Whole-cell SELEX methodology was adapted for use with adherent cell lines (which we termed Adherent Cell-SELEX (AC-SELEX. Using this approach, we identified high affinity aptamers (nanomolar range K(d to epitopes specific to the cell surface of two nontumorigenic, nontumorigenic revertants derived from the human cervical cancer HeLa cell line, and demonstrated the loss of these epitopes in another human papillomavirus transformed cervical cancer cell line (SiHa. We also performed preliminary investigation of the aptamer epitopes and their binding characteristics.Using AC-SELEX we have generated several aptamers that have high affinity and specificity to the nontumorigenic, revertant of HPV-transformed cervical cancer cells. These aptamers can be used to identify new biomarkers that are related to carcinogenesis. Panels of aptamers, such as these may be useful in predicting the tumorigenic potential and properties of

  10. Human Papillomavirus (HPV) Infection in Squamous Cell Carcinomas Arising From the Oropharynx: Detection of HPV DNA and p16 Immunohistochemistry as Diagnostic and Prognostic Indicators—A Pilot Study

    Energy Technology Data Exchange (ETDEWEB)

    Bussu, Francesco, E-mail: francesco.bussu.md@gmail.com [Institute of Otolaryngology, Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, Roma (Italy); Sali, Michela [Institute of Microbiology, Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, Roma (Italy); Gallus, Roberto [Institute of Otolaryngology, Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, Roma (Italy); Petrone, Gianluigi; Zannoni, Gian Franco [Institute of Histopathology, Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, Roma (Italy); Autorino, Rosa; Dinapoli, Nicola [Institute of Radiotherapy, Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, Roma (Italy); Santangelo, Rosaria [Institute of Microbiology, Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, Roma (Italy); Vellone, Valerio Gaetano [Institute of Histopathology, Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, Roma (Italy); Graziani, Cristina [Institute of Otolaryngology, Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, Roma (Italy); Miccichè, Francesco [Institute of Radiotherapy, Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, Roma (Italy); Almadori, Giovanni; Galli, Jacopo [Institute of Otolaryngology, Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, Roma (Italy); Delogu, Giovanni; Sanguinetti, Maurizio [Institute of Microbiology, Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, Roma (Italy); Rindi, Guido [Institute of Histopathology, Università Cattolica del Sacro Cuore, Policlinico A. Gemelli, Roma (Italy); and others

    2014-08-01

    Purpose: Human papillomavirus (HPV) 16 infection is associated with oropharyngeal carcinogenesis and is likely the cause of the reported increase in disease incidence. We evaluated the prevalence of HPV infection and the reliability of different diagnostic tools using primary tumor samples from a cohort of 50 patients. Methods and Materials: Formalin-fixed paraffin-embedded (FFPE) tumor samples were collected from all 50 consecutive primary oropharyngeal SCC patients who were enrolled in the study; fresh tumor samples were available in 22 cases. NucliSENS EasyQ HPVv1 was used for RNA, and Digene Hybrid Capture-2(HC2) was used for DNA detection. p16 Expression was evaluated by immunohistochemistry in FPPE specimens. Results: Based on the DNA detection assay on FFPE samples, the frequency of high-risk HPV infection was 32%. The agreement rate between HPV RNA and HPV DNA detection in fresh samples was 100%. The agreement rate between p16 immunohistochemistry (IHC) and the detection of HPV DNA in the FFPE samples was fair but not excellent (κ = 0.618). HPV DNA detection was highly significant, as measured by disease-specific survival and determined using a Wilcoxon test (P=.001). p16 IHC also exhibited a prognostic value but with a lower statistical significance (P=.0475). The detection of HPV DNA, but not p16 IHC, was also significantly correlated with locoregional control (P=.0461). Conclusion: Diagnostic methods based on the detection of HPV nucleic acids appear to be more reliable and objective because they do not require reading by a trained histopathologist. Furthermore, the detection of HPV DNA exhibits an improved correlation with survival, and therefore appears definitely more reliable than p16 IHC for routine use in clinical practice.

  11. Mitochondrial DNA ancestry, HPV infection and the risk of cervical cancer in a multiethnic population of northeastern Argentina.

    Directory of Open Access Journals (Sweden)

    Ines Badano

    Full Text Available Misiones Province in northeastern Argentina is considered to be a region with a high prevalence of HPV infection and a high mortality rate due to cervical cancer. The reasons for this epidemiological trend are not completely understood. To gain insight into this problem, we explored the relationship between mitochondrial DNA (mtDNA ancestry, HPV infection, and development of cervical lesions/cancer in women from the city of Posadas in Misiones Province.Two hundred and sixty-one women, including 92 cases of patients diagnosed with cervical lesions and 169 controls, were analyzed. mtDNA ancestry was assessed through HVS1 sequencing, while the detection and typing of HPV infection was conducted through nested multiplex PCR analysis. Multivariate logistic regression was conducted with the resulting data to estimate the odds ratios (ORs adjusted by socio-demographic variables.The study participants showed 68.6% Amerindian, 26.1% European and 5.3% African mtDNA ancestry, respectively. Multiple regression analysis showed that women with African mtDNAs were three times more likely to develop a cervical lesion than those with Native American or European mtDNAs [OR of 3.8 (1.2-11.5 for ancestry and OR of 3.5 (1.0-12.0 for L haplogroups], although the associated p values were not significant when tested under more complex multivariate models. HPV infection and the development of cervical lesions/cancer were significant for all tested models, with the highest OR values for HPV16 [OR of 24.2 (9.3-62.7] and HPV-58 [OR of 19.0 (2.4-147.7].HPV infection remains a central risk factor for cervical cancer in the Posadas population. The potential role of African mtDNA ancestry opens a new avenue for future medical association studies in multiethnic populations, and will require further confirmation in large-scale studies.

  12. Mitochondrial DNA ancestry, HPV infection and the risk of cervical cancer in a multiethnic population of northeastern Argentina.

    Science.gov (United States)

    Badano, Ines; Sanabria, Daiana J; Totaro, Maria E; Rubinstein, Samara; Gili, Juan A; Liotta, Domingo J; Picconi, Maria A; Campos, Rodolfo H; Schurr, Theodore G

    2018-01-01

    Misiones Province in northeastern Argentina is considered to be a region with a high prevalence of HPV infection and a high mortality rate due to cervical cancer. The reasons for this epidemiological trend are not completely understood. To gain insight into this problem, we explored the relationship between mitochondrial DNA (mtDNA) ancestry, HPV infection, and development of cervical lesions/cancer in women from the city of Posadas in Misiones Province. Two hundred and sixty-one women, including 92 cases of patients diagnosed with cervical lesions and 169 controls, were analyzed. mtDNA ancestry was assessed through HVS1 sequencing, while the detection and typing of HPV infection was conducted through nested multiplex PCR analysis. Multivariate logistic regression was conducted with the resulting data to estimate the odds ratios (ORs) adjusted by socio-demographic variables. The study participants showed 68.6% Amerindian, 26.1% European and 5.3% African mtDNA ancestry, respectively. Multiple regression analysis showed that women with African mtDNAs were three times more likely to develop a cervical lesion than those with Native American or European mtDNAs [OR of 3.8 (1.2-11.5) for ancestry and OR of 3.5 (1.0-12.0) for L haplogroups], although the associated p values were not significant when tested under more complex multivariate models. HPV infection and the development of cervical lesions/cancer were significant for all tested models, with the highest OR values for HPV16 [OR of 24.2 (9.3-62.7)] and HPV-58 [OR of 19.0 (2.4-147.7)]. HPV infection remains a central risk factor for cervical cancer in the Posadas population. The potential role of African mtDNA ancestry opens a new avenue for future medical association studies in multiethnic populations, and will require further confirmation in large-scale studies.

  13. Randomized Controlled Trial of an Adjuvanted Human Papillomavirus (HPV) Type 6 L2E7 Vaccine: Infection of External Anogenital Warts with Multiple HPV Types and Failure of Therapeutic Vaccination

    National Research Council Canada - National Science Library

    Pierre Vandepapelière; Renzo Barrasso; Chris J. L. M. Meijer; Jan M. M. Walboomers; Martine Wettendorff; Lawrence R. Stanberry; Charles J. N. Lacey

    2005-01-01

    ...) type 6 or 11, supporting the concept of therapeutic vaccination. A therapeutic vaccine composed of HPV-6 L2E7 fusion protein and AS02A adjuvant was evaluated in conjunction with conventional therapies in subjects with anogenital warts. Methods...

  14. Zinc finger arrays binding human papillomavirus types 16 and 18 genomic DNA: precursors of gene-therapeutics for in-situ reversal of associated cervical neoplasia

    Directory of Open Access Journals (Sweden)

    Wayengera Misaki

    2012-07-01

    Full Text Available Abstract Background Human papillomavirus (HPV types 16 and 18 are the high-risk, sexually transmitted infectious causes of most cervical intraepithelial neoplasias (CIN or cancers. While efficacious vaccines to reduce the sexual acquisition of these high-risk HPVs have recently been introduced, no virus-targeted therapies exist for those already exposed and infected. Considering the oncogenic role of the transforming (E6 and E7 genes of high-risk HPVs in the slow pathogenesis of cervical cancer, we hypothesize that timely disruption or abolition of HPV genome expression within pre-cancerous lesions identified at screening may reverse neoplasia. We aimed to derive model zinc finger nucleases (ZFNs for mutagenesis of the genomes of two high-risk HPV (types 16 & 18. Methods and results Using ZiFiT software and the complete genomes of HPV types16 and 18, we computationally generated the consensus amino acid sequences of the DNA-binding domains (F1, F2, & F3 of (i 296 & 327 contextually unpaired (or single three zinc-finger arrays (sZFAs and (ii 9 & 13 contextually paired (left and right three- zinc-finger arrays (pZFAs that bind genomic DNA of HPV-types 16 and 18 respectively, inclusive of the E7 gene (s/pZFAHpV/E7. In the absence of contextually paired three-zinc-finger arrays (pZFAs that bind DNA corresponding to the genomic context of the E6 gene of either HPV type, we derived the DNA binding domains of another set of 9 & 14 contextually unpaired E6 gene-binding ZFAs (sZFAE6 to aid the future quest for paired ZFAs to target E6 gene sequences in both HPV types studied (pZFAE6. This paper presents models for (i synthesis of hybrid ZFNs that cleave within the genomic DNA of either HPV type, by linking the gene sequences of the DNA-cleavage domain of the FokI endonuclease FN to the gene sequences of a member of the paired-HPV-binding ZFAs (pZFAHpV/E7 + FN, and (ii delivery of the same into precancerous lesions using HPV-derived viral plasmids or

  15. Comparison of the clinical performance of an HPV mRNA test and an HPV DNA test in triage of atypical squamous cells of undetermined significance (ASC-US)

    DEFF Research Database (Denmark)

    Waldstrom, M; Ornskov, D

    2012-01-01

    The effect of triaging women with atypical squamous cells of undetermined significance (ASC-US) with human papillomavirus (HPV) DNA testing has been well documented. New tests detecting HPV E6/E7 mRNA are emerging, claiming to be more specific for detecting high-grade disease. We evaluated...

  16. Ricerca di HPV-DNA e tipizzazione virale nella diagnostica di prevenzione del carcinoma della cervice uterina

    Directory of Open Access Journals (Sweden)

    Mauro Carcheri

    2003-03-01

    Full Text Available Papillomaviruses are relatively ubiquitous and have been described as causative agents for epithelial lesions in a wide variety of animals as well as in humans. Approximately 30 HPV types have been isolated from anogenital epithelium (cervix, vagina, vulva, rectum and penis. HPVs induce a variety of proliferative lesions, but only the “high-risk” types are associated with anogenital cancers. “Low-risk” viral types include HPV-6 and HPV-11; “high-risk” types include HPV-16, 18, 31 and 56. HPVs “high-risk” types are more strongly associated with high-grade lesions (HSIL than they are with low-grade lesions (LSIL. The traditional process for cervical cancer screening programs (PAP test is vulnerable to air drying artifacts and has limits to sensitivity, since as many as 90 percent of collectet cells can be discarted with collection device. The present study was undertaken to assess the screening performance of HPV-DNA typing in a sample of 142 women drawn from a routine screening for the prevention of cervical cancer. The results indicate that HPV-DNA screening and typing, used together with PAP test, can improve the detection of patients with cervical disease and can serve as a quality assurance indicator in cervical cancer screening programs.

  17. DNA vaccine encoding HPV-16 E7 with mutation in L-Y-C-Y-E pRb-binding motif induces potent anti-tumor responses in mice.

    Science.gov (United States)

    Bahrami, Armina Alagheband; Ghaemi, Amir; Tabarraei, Alijan; Sajadian, Azadeh; Gorji, Ali; Soleimanjahi, Hoorieh

    2014-09-01

    Cervical cancer is the second most common cancer among women worldwide and remains a clinical problem despite improvements in early detection and therapy. The human papillomavirus (HPV) type 16 (HPV16) E7 oncoprotein expressed in cervical carcinoma cells are considered as attractive tumor-specific antigen targets for immunotherapy. Since the transformation potential of the oncogenes, vaccination based of these oncogenes is not safe. In present study, DNA vaccine expressing the modified variant with mutation in pRb-binding motif of the HPV-16 E7 oncoprotein was generated. A novel modified E7 gene with mutation in LYCYE motif was designed and constructed and the immunogenicity and antitumor effect of therapeutic DNA vaccines encoding the mutant and wild type of E7 gene were investigated. The L-Y-C-Y-E pRb-binding motif of E7 proteins has been involved in the immortalization and transformation of the host cell. The results showed that the mutant and wild type HPV-16 E7 vectors expressed the desired protein. Furthermore, the immunological mechanism behind mutant E7 DNA vaccine can be attributed at least partially to increased cytotoxic T lymphocyte, accompanied by the up-regulation of Th1-cytokine IFN-γ and TNF-β and down-regulation of Th3-cytokine TGF-β. Immunized mice with mutant plasmid demonstrated significantly stronger cell immune responses and higher levels of tumor protection than wild-type E7 DNA vaccine. The results exhibit that modified E7 DNA vaccine may be a promising candidate for development of therapeutic vaccine against HPV-16 cancers. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Comparison of Real-Time Multiplex Human Papillomavirus (HPV) PCR Assays with INNO-LiPA HPV Genotyping Extra Assay▿

    OpenAIRE

    Else, Elizabeth A.; Swoyer, Ryan; Zhang, Yuhua; Taddeo, Frank J; Bryan, Janine T.; Lawson, John; Van Hyfte, Inez; Roberts, Christine C.

    2011-01-01

    Real-time type-specific multiplex human papillomavirus (HPV) PCR assays were developed to detect HPV DNA in samples collected for the efficacy determination of the quadrivalent HPV (type 6, 11, 16, and 18) L1 virus-like particle (VLP) vaccine (Gardasil). Additional multiplex (L1, E6, and E7 open reading frame [ORF]) or duplex (E6 and E7 ORF) HPV PCR assays were developed to detect high-risk HPV types, including HPV type 31 (HPV31), HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58, and H...

  19. Antitumor HPV E7-specific CTL activity elicited by in vivo engineered exosomes produced through DNA inoculation.

    Science.gov (United States)

    Di Bonito, Paola; Chiozzini, Chiara; Arenaccio, Claudia; Anticoli, Simona; Manfredi, Francesco; Olivetta, Eleonora; Ferrantelli, Flavia; Falcone, Emiliana; Ruggieri, Anna; Federico, Maurizio

    2017-01-01

    We recently proved that exosomes engineered in vitro to deliver high amounts of HPV E7 upon fusion with the Nef(mut) exosome-anchoring protein elicit an efficient anti-E7 cytotoxic T lymphocyte immune response. However, in view of a potential clinic application of this finding, our exosome-based immunization strategy was faced with possible technical difficulties including industrial manufacturing, cost of production, and storage. To overcome these hurdles, we designed an as yet unproven exosome-based immunization strategy relying on delivery by intramuscular inoculation of a DNA vector expressing Nef(mut) fused with HPV E7. In this way, we predicted that the expression of the Nef(mut)/E7 vector in muscle cells would result in a continuous source of endogenous (ie, produced by the inoculated host) engineered exosomes able to induce an E7-specific immune response. To assess this hypothesis, we first demonstrated that the injection of a Nef(mut)/green fluorescent protein-expressing vector led to the release of fluorescent exosomes, as detected in plasma of inoculated mice. Then, we observed that mice inoculated intramuscularly with a vector expressing Nef(mut)/E7 developed a CD8(+) T-cell immune response against both Nef and E7. Conversely, no CD8(+) T-cell responses were detected upon injection of vectors expressing either the wild-type Nef isoform of E7 alone, most likely a consequence of their inefficient exosome incorporation. The production of immunogenic exosomes in the DNA-injected mice was formally demonstrated by the E7-specific CD8(+) T-cell immune response we detected in mice inoculated with exosomes isolated from plasma of mice inoculated with the Nef(mut)/E7 vector. Finally, we provide evidence that the injection of Nef(mut)/E7 DNA led to the generation of effective antigen-specific cytotoxic T lymphocytes whose activity was likely part of the potent, therapeutic antitumor effect we observed in mice implanted with TC-1 tumor cells. In summary, we

  20. Recombined DNA vaccines encoding calreticulin linked to HPV6bE7 enhance immune response and inhibit angiogenic activity in B16 melanoma mouse model expressing HPV 6bE7 antigen.

    Science.gov (United States)

    Zhao, Ke-Jia; Cheng, Hao; Zhu, Ke-Jian; Xu, Yan; Chen, Min-Li; Zhang, Xing; Song, Tao; Ye, Jun; Wang, Qi; Chen, Da-Fang

    2006-07-01

    Calreticulin (CRT) has been reported to have an effect of upregulating MHC class I presentation as well as inhibiting angiogenesis in vitro and in vivo. Combination of dual mechanisms of enhanced immunogenicity of human papillomavirus (HPV) 6bE7 antigen and antiangiogenesis may be introduced in the strategy of vaccines against condyloma acuminatum (CA) resulting from HPV infection. Therefore, we constructed DNA vaccines by employing different lengths of CRT chimerically linked to a model antigen HPV6bE7 and investigated the immunological and antiangiogenic effects of these vaccines in a B16 melanoma model that express HPV6bE7 antigen. Our results showed that vaccination with CRT180/HPV6bE7 or CRT120/HPV6bE7 enhanced the presence of CD8(+) T cells and TCRgammadelta T cells in vivo, increased the specific lysis activity against E7-expressing cells and secretion levels of IL-2 and IFN-gamma by activating T cells in vitro significantly. Moreover, recombined CRT180 or CRT120 with HPV6bE7 vaccines could elicit a more efficient E7-specific immune response than HPV6bE7 alone. The similarity of immunological enhancement of CRT180/HPV6bE7 and CRT120/HPV6bE7 implies that the immunologically active region mainly exist in fragment 1-120 aa. Furthermore, CRT180/HPV6bE7 and CRT180 displayed remarkable superiority over CRT120/HPV6bE7 in vivo angiogenesis assay, suggesting that the antiangiogenic activity of CRT resides in a domain between aa 120 and 180. Vaccination with CRT180/HPV6bE7 generated the best protective effect of delaying tumor formation and reduction of tumor size in tumor growth inhibition experiment among all DNA constructs. Therefore, CRT180/HPV6bE7 vaccine may enhance the immunological response to HPV6bE7 and inhibit angiogenesis. This construct may be useful in preventing HPV-associated dermatosis and may be developed as a promising strategy to control CA.

  1. Photon-induced cell migration and integrin expression promoted by DNA integration of HPV16 genome

    Energy Technology Data Exchange (ETDEWEB)

    Rieken, Stefan; Simon, Florian; Habermehl, Daniel; Dittmar, Jan Oliver; Combs, Stephanie E.; Weber, Klaus; Debus, Juergen; Lindel, Katja [University Hospital of Heidelberg, Department of Radiation Therapy and Radiation Oncology, Heidelberg (Germany)

    2014-10-15

    Persistent human papilloma virus 16 (HPV16) infections are a major cause of cervical cancer. The integration of the viral DNA into the host genome causes E2 gene disruption which prevents apoptosis and increases host cell motility. In cervical cancer patients, survival is limited by local infiltration and systemic dissemination. Surgical control rates are poor in cases of parametrial infiltration. In these patients, radiotherapy (RT) is administered to enhance local control. However, photon irradiation itself has been reported to increase cell motility. In cases of E2-disrupted cervical cancers, this phenomenon would impose an additional risk of enhanced tumor cell motility. Here, we analyze mechanisms underlying photon-increased migration in keratinocytes with differential E2 gene status. Isogenic W12 (intact E2 gene status) and S12 (disrupted E2 gene status) keratinocytes were analyzed in fibronectin-based and serum-stimulated migration experiments following single photon doses of 0, 2, and 10 Gy. Quantitative FACS analyses of integrin expression were performed. Migration and adhesion are increased in E2 gene-disrupted keratinocytes. E2 gene disruption promotes attractability by serum components, therefore, effectuating the risk of local infiltration and systemic dissemination. In S12 cells, migration is further increased by photon RT which leads to enhanced expression of fibronectin receptor integrins. HPV16-associated E2 gene disruption is a main predictor of treatment-refractory cancer virulence. E2 gene disruption promotes cell motility. Following photon RT, E2-disrupted tumors bear the risk of integrin-related infiltration and dissemination. (orig.) [German] Persistierende Infektionen mit humanen Papillomaviren 16 (HPV16) sind ein Hauptausloeser des Zervixkarzinoms. Die Integration der viralen DNS in das Wirtszellgenom fuehrt zum Integritaetsverlust des E2-Gens, wodurch in der Wirtszelle Apoptose verhindert und Motilitaet gesteigert werden. In

  2. Spinocellular carcinoma from warts in a HPV infection natural history lasting 49 years. Virus strategy or host choice? Implications for researches and therapeutic vaccines.

    Science.gov (United States)

    Criscione, S M

    2011-11-01

    There is a very strong evidence that progression (also to cancer) in variable percentages of cases infected by HPV, HBV, HCV, and HIV depends on host immune response. A large number of observations demonstrate that virus set up a postulated "active strategy" to modify host reactions or to avoid it. But in all those infections it also seems that antigen load (viral RNA or DNA), chronic activation of immune response and time elapsing from the primary infection play a pivotal role in determining clearing or persisting outcomes. My wife's HPV and cancer natural history, lasting 49 years, started at the age of 10 years with facial warts and progressed to CIN 2/3, cervical in situ carcinoma, perineal warts, perianal carcinoma, inguinal lymph nodes, and invasion of bones and muscular structures, until death is paradigmatic: a progressive immune failure was detected in her scaling up all those clinical features, ending in a massive apoptosis of her lymphocytes collected by leukapheresis and cultured with HPV antigens E6/E7, with the aim of obtaining antigen presenting cells and CD8+ specific T lymphocytes. From this experience, a concept of "host choice to reach a tolerance (mainly by a Tregs mediated anergy) or symbiotic-like state" arises, underlining all the affected host's immune-responses to virus persistence (and to consequent tumors). It might be then postulated as the hallmark of a long-term host/parasites co-evolution, and considered a "normal" reaction when the host faces overwhelming numbers of non-self cancer cells (high antigen loads) preceded by persistent virus infections (chronic activation). This happens in patients who do not clear HPV or other viruses soon enough after infection. These observations may lead to a better understanding of many phenomena that are actually difficult to explain or still are open questions. The auto-limiting host's immune-responses are likely to be aimed to avoid risks arising mainly in the protection of "self" (autoimmunity

  3. Double positivity for HPV DNA/p16 in tonsillar and base of tongue cancer improves prognostication

    DEFF Research Database (Denmark)

    Garnaes, Emilie; Frederiksen, Kirsten; Kiss, Katalin

    2016-01-01

    of tongue squamous cell carcinoma (BSCC) when stratifying for HPV DNA status, p16 expression and combined HPV/p16 status. We included all patients (n = 797) diagnosed with TSCCs and BSCCs in Eastern Denmark as registered in the Danish Head and Neck Cancer Group (DAHANCA) database and the Danish Pathology...... Databank, 2000–2010. Patients were treated according to national guidelines (radiotherapy +/− concomitant cisplatin). All specimens were analysed using HPV DNA PCR and p16 immunohistochemistry. Clinical information was retrieved from the DAHANCA database and the Danish National Patient Registry....... Information on vital status was obtained from the Danish Civil Registration System. We observed improved OS for HPV+/p16+ BSCCs compared to HPV−/p16− (hazard ratio for death [HR], 0.15; 95% CI, 0.09–0.24). Among STSCCs, HPV+/p16+ showed the lowest HR (0.19, 95% CI, 0.13–0.29); whereas, HPV−/p16+ showed...

  4. Control of HPV infection and related cancer through vaccination.

    Science.gov (United States)

    Tran, Nam Phuong; Hung, Chien-Fu; Roden, Richard; Wu, T-C

    2014-01-01

    Human papillomavirus (HPV), the most common sexually transmitted virus, and its associated diseases continue to cause significant morbidity and mortality in over 600 million infected individuals. Major progress has been made with preventative vaccines, and clinical data have emerged regarding the efficacy and cross-reactivity of the two FDA approved L1 virus like particle (VLP)-based vaccines. However, the cost of the approved vaccines currently limits their widespread use in developing countries which carry the greatest burden of HPV-associated diseases. Furthermore, the licensed preventive HPV vaccines only contain two high-risk types of HPV (HPV-16 and HPV-18) which can protect only up to 75 % of all cervical cancers. Thus, second generation preventative vaccine candidates hope to address the issues of cost and broaden protection through the use of more multivalent L1-VLPs, vaccine formulations, or alternative antigens such as L1 capsomers, L2 capsid proteins, and chimeric VLPs. Preventative vaccines are crucial to controlling the transmission of HPV, but there are already hundreds of millions of infected individuals who have HPV-associated lesions that are silently progressing toward malignancy. This raises the need for therapeutic HPV vaccines that can trigger T cell killing of established HPV lesions, including HPV-transformed tumor cells. In order to stimulate such antitumor immune responses, therapeutic vaccine candidates deliver HPV antigens in vivo by employing various bacterial, viral, protein, peptide, dendritic cell, and DNA-based vectors. This book chapter will review the commercially available preventive vaccines, present second generation candidates, and discuss the progress of developing therapeutic HPV vaccines.

  5. Therapeutic Potential of Delivering Arsenic Trioxide into HPV-Infected Cervical Cancer Cells Using Liposomal Nanotechnology

    Science.gov (United States)

    Wang, Xiaoyan; Li, Dong; Ghali, Lucy; Xia, Ruidong; Munoz, Leonardo P.; Garelick, Hemda; Bell, Celia; Wen, Xuesong

    2016-02-01

    Arsenic trioxide (ATO) has been used successfully to treat acute promyelocytic leukaemia, and since this discovery, it has also been researched as a possible treatment for other haematological and solid cancers. Even though many positive results have been found in the laboratory, wider clinical use of ATO has been compromised by its toxicity at higher concentrations. The aim of this study was to explore an improved method for delivering ATO using liposomal nanotechnology to evaluate whether this could reduce drug toxicity and improve the efficacy of ATO in treating human papillomavirus (HPV)-associated cancers. HeLa, C33a, and human keratinocytes were exposed to 5 μm of ATO in both free and liposomal forms for 48 h. The stability of the prepared samples was tested using inductively coupled plasma optical emission spectrometer (ICP-OES) to measure the intracellular arsenic concentrations after treatment. Fluorescent double-immunocytochemical staining was carried out to evaluate the protein expression levels of HPV-E6 oncogene and caspase-3. Cell apoptosis was analysed by flow cytometry. Results showed that liposomal ATO was more effective than free ATO in reducing protein levels of HPV-E6 and inducing cell apoptosis in HeLa cells. Moreover, lower toxicity was observed when liposomal-delivered ATO was used. This could be explained by lower intracellular concentrations of arsenic. The slowly accumulated intracellular ATO through liposomal delivery might act as a reservoir which releases ATO gradually to maintain its anti-HPV effects. To conclude, liposome-delivered ATO could protect cells from the direct toxic effects induced by higher concentrations of intracellular ATO. Different pathways may be involved in this process, depending on local architecture of the tissues and HPV status.

  6. HPV-FASTER

    DEFF Research Database (Denmark)

    Bosch, F Xavier; Robles, Claudia; Díaz, Mireia

    2016-01-01

    Human papillomavirus (HPV)-related screening technologies and HPV vaccination offer enormous potential for cancer prevention, notably prevention of cervical cancer. The effectiveness of these approaches is, however, suboptimal owing to limited implementation of screening programmes and restricted...... indications for HPV vaccination. Trials of HPV vaccination in women aged up to 55 years have shown almost 90% protection from cervical precancer caused by HPV16/18 among HPV16/18-DNA-negative women. We propose extending routine vaccination programmes to women of up to 30 years of age (and to the 45-50-year...... age groups in some settings), paired with at least one HPV-screening test at age 30 years or older. Expanding the indications for HPV vaccination and much greater use of HPV testing in screening programmes has the potential to accelerate the decline in cervical cancer incidence. Such a combined...

  7. HPV DNA, E6/E7 mRNA, and p16INK4a detection in head and neck cancers: a systematic review and meta-analysis.

    Science.gov (United States)

    Ndiaye, Cathy; Mena, Marisa; Alemany, Laia; Arbyn, Marc; Castellsagué, Xavier; Laporte, Louise; Bosch, F Xavier; de Sanjosé, Silvia; Trottier, Helen

    2014-11-01

    We aimed to provide updated information about the global estimates of attributable fraction and type distribution of human papillomavirus (HPV) in head and neck squamous cell carcinomas by doing a systematic review and meta-analysis. We did a literature search on PubMed to identify studies that used PCR for detection of HPV DNA in head and neck squamous cell carcinomas with information about HPV genotype distribution. We included studies that tested 20 or more biopsies per cancer site and were published between July 15, 1990, and Feb 29, 2012. We collected information about sex, risk factors, HPV detection methods, and biomarkers of potentially HPV-induced carcinogenesis (E6/E7 mRNA and p16(INK4a)). If it was not possible to abstract the required information directly from the paper, we contacted the authors. We did a meta-analysis to produce pooled prevalence estimates including a meta-regression to explore sources of heterogeneity. 148 studies were included, contributing data for 12 163 cases of head and neck squamous cell carcinoma from 44 countries. HPV DNA was detected in 3837 cases. HPV16 accounted for 82·2% (95% CI 77·7-86·4) of all HPV DNA positive cases. By cancer site, pooled HPV DNA prevalence estimates were 45·8% (95% CI 38·9-52·9) for oropharynx, 22·1% (16·4-28·3) for larynx (including hypopharynx), and 24·2% (18·7-30·2) for oral cavity. The percent positivity of p16(INK4a) positive cases in HPV-positive oropharyngeal cancer cases was 86·7% (95% CI 79·2-92·9) and of E6/E7 mRNA positive cases was 86·9% (73·2-96·8). The estimate of HPV attributable fraction in oropharyngeal cancer defined by expression of positive cases of E6/E7 mRNA was 39·8% and of p16(INK4a) was 39·7%. Of subsites, tonsils (53·9%, 95% CI 46·4-61·3) had the highest HPV DNA prevalence. HPV DNA prevalence varied significantly by anatomical site, geographic region, but not by sex or tobacco or alcohol consumption. The contribution of HPV prevalence in head and neck

  8. Triage of HR-HPV Positive Women with Minor Cytological Abnormalities: A Comparison of mRNA Testing, HPV DNA Testing, and Repeat Cytology Using a 4-Year Follow-Up of a Population-Based Study

    Science.gov (United States)

    Persson, Maria; Elfström, K. Miriam; Brismar Wendel, Sophia; Weiderpass, Elisabete; Andersson, Sonia

    2014-01-01

    Objective Expression of the viral E6/E7 oncogenes of high-risk human papillomaviruses (HR-HPV) is necessary for malignant conversion and maintenance in cervical tissue. In order to determine whether HR-HPV E6/E7 mRNA testing more effectively predicts precancerous lesions and invasive cervical cancer than HR-HPV DNA testing, we aimed to compare triage using HR-HPV E6/E7 mRNA testing by APTIMA HPV Assay (APTIMA) to HPV16 DNA testing, HPV16/18 DNA testing, and repeat cytology. Methods Liquid-based (PreservCyt) cell samples were obtained from HR-HPV-positive women diagnosed with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) within the framework of the population-based cervical cancer screening program in Stockholm, Sweden. Samples were tested for HR-HPV E6/E7 mRNA by APTIMA (Gene-Probe Inc., San Diego, CA, USA). Women were followed up for 4 years after the index cytology via medical and laboratory records, and the Stockholm Oncology Center. Results Nine of 25 (36%) women in the ASCUS group, and 64 of 180 (36%) women in the LSIL group developed cervical intraepithelial neoplasia (CIN) grade 2 or worse during 4 years of follow-up. 162 (74%) women were APTIMA-positive, and APTIMA had the highest sensitivity to predict CIN2 or worse and CIN3 or worse in the ASCUS (77.8% and 100%) and LSIL (78.1 and 75.8%) groups, although specificity was insufficient (ASCUS. More focused investigation is required for women with LSIL. PMID:24587193

  9. Triage of HR-HPV positive women with minor cytological abnormalities: a comparison of mRNA testing, HPV DNA testing, and repeat cytology using a 4-year follow-up of a population-based study.

    Science.gov (United States)

    Persson, Maria; Elfström, K Miriam; Brismar Wendel, Sophia; Weiderpass, Elisabete; Andersson, Sonia

    2014-01-01

    Expression of the viral E6/E7 oncogenes of high-risk human papillomaviruses (HR-HPV) is necessary for malignant conversion and maintenance in cervical tissue. In order to determine whether HR-HPV E6/E7 mRNA testing more effectively predicts precancerous lesions and invasive cervical cancer than HR-HPV DNA testing, we aimed to compare triage using HR-HPV E6/E7 mRNA testing by APTIMA HPV Assay (APTIMA) to HPV16 DNA testing, HPV16/18 DNA testing, and repeat cytology. Liquid-based (PreservCyt) cell samples were obtained from HR-HPV-positive women diagnosed with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) within the framework of the population-based cervical cancer screening program in Stockholm, Sweden. Samples were tested for HR-HPV E6/E7 mRNA by APTIMA (Gene-Probe Inc., San Diego, CA, USA). Women were followed up for 4 years after the index cytology via medical and laboratory records, and the Stockholm Oncology Center. Nine of 25 (36%) women in the ASCUS group, and 64 of 180 (36%) women in the LSIL group developed cervical intraepithelial neoplasia (CIN) grade 2 or worse during 4 years of follow-up. 162 (74%) women were APTIMA-positive, and APTIMA had the highest sensitivity to predict CIN2 or worse and CIN3 or worse in the ASCUS (77.8% and 100%) and LSIL (78.1 and 75.8%) groups, although specificity was insufficient (cytology were more specific than APTIMA. The results of this population-based study with comprehensive follow-up support the use of APTIMA as a triage test for women with ASCUS. More focused investigation is required for women with LSIL.

  10. Introducing a High-Risk HPV DNA Test Into a Public Sector Screening Program in El Salvador.

    Science.gov (United States)

    Cremer, Miriam L; Maza, Mauricio; Alfaro, Karla M; Kim, Jane J; Ditzian, Lauren R; Villalta, Sofia; Alonzo, Todd A; Felix, Juan C; Castle, Philip E; Gage, Julia C

    2016-04-01

    In a primary human papillomavirus (HPV) screening program, we compared the 6-month follow-up among colposcopy and noncolposcopy-based management strategies for screen-positive women. Women aged 30 to 49 years were screened with HPV DNA tests using both self-collection and provider collection of samples. Women testing positive received either (1) colposcopy management (CM) consisting of colposcopy and management per local guidelines or (2) screen-and-treat (ST) management using visual inspection with acetic acid to determine cryotherapy eligibility, with eligible women undergoing immediate cryotherapy. One thousand women were recruited in each cohort. Of these, 368 (18.4%) of 2000 women were recruited using a more intensive outreach strategy. Demographics, HPV positivity, and treatment compliance were compared across recruitment and management strategies. More women in the ST cohort received treatment within 6 months compared with those in the CM cohort (117/119 [98.3%] vs 64/93 [68.8%]; p < .001). Women recruited through more intensive outreach were more likely to be HPV positive, lived in urban areas, were more educated, and had higher numbers of lifetime sexual partners and fewer children. Women in the CM arm were less likely to complete care than women in the ST arm. Targeted outreach to underscreened women successfully identified women with higher prevalence of HPV and possibly higher disease burden.

  11. HPV types in cervical cancer tissue in South Africa: A head-to-head comparison by mRNA and DNA tests.

    Science.gov (United States)

    Rad, Amir; Sørbye, Sveinung Wergeland; Dreyer, Greta; Hovland, Siri; Falang, Bente Marie; Louw, Melanie; Skjeldestad, Finn Egil

    2017-11-01

    Accurate identification of human papillomavirus (HPV)-types in cervical cancer tissue may be important for tailoring tests for primary screening and types to be included in a vaccine. The aim of this study was to compare test-performance of a 45-type HPV deoxyribonucleic acid (DNA)-test with a 9-type HPV messenger ribonucleic acid (mRNA)-test in cervical cancer tissues.In a case-series design 188 women with diagnosed cervical cancer during the period January 2008 to July 1, 2011 at the Gynaecological Oncology Unit, University of Pretoria, South Africa were recruited to the study. After cases with negative internal controls for DNA/mRNA detection (n = 18) and unconfirmed histology (n = 3) of cervical cancer were excluded, 167 women remained eligible for analysis. We compared 45 DNA-types detected through general primer (GP)5/6 polymerase chain reaction (PCR) and reverse line blot (RLB) genotyping with a modified version of the mRNA test PreTect HPV-Proofer detecting 9 genotypes (16, 18, 31, 33, 35, 45, 51, 52, 58).Histological types were 92.2% squamous cell carcinoma, 4.8% adenocarcinoma, and 3.0% adenosquamous carcinoma. Overall, HPV was detected in 95.2% (159/167) of specimens. The DNA- and mRNA tests each rendered 153/167 (91.6%) HPV positive results. When restricting the analysis to the 9 high-risk HPV-types included in the mRNA test, 91.6% (153/167) and 88.0% (147/167) were positive by the mRNA- and DNA-tests (P = .28), respectively. After hierarchical categorization of 9 comparable types, we found concordance in 66 of 67 specimens for HPV16, 25 of 27 specimens for HPV18, 19 of 21 specimens for HPV45, and only in 33 of 45 for HPV31, 33, 35, 51, 52, 58. The positivity rate for the HPV types 16, 18, and 45 and the positivity rate for HPV 16, 18, 45, 33 and 35 by both tests was 66% to 68% and 80% to 83%, respectively.Overall and when considering established high-risk types, the mRNA test has at least as high detection rate as the DNA test. The m

  12. Gene therapeutics and DNA vaccines; quality and regulatory aspects

    NARCIS (Netherlands)

    Schalk JAC; Hegger I; Jongen PMJM; LGM

    2001-01-01

    Transfer of genes to cells and the subsequent expression of these genes can alleviate the symptoms of a disease (gene therapy), or prevent infectious diseases (DNA vaccination). Gene therapy and DNA vaccination are based on relatively new technologies. The first gene therapeutics are expected to

  13. DNA molecules and human therapeutics | Danquah | African Journal ...

    African Journals Online (AJOL)

    Nucleic acid molecules are championing a new generation of reverse engineered biopharmaceuticals. In terms of potential application in gene medicine, plasmid DNA (pDNA) vectors have exceptional therapeutic and immunological profiles as they are free from safety concerns associated with viral vectors, display ...

  14. HPV 5 and 8 E6 abrogate ATR activity resulting in increased persistence of UVB induced DNA damage.

    Directory of Open Access Journals (Sweden)

    Nicholas A Wallace

    Full Text Available The role of the E6 oncoprotein from high-risk members of the α human papillomavirus genus in anogenital cancer has been well established. However, far less is known about the E6 protein from the β human papillomavirus genus (β-HPVs. Some β-HPVs potentially play a role in non-melanoma skin cancer development, although they are not required for tumor maintenance. Instead, they may act as a co-factor that enhances the carcinogenic potential of UV damage. Indeed, the E6 protein from certain β-HPVs (HPV 5 and 8 promotes the degradation of p300, a histone acetyl transferase involved in UV damage repair. Here, we show that the expression of HPV 5 and 8 E6 increases thymine dimer persistence as well as the likelihood of a UVB induced double strand break (DSB. Importantly, we provide a mechanism for the increased DNA damage by showing that both extended thymine dimer persistence as well as elevated DSB levels are dependent on the ability of HPV 8 E6 to promote p300 degradation. We further demonstrate that HPV 5 and 8 E6 expression reduces the mRNA and protein levels of ATR, a PI3 kinase family member that plays a key role in UV damage signaling, but that these levels remain unperturbed in cells expressing a mutated HPV 8 E6 incapable of promoting p300 degradation. We confirm that the degradation of p300 leads to a reduction in ATR protein levels, by showing that ATR levels rebound when a p300 mutant resistant to HPV 8 mediated degradation and HPV 8 E6 are co-transfected. Conversely, we show that ATR protein levels are reduced when p300 is targeted for degradation by siRNA. Moreover, we show the reduced ATR levels in HPV 5 and 8 E6 expressing cells results in delayed ATR activation and an attenuated ability of cells to phosphorylate, and as a result accumulate, p53 in response to UVB exposure, leading to significantly reduced cell cycle arrest. In conclusion, these data demonstrate that β-HPV E6 expression can enhance the carcinogenic potential of

  15. Photon-induced cell migration and integrin expression promoted by DNA integration of HPV16 genome.

    Science.gov (United States)

    Rieken, Stefan; Simon, Florian; Habermehl, Daniel; Dittmar, Jan Oliver; Combs, Stephanie E; Weber, Klaus; Debus, Jürgen; Lindel, Katja

    2014-10-01

    Persistent human papilloma virus 16 (HPV16) infections are a major cause of cervical cancer. The integration of the viral DNA into the host genome causes E2 gene disruption which prevents apoptosis and increases host cell motility. In cervical cancer patients, survival is limited by local infiltration and systemic dissemination. Surgical control rates are poor in cases of parametrial infiltration. In these patients, radiotherapy (RT) is administered to enhance local control. However, photon irradiation itself has been reported to increase cell motility. In cases of E2-disrupted cervical cancers, this phenomon would impose an additional risk of enhanced tumor cell motility. Here, we analyze mechanisms underlying photon-increased migration in keratinocytes with differential E2 gene status. Isogenic W12 (intact E2 gene status) and S12 (disrupted E2 gene status) keratinocytes were analyzed in fibronectin-based and serum-stimulated migration experiments following single photon doses of 0, 2, and 10 Gy. Quantitative FACS analyses of integrin expression were performed. Migration and adhesion are increased in E2 gene-disrupted keratinocytes. E2 gene disruption promotes attractability by serum components, therefore, effectuating the risk of local infiltration and systemic dissemination. In S12 cells, migration is further increased by photon RT which leads to enhanced expression of fibronectin receptor integrins. HPV16-associated E2 gene disruption is a main predictor of treatment-refractory cancer virulence. E2 gene disruption promotes cell motility. Following photon RT, E2-disrupted tumors bear the risk of integrin-related infiltration and dissemination.

  16. Is HPV DNA testing specificity comparable to that of cytological testing in primary cervical cancer screening? Results of a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Pileggi, Claudia; Flotta, Domenico; Bianco, Aida; Nobile, Carmelo G A; Pavia, Maria

    2014-07-01

    Human-papillomavirus (HPV) DNA testing has been proposed as an alternative to primary cervical cancer screening using cytological testing. Review of the evidence shows that available data are conflicting for some aspects. The overall goal of the study is to update the performance of HPV DNA as stand-alone testing in primary cervical cancer screening, focusing particularly on the aspects related to the specificity profile of the HPV DNA testing in respect to cytology. We performed a meta-analysis of randomized controlled clinical trials. Eight articles were included in the meta-analysis. Three outcomes have been investigated: relative detection, relative specificity, and relative positive predictive value (PPV) of HPV DNA testing versus cytology. Overall evaluation of relative detection showed a significantly higher detection of CIN2+ and CIN3+ for HPV DNA testing versus cytology. Meta-analyses that considered all age groups showed a relative specificity that favored the cytology in detecting both CIN2+ and CIN3+ lesions whereas, in the ≥30 years' group, specificity of HPV DNA and cytology tests was similar in detecting both CIN2+ and CIN3+ lesions. Results of the pooled analysis on relative PPV showed a not significantly lower PPV of HPV DNA test over cytology. A main key finding of the study is that in women aged ≥30, has been found an almost overlapping specificity between the two screening tests in detecting CIN2 and above-grade lesions. Therefore, primary screening of cervical cancer by HPV DNA testing appears to offer the right balance between maximum detection of CIN2+ and adequate specificity, if performed in the age group ≥30 years. © 2013 UICC.

  17. Post Hoc Analysis of the PATRICIA Randomized Trial of the Efficacy of Human Papillomavirus Type 16 (HPV-16)/HPV-18 AS04-Adjuvanted Vaccine against Incident and Persistent Infection with Nonvaccine Oncogenic HPV Types Using an Alternative Multiplex Type-Specific PCR Assay for HPV DNA

    Science.gov (United States)

    Colau, Brigitte; Wheeler, Cosette M.; Naud, Paulo; Garland, Suzanne; Quint, Wim; Chow, Song-Nan; Salmerón, Jorge; Lehtinen, Matti; Del Rosario-Raymundo, M. Rowena; Paavonen, Jorma; Teixeira, Júlio C.; Germar, Maria Julieta; Peters, Klaus; Skinner, S. Rachel; Limson, Genara; Castellsagué, Xavier; Poppe, Willy A. J.; Ramjattan, Brian; Klein, Terry D.; Schwarz, Tino F.; Chatterjee, Archana; Tjalma, Wiebren A. A.; Diaz-Mitoma, Francisco; Lewis, David J. M.; Harper, Diane M.; Molijn, Anco; van Doorn, Leen-Jan; David, Marie-Pierre; Dubin, Gary

    2014-01-01

    The efficacy of the human papillomavirus type 16 (HPV-16)/HPV-18 AS04-adjuvanted vaccine against cervical infections with HPV in the Papilloma Trial against Cancer in Young Adults (PATRICIA) was evaluated using a combination of the broad-spectrum L1-based SPF10 PCR-DNA enzyme immunoassay (DEIA)/line probe assay (LiPA25) system with type-specific PCRs for HPV-16 and -18. Broad-spectrum PCR assays may underestimate the presence of HPV genotypes present at relatively low concentrations in multiple infections, due to competition between genotypes. Therefore, samples were retrospectively reanalyzed using a testing algorithm incorporating the SPF10 PCR-DEIA/LiPA25 plus a novel E6-based multiplex type-specific PCR and reverse hybridization assay (MPTS12 RHA), which permits detection of a panel of nine oncogenic HPV genotypes (types 16, 18, 31, 33, 35, 45, 52, 58, and 59). For the vaccine against HPV types 16 and 18, there was no major impact on estimates of vaccine efficacy (VE) for incident or 6-month or 12-month persistent infections when the MPTS12 RHA was included in the testing algorithm versus estimates with the protocol-specified algorithm. However, the alternative testing algorithm showed greater sensitivity than the protocol-specified algorithm for detection of some nonvaccine oncogenic HPV types. More cases were gained in the control group than in the vaccine group, leading to higher point estimates of VE for 6-month and 12-month persistent infections for the nonvaccine oncogenic types included in the MPTS12 RHA assay (types 31, 33, 35, 45, 52, 58, and 59). This post hoc analysis indicates that the per-protocol testing algorithm used in PATRICIA underestimated the VE against some nonvaccine oncogenic HPV types and that the choice of the HPV DNA testing methodology is important for the evaluation of VE in clinical trials. (This study has been registered at ClinicalTrials.gov under registration no. NCT00122681.) PMID:25540273

  18. Threshold cost-effectiveness analysis for a therapeutic vaccine against HPV-16/18-positive cervical intraepithelial neoplasia in the Netherlands

    NARCIS (Netherlands)

    Luttjeboer, Jos; Setiawan, Didik; Cao, Qi; Daemen, Toos CAHH; Postma, Maarten J.

    2016-01-01

    In this study, the potential price for a therapeutic vaccine against Human Papilloma Virus (HPV)-16 & 18 (pre)-malignant cervical lesions is examined. A decision tree model was built in the context of the new Dutch cervical cancer-screening program and includes a primary test for the presence of

  19. Concordance of HPV-DNA in cervical dysplasia or genital warts in women and their monogamous long-term male partners.

    Science.gov (United States)

    Rob, Filip; Tachezy, Ruth; Pichlík, Tomáš; Škapa, Petr; Rob, Lukáš; Hamšíková, Eva; Šmahelová, Jana; Hercogová, Jana

    2017-09-01

    Transmission of human papillomavirus (HPV) is a premise for development of cervical dysplasia and genital warts (GWs). This cross-sectional study assesses concordance of HPV types present in GWs or cervical dysplasia in women and genital infection of their monogamous male partners in conjunction with seroprevalence of HPV-6, -11, -16, and -18 antibodies. Blood was taken from both women and men, as well a smear of the urogenital area of men. HPV DNA detection in women was done in fixed paraffin embedded tissues under histological control. Of 143 couples who agreed to participate in the study, 68 met inclusion criteria. Type-specific concordance was observed in 32.5% (13/40) of couples in which women had genital warts and in 32.1% (9/28) of couples in which women had cervical dysplasia. In multivariate analysis only smoking in women was associated with concordance (P HPV-specific antibodies was high in male partners, but was not associated with presence of the same HPV type on their genitals. The same type-specific HPV antibodies were detected in 81.8% of men in couples with HPV-6 concordant genital warts, but only in 14.3% of men in couples with HPV-16 concordant cervical dysplasia (P HPV concordance in genital warts and cervical dysplasia lesions of women and genital infection of their male partners is common and similar. Higher seroconversion in couples with HPV-6 concordant genital warts compared with couples with HPV-16 concordant cervical dysplasia may be explained by viral load exposure. © 2017 Wiley Periodicals, Inc.

  20. Aptamer-targeted DNA nanostructures for therapeutic delivery.

    Science.gov (United States)

    Charoenphol, Phapanin; Bermudez, Harry

    2014-05-05

    DNA-based nanostructures have been widely used in various applications due to their structural diversity, programmability, and uniform structures. Their intrinsic biocompatibility and biodegradability further motivates the investigation of DNA-based nanostructures as delivery vehicles. Incorporating AS1411 aptamers into DNA pyramids leads to enhanced intracellular uptake and selectively inhibits the growth of cancer cells, achieved without the use of transfection reagents. Furthermore, aptamer-displaying pyramids are found to be substantially more resistant to nuclease degradation than single-stranded aptamers. These findings, along with their modularity, reinforce the potential of DNA-based nanostructures for therapeutic applications.

  1. A DNA vaccine encoding mutated HPV58 mE6E7-Fc-GPI fusion antigen and GM-CSF and B7.1

    Directory of Open Access Journals (Sweden)

    Wang H

    2015-10-01

    Full Text Available He Wang,1 Jiyun Yu,2 Li Li1 1Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, 2Institute of Basic Medical Sciences, Academy of Military Medical Sciences, Beijing, People’s Republic of China Background: Persistent infection with high-risk human papillomavirus (HPV is a predominant cause of cervical cancer, and HPV58 is the third most common virus detected in the patients with cervical cancer in Asia. E6 and E7 are the viral oncogenes which are constitutively expressed in HPV-associated tumor cells and can be used as target antigens for related immunotherapy. In this study, we modified the HPV58 E6 and E7 oncogenes to eliminate their oncogenic potential and constructed a recombinant DNA vaccine that coexpresses the sig-HPV58 mE6E7-Fc-GPI fusion antigen in addition to granulocyte-macrophage colony-stimulating factor (GM-CSF and B7.1 as molecular adjuvants (PVAX1-HPV58 mE6E7FcGB for the treatment of HPV58 (+ cancer. Methods: PVAX1-HPV58 mE6E7FcGB recombinant DNA vaccine was constructed to express a fusion protein containing a signal peptide, a modified HPV58 mE6E7 gene, and human IgG Fc and glycosylphosphatidylinositol (GPI-anchoring sequences using the modified DNA vaccine vector PVAX1-IRES-GM/B7.1 that coexpresses GM-CSF, and B7.1. C57BL/6 mice were challenged by HPV58 E6E7-expressing B16-HPV58 E6E7 cells, followed by immunization by PVAX1-HPV58 mE6E7FcGB vaccine on days 7, 14, 21 after tumor challenge. The cellular immune responses in immunized mice were assessed by measuring IFN-γ production in splenocytes upon stimulation by HPV58 E6E7-GST protein and the lysis of B16-HPV58 E6E7 target cells by splenocytes after restimulation with HPV58 E6E7-GST protein. The antitumor efficacy was evaluated by monitoring the growth of the tumor. Results: PVAX1-HPV58 mE6E7FcGB elicited varying levels of IFN-lsgdB58onn T-cell immune responses and lysis of target cell in mice in response to the

  2. High-Risk Human Papillomavirus (hrHPV) E6/E7 mRNA Testing by PreTect HPV-Proofer for Detection of Cervical High-Grade Intraepithelial Neoplasia and Cancer among hrHPV DNA-Positive Women with Normal Cytology

    Science.gov (United States)

    Rijkaart, D. C.; Heideman, D. A. M.; Coupe, V. M. H.; Brink, A. A. T. P.; Verheijen, R. H. M.; Skomedal, H.; Karlsen, F.; Morland, E.; Snijders, P. J. F.

    2012-01-01

    Our aim was to investigate whether high-risk HPV (hrHPV) mRNA detection by PreTect HPV-Proofer can be used to stratify hrHPV DNA-positive women of different cytology classes for risk of high-grade cervical intraepithelial neoplasia or worse (cervical precancer or cancer, i.e., cervical intraepithelial neoplasia grade 2 or higher [≥CIN2]). A total of 375 women participating in population-based screening, with a GP5+/6+-PCR hrHPV DNA-positive cervical scrape with normal cytology (n = 202), borderline or mild dyskaryosis (BMD) (n = 88), or moderate dyskaryosis or worse (>BMD) (n = 85), were enrolled. Cervical scrapes were additionally subjected to HPV16/18/31/33/45 E6/E7 mRNA analysis by PreTect HPV-Proofer (mRNA test). Referral and follow-up policies were based on cytology, hrHPV DNA, and mRNA testing. The primary study endpoint was the number of ≥CIN2 detected within 3 years of follow-up. The mRNA positivity increased with the severity of cytological abnormality, ranging from 32% (64/202) in hrHPV DNA-positive women with normal cytology to 47% (41/88) in BMD and 68% (58/85) in >BMD groups (P cytology, i.e., 0.55 (95% confidence interval [95% CI], 0.34 to 0.76) in mRNA-positive versus 0.20 (95% CI, 0.07 to 0.33) in mRNA-negative women. In hrHPV DNA-positive women with BMD or >BMD, the result of the mRNA test did not influence the ≥CIN2 risk. In conclusion, mRNA testing by PreTect HPV-Proofer might be of value to select hrHPV DNA-positive women with normal cytology in need of immediate referral for colposcopy. PMID:22553244

  3. Human Papillomavirus DNA methylation as a biomarker for cervical precancer: Consistency across 12 genotypes and potential impact on management of HPV-positive women.

    Science.gov (United States)

    Clarke, Megan A; Gradíssimo, Ana; Schiffman, Mark; Lam, Jessica; Sollecito, Christopher C; Fetterman, Barbara; Lorey, Thomas; Poitras, Nancy E; Raine-Bennett, Tina; Castle, Philip E; Wentzensen, Nicolas; Burk, Robert D

    2018-02-02

    Human papillomavirus (HPV) DNA methylation testing is a promising triage option for women testing HPV-positive during cervical cancer screening. However, the extent to which methylation indicates precancer for all 12 carcinogenic HPV types has not been evaluated. In this nested case-control study, we tested up to 30 cases of precancer (CIN3/AIS) and 30 normal controls for each carcinogenic type (single infections with 16/18/31/33/35/39/45/51/52/56/58/59). Next-generation bisulfite sequencing was performed on CpG sites within the L1 and L2 genes. We calculated differences in methylation, odds ratios, and areas under the curve (AUC). Using a fixed sensitivity of 80%, we evaluated the specificity and the risk of CIN3/AIS for best performing CpG sites, and compared the performance of an explorative multi-type methylation assay with current triage strategies. Methylation was positively associated with CIN3/AIS across all 12 types. AUCs for the top sites ranged from 0.71 (HPV51 and HPV56) to 0.86 (HPV18). A combined 12-type methylation assay had the highest Youden's index (0.46), compared with cytology (0.31) and a 5-type methylation assay including only previously described types (0.26).  The 12-type methylation assay had higher sensitivity (80% vs. 76.6%) and lower test positivity compared to cytology (38.5% vs. 48.7%). The risk of CIN3/AIS was highest for methylation positives and lowest for cytology- or HPV16/18-positives. HPV DNA methylation is a general phenomenon marking the transition from HPV infection to precancer for all 12 carcinogenic types. Development of a combined multi-type methylation assay may serve as a triage test for HPV-positive women. Copyright ©2018, American Association for Cancer Research.

  4. Comparison of the performance of the NucliSENS EasyQ HPV E6/E7 mRNA assay and HPV DNA chip for testing squamous cell lesions of the uterine cervix.

    Science.gov (United States)

    Munkhdelger, Jijgee; Choi, Yeonim; Lee, Dongsup; Kim, Sunghyun; Kim, Geehyuk; Park, Sangjung; Choi, Eunhee; Jin, Hyunwoo; Jeon, Bo-Young; Lee, Hyeyoung; Park, Kwang Hwa

    2014-08-01

    This study aims to evaluate the clinical performance of the NucliSENS EasyQ assay and compare it with HPV DNA genotyping for the detection of high-grade squamous intraepithelial lesions (HSIL) and cancer in a Korean population. In 188 total thin prep samples, the remaining fluid after cytology slide preparation was tested with Goodgene HPV DNA chips and the NucliSENS EasyQ HPV E6/E7 messenger RNA (mRNA) assay. The sensitivity and specificity of each test were calculated with HSIL and squamous cell carcinoma (SCC) as the disease endpoint. Out of the 188 samples, 139 (74%) were positive for DNA of 14 HPV types, while 57 (30%) cases were positive for E6/E7 mRNA. The DNA test was positive in cytology cases of SCC, HSIL, and atypical squamous cell. The mRNA test yielded results of 75%, 74%, 60%, 56%, and 29% positivity in abnormal cytology cases of SCC, HSIL, atypical squamous cells - cannot exclude HSIL, atypical squamous cells of undetermined significance, and low-grade squamous intraepithelial lesion, respectively. In normal cytology cases, the positivity rates were 9% and 53% for the mRNA and DNA tests, respectively. For detection of HSIL and SCC, the sensitivity of the mRNA test was 74.36% and that of the DNA test was 100%, while the specificities of the tests were 85% and 40.83%, respectively. These findings suggest that the HPV E6/E7 mRNA assay can overcome the shortcoming of low specificity of DNA assays for clinical detection of high-grade cervical lesions and malignancies. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Sensitivity of APTIMA HPV E6/E7 mRNA test in comparison with hybrid capture 2 HPV DNA test for detection of high risk oncogenic human papillomavirus in 396 biopsy confirmed cervical cancers.

    Science.gov (United States)

    Basu, Partha; Banerjee, Dipanwita; Mittal, Srabani; Dutta, Sankhadeep; Ghosh, Ishita; Chowdhury, Nilarun; Abraham, Priya; Chandna, Puneet; Ratnam, Sam

    2016-07-01

    The sensitivity of E6/E7 mRNA-based Aptima HPV test (AHPV; Hologic, Inc.) for detection of cervical cancer has been reported based on only a small number of cases. We determined the sensitivity of AHPV in comparison with the DNA-based Hybrid Capture 2 HPV test (HC2; Qiagen) for the detection of oncogenic HPV in a large number of cervical cancers at the time of diagnosis using cervical samples obtained in ThinPrep (Hologic). Samples yielding discordant results were genotyped using Linear Array assay (LA; Roche). Of 396 cases tested, AHPV detected 377 (sensitivity, 95.2%; 95%CI: 93.1-97.3), and HC2 376 (sensitivity, 94.9%; 95%CI: 92.7-97.1) with an agreement of 97.2% (kappa 0.7; 95%CI: 0.54-0.87). Among six AHPV+/HC2- cases, LA identified oncogenic HPV types in four including a type 73 and was negative in two. Among five AHPV-/HC2+ cases, LA detected oncogenic HPV types in two including a type 73 and was negative in three. Of 14 AHPV-/HC2- cases, 13 were genotyped. LA detected oncogenic HPV types in six, non-oncogenic types in three, and was negative in four. This is the largest study to demonstrate the sensitivity of AHPV for the detection of invasive cervical cancer and this assay showed equal sensitivity to HC2. © 2015 Wiley Periodicals, Inc.

  6. Disruption of HPV16-E7 by CRISPR/Cas System Induces Apoptosis and Growth Inhibition in HPV16 Positive Human Cervical Cancer Cells

    Directory of Open Access Journals (Sweden)

    Zheng Hu

    2014-01-01

    Full Text Available High-risk human papillomavirus (HR-HPV has been recognized as a major causative agent for cervical cancer. Upon HPV infection, early genes E6 and E7 play important roles in maintaining malignant phenotype of cervical cancer cells. By using clustered regularly interspaced short palindromic repeats- (CRISPR- associated protein system (CRISPR/Cas system, a widely used genome editing tool in many organisms, to target HPV16-E7 DNA in HPV positive cell lines, we showed for the first time that the HPV16-E7 single-guide RNA (sgRNA guided CRISPR/Cas system could disrupt HPV16-E7 DNA at specific sites, inducing apoptosis and growth inhibition in HPV positive SiHa and Caski cells, but not in HPV negative C33A and HEK293 cells. Moreover, disruption of E7 DNA directly leads to downregulation of E7 protein and upregulation of tumor suppressor protein pRb. Therefore, our results suggest that HPV16-E7 gRNA guided CRISPR/Cas system might be used as a therapeutic strategy for the treatment of cervical cancer.

  7. Presence of High-Risk HPV mRNA in Relation to Future High-Grade Lesions among High-Risk HPV DNA Positive Women with Minor Cytological Abnormalities.

    Directory of Open Access Journals (Sweden)

    Hanna Johansson

    Full Text Available Continuous expression of E6- and E7-oncogenes of high-risk human papillomavirus (HPV types is necessary for the development and maintenance of the dysplastic phenotype. The aim of the study was to determine the sensitivity and specificity of the APTIMA HPV mRNA assay (Hologic in predicting future development of high-grade cervical intraepithelial neoplasia (CIN among high-risk HPV-DNA-positive women with atypical squamous cells of undetermined significance (ASCUS or low-grade squamous epithelial lesion (LSIL cytology.Archived SurePath cervical samples of women ≥ 35 years of age with high-risk HPV DNA-positive ASCUS (n = 211 or LSIL, (n = 131 were tested for the presence of high-risk HPV E6/E7 mRNA using the APTIMA HPV assay, and the women were monitored for development of histopathologically verified CIN2+.Twenty-nine percent (61/211 of the women in the ASCUS group, and 34.3% (45/131 in the LSIL group developed CIN2+ within 4.5 years of follow-up. The prevalence of HPV mRNA was 90.0% (95% CI 85.9-94.0 among women with ASCUS and 95.4% (95% CI 91.8-99.0 among women with LSIL. The presence of HPV E6/E7 mRNA was associated with future development of CIN2+ among women with ASCUS and LSIL (p=0.02. The mRNA assay demonstrated high sensitivity in predicting future CIN2+ and CIN3 for index ASCUS (96.7%; 95% CI 87.6-99.4 and 100%; 95% CI 82.2-100, respectively and LSIL (97.8%, 95% CI 86.8-99.9 and 100%, 95% CI 79.9-100, respectively. The corresponding specificity was low, 12.7% (95% CI 7.9-19.3 and 5.8% (95% CI 2.2-13.6, for future CIN2+, respectively. The negative predictive value of the HPV mRNA assay for detecting future CIN3 was 100%, since no mRNA-negative woman developed CIN3 (0/27 as compared to 13.6% (43/315 of the mRNA-positive women (p = 0.03.The APTIMA mRNA assay demonstrated high sensitivity but low specificity in predicting future CIN2+ among women with minor cytological abnormalities. The assay had high negative predictive value for future

  8. Presence of High-Risk HPV mRNA in Relation to Future High-Grade Lesions among High-Risk HPV DNA Positive Women with Minor Cytological Abnormalities

    Science.gov (United States)

    Johansson, Hanna; Bjelkenkrantz, Kaj; Darlin, Lotten; Dilllner, Joakim; Forslund, Ola

    2015-01-01

    Objective Continuous expression of E6- and E7-oncogenes of high-risk human papillomavirus (HPV) types is necessary for the development and maintenance of the dysplastic phenotype. The aim of the study was to determine the sensitivity and specificity of the APTIMA HPV mRNA assay (Hologic) in predicting future development of high-grade cervical intraepithelial neoplasia (CIN) among high-risk HPV-DNA-positive women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous epithelial lesion (LSIL) cytology. Methods Archived SurePath cervical samples of women ≥ 35 years of age with high-risk HPV DNA-positive ASCUS (n = 211) or LSIL, (n = 131) were tested for the presence of high-risk HPV E6/E7 mRNA using the APTIMA HPV assay, and the women were monitored for development of histopathologically verified CIN2+. Results Twenty-nine percent (61/211) of the women in the ASCUS group, and 34.3% (45/131) in the LSIL group developed CIN2+ within 4.5 years of follow-up. The prevalence of HPV mRNA was 90.0% (95% CI 85.9-94.0) among women with ASCUS and 95.4% (95% CI 91.8-99.0) among women with LSIL. The presence of HPV E6/E7 mRNA was associated with future development of CIN2+ among women with ASCUS and LSIL (p=0.02). The mRNA assay demonstrated high sensitivity in predicting future CIN2+ and CIN3 for index ASCUS (96.7%; 95% CI 87.6-99.4 and 100%; 95% CI 82.2-100, respectively) and LSIL (97.8%, 95% CI 86.8-99.9 and 100%, 95% CI 79.9-100, respectively). The corresponding specificity was low, 12.7% (95% CI 7.9-19.3) and 5.8% (95% CI 2.2-13.6), for future CIN2+, respectively. The negative predictive value of the HPV mRNA assay for detecting future CIN3 was 100%, since no mRNA-negative woman developed CIN3 (0/27) as compared to 13.6% (43/315) of the mRNA-positive women (p = 0.03). Conclusion The APTIMA mRNA assay demonstrated high sensitivity but low specificity in predicting future CIN2+ among women with minor cytological abnormalities. The assay had

  9. Status of carcinoma cervix and high risk HPV 16 DNA in women with postmenopausal uterine bleeding (PMB

    Directory of Open Access Journals (Sweden)

    Veena Kashyap

    2014-09-01

    Full Text Available Postmenopausal bleeding (PMB is a discharge that occurs following the firm diagnosis of menopause, which is at least six months from the end of women’s menstrual cycle but not to be confused with infrequent or irregular periods occurring around the time of menopause. It is a common problem representing 5% of all gynecology outpatient attendances which are to eliminate endometrial cancer as the cause of bleed and PMB should be reported urgently to the gynecologist. Uterine bleeding in postmenopausal women is highly indicative clinically of malignancy originating from cervix or endometrium and Human papilloma virus (HPV is one of the causative agent for carcinoma cervix. Incidence of carcinoma cervix increases with the age in mature women, however, incidence of human papillomavirus (HPV infection reduces as menopause sets in. The presence of the virus could be used as an early indication of disease potential. Because the Pap test can only detect clinical evidence of cervical disease, molecular-based diagnostic tools are being used more frequently to detect the virus before abnormal cell growth can be observed. This study was aimed to determine the status of cervical cancer and HPV 16 DNA positivity in relation to postmenopausal bleeding.

  10. Patterns of persistent HPV infection after treatment for cervical intraepithelial neoplasia (CIN): A systematic review.

    Science.gov (United States)

    Hoffman, Sarah R; Le, Tam; Lockhart, Alexandre; Sanusi, Ayodeji; Dal Santo, Leila; Davis, Meagan; McKinney, Dana A; Brown, Meagan; Poole, Charles; Willame, Corinne; Smith, Jennifer S

    2017-07-01

    A systematic review of the literature was conducted to determine the estimates of and definitions for human papillomavirus (HPV) persistence in women following treatment of cervical intra-epithelial neoplasia (CIN). A total of 45 studies presented data on post-treatment HPV persistence among 6,106 women. Most studies assessed HPV persistence after loop excision (42%), followed by conization (7%), cryotherapy (11%), laser treatment (4%), interferon-alpha, therapeutic vaccination, and photodynamic therapy (2% each) and mixed treatment (38%). Baseline HPV testing was conducted before or at treatment for most studies (96%). Follow-up HPV testing ranged from 1.5 to 80 months after baseline. Median HPV persistence tended to decrease with increasing follow-up time, declining from 27% at 3 months after treatment to 21% at 6 months, 15% at 12 months, and 10% at 24 months. Post-treatment HPV persistence estimates varied widely and were influenced by patient age, HPV-type, detection method, treatment method, and minimum HPV post-treatment testing interval. Loop excision and conization appeared to outperform cryotherapy procedures in terms of their ability to clear HPV infection. This systematic review provides evidence for the substantial heterogeneity in post-treatment HPV DNA testing practices and persistence estimates. © 2017 UICC.

  11. Molecular Pap smear: HPV genotype and DNA methylation of ADCY8, CDH8, and ZNF582 as an integrated biomarker for high-grade cervical cytology.

    Science.gov (United States)

    Shen-Gunther, Jane; Wang, Chiou-Miin; Poage, Graham M; Lin, Chun-Lin; Perez, Luis; Banks, Nancy A; Huang, Tim Hui-Ming

    2016-01-01

    The Pap smear has remained the foundation for cervical cancer screening for over 70 years. With advancements in molecular diagnostics, primary high-risk human papillomavirus (hrHPV) screening has recently become an accepted stand-alone or co-test with conventional cytology. However, both diagnostic tests have distinct limitations. The aim of this study was to determine the association between HPV genotypes and cellular epigenetic modifications in three grades of cervical cytology for screening biomarker discovery. This prospective, cross-sectional study used residual liquid-based cytology samples for HPV genotyping and epigenetic analysis. Extracted DNA was subjected to parallel polymerase chain reactions using three primer sets (MY09/11, FAP59/64, E6-E7 F/B) for HPV DNA amplification. HPV+ samples were genotyped by DNA sequencing. Promoter methylation of four candidate tumor suppressor genes (adenylate cyclase 8 (ADCY8), cadherin 8, type 2 (CDH8), MGMT, and zinc finger protein 582 (ZNF582)) out of 48 genes screened was quantified by bisulfite-pyrosequencing of genomic DNA. Independent validation of methylation profiles was performed by analyzing data from cervical cancer cell lines and clinical samples from The Cancer Genome Atlas (TCGA). Two hundred seventy-seven quality cytology samples were analyzed. HPV was detected in 31/100 (31 %) negative for intraepithelial lesion or malignancy (NILM), 95/100 (95 %) low-grade squamous intraepithelial lesion (LSIL), and 71/77 (92 %) high-grade squamous intraepithelial lesion (HSIL) samples. The proportion of IARC-defined carcinogenic HPV types in sequenced samples correlated with worsening grade: NILM 7/29 (24 %), LSIL 53/92 (58 %), and HSIL 65/70 (93 %). Promoter methylation of ADCY8, CDH8, and ZNF582 was measured in 170 samples: NILM (N = 33), LSIL (N = 70), and HSIL (N = 67) also correlated with worsening grade. Similar hypermethylation patterns were found in cancer cell lines and TCGA samples. The

  12. Oncogenic human papillomavirus imposes an instructive pattern of DNA methylation changes which parallel the natural history of cervical HPV infection in young women.

    Science.gov (United States)

    Leonard, Sarah M; Wei, Wenbin; Collins, Stuart I; Pereira, Merlin; Diyaf, Afaf; Constandinou-Williams, Christothea; Young, Lawrence S; Roberts, Sally; Woodman, Ciarán B

    2012-07-01

    The contribution of early virus-induced epigenetic changes to human papillomavirus (HPV)-associated carcinogenesis is poorly understood. Using genome-wide methylation array profiling and a cell-based model, which supports replication of HPV episomes, we found that transfection of primary human foreskin keratinocytes with episomal forms of high-risk HPV types was followed by upregulation of the DNA methyltransferases, DNMT1 and DNMT3B, and changes in the methylation status of cellular genes many of which are reported to be differentially methylated in cervical neoplasia. HPV16- and HPV18-associated changes were not randomly distributed across the genome, but clustered at specific chromosomal locations which mapped on to known HPV integration sites and to chromosomal regions lost and gained in high-grade cervical neoplasia. Methylation changes were directed in part by the same cis-acting factors that appear to direct methylation changes in cancer, the presence of a bivalent chromatin mark in human embryonic stem cells and promoter CpG content; these associations explain much of the ontological profile of genes found to have increased methylation following HPV16 transfection. We were also able to show, using sequential samples from a cohort of young women with incident HPV16 infections, that the detection in cervical samples of methylated forms of the tumour suppressor gene, RARB, often parallels the natural history of cervical HPV infection. Our findings suggest that further investigation of the distribution and determinants of early virus-induced epigenetic reprogramming will provide important insights into the pathogenesis of virus-associated malignancy.

  13. Evidence for vertical transmission of HPV from mothers to infants.

    Science.gov (United States)

    Smith, Elaine M; Parker, Michael A; Rubenstein, Linda M; Haugen, Thomas H; Hamsikova, Eva; Turek, Lubomir P

    2010-01-01

    Few large studies have evaluated concordance based on a broad spectrum of human papillomavirus (HPV) types in oral and genital specimens of mothers and their recently born infants. This information is important in determining whether HPV vaccines administered prior to pregnancy may be useful for preventing vertical transmission. HPV DNA was positive in 30% of mothers and 1.5% of newborns. Maternal/newborn concordance (HPV+/+ or HPV-/-) was 71%. Among HPV DNA+ mothers, only 3% of their infants were DNA+ and only 1 pair had the same HPV type. Among HPV- women, 0.8% of infants were HPV+. HPV DNA detected in hospitalized newborns reflects current infection transmitted to infants during pregnancy or delivery. None of the mother/baby HPV DNA+ concordance pairs detected viral types found in HPV vaccines suggesting that vaccination prior to pregnancy is unlikely to be efficacious in preventing vertical transmission.

  14. Shift in prevalence of HPV types in cervical cytology specimens in the era of HPV vaccination.

    Science.gov (United States)

    Fischer, Sonja; Bettstetter, Marcus; Becher, Andrea; Lessel, Marlene; Bank, Cyril; Krams, Matthias; Becker, Ingrid; Hartmann, Arndt; Jagla, Wolfgang; Gaumann, Andreas

    2016-07-01

    The aim of the present population-based cohort study was to analyze the association between the prevalence of 32 types of human papilloma virus (HPV) in 615 female patients with abnormal cervical cytopathology findings. In total, 32 HPV types were screened by DNA array technology. HPV infection was detected in 470 women (76.42%), 419 of whom (89.15%) were infected with ≥1 high-risk (HR)-HPV type. HPV16, which is recognized as the main HR-HPV type responsible for the development of cervical cancer, was observed in 32.98% of HPV+ participants, followed by HPV42 (18.09%), HPV31 (17.66%), HPV51 (13.83%), HPV56 (10.00%), HPV53 (8.72%) and HPV66 (8.72%). The prevalence of HR-HPV types, which may be suppressed directly (in the case of HPV16 and 18), or possibly via cross-protection (in the case of HPV31) following vaccination, was considerably lower in participants ≤22 years of age (HPV16, 28.57%; HPV18, 2.04%; HPV31, 6.12%), compared with participants 23-29 years of age (HPV16, 45.71%; HPV18, 7.86%; HPV31, 22.86%), who were less likely to be vaccinated. Consequently, the present study hypothesizes that there may be a continuous shift in the prevalence of HPV types as a result of vaccination. Furthermore, the percentage of non-vaccine HR-HPV types was higher than expected, considering that eight HPV types formerly classified as 'low-risk' or 'probably high-risk' are in fact HR-HPV types. Therefore, it may be important to monitor non-vaccine HPV types in future studies, and an investigation concerning several HR-HPV types as risk factors for the development of cervical cancer is required.

  15. Molecular characterization of p16-immunopositive but HPV DNA-negative oropharyngeal carcinomas

    NARCIS (Netherlands)

    Rietbergen, M.M.; Snijders, P.J.F.; Beekzada, D.; Braakhuis, B.J.M.; Brink, A.; Heideman, D.A.M.; Hesselink, A.T.; Witte, B.I.; Bloemena, E.; Baatenburg-de Jong, R.J.; Leemans, C.R.; Brakenhoff, R.H.

    2014-01-01

    Recent studies have reported that p16 protein overexpression qualifies as a surrogate marker identifying an oncogenic human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC). However, there is still a percentage of OPSCCs that are positive for p16 immunohistochemistry

  16. Head-to-Head Comparison of the RNA-Based Aptima Human Papillomavirus (HPV) Assay and the DNA-Based Hybrid Capture 2 HPV Test in a Routine Screening Population of Women Aged 30 to 60 Years in Germany.

    Science.gov (United States)

    Iftner, Thomas; Becker, Sven; Neis, Klaus-Joachim; Castanon, Alejandra; Iftner, Angelika; Holz, Barbara; Staebler, Annette; Henes, Melanie; Rall, Katharina; Haedicke, Juliane; von Weyhern, Claus Hann; Clad, Andreas; Brucker, Sara; Sasieni, Peter

    2015-08-01

    Testing for E6/E7 mRNA in cells infected with high-risk (HR) human papillomavirus (HPV) might improve the specificity of HPV testing for the identification of cervical precancerous lesions. Here we compared the RNA-based Aptima HPV (AHPV) assay (Hologic) and the DNA-based Hybrid Capture 2 (HC2) HPV test (Qiagen) to liquid-based cytology (LBC) for women undergoing routine cervical screening. A total of 10,040 women, 30 to 60 years of age, were invited to participate in the study, 9,451 of whom were included in the analysis. Specimens were tested centrally by LBC, the AHPV test, and the HC2 test, and women who tested positive on any test were referred for colposcopy. Genotyping was performed on all HR-HPV-positive samples. Test characteristics were calculated based on histological review. As a result, we identified 90 women with cervical intraepithelial neoplasia grade 2+ (CIN2+), including 43 women with CIN3+. Sensitivity differences between the AHPV test and the HC2 test in detecting CIN2+ (P = 0.180) or CIN3+ (P = 0.0625) lesions were statistically nonsignificant. Of three CIN3 cases that were missed with the AHPV test, two cases presented lesion-free cones and one had a non-HR HPV67 infection. The specificity (detection of high-grade precancerous lesions and may be used in primary cervical cancer screening for women ≥30 years of age. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. Reparative Spheroids in HPV-Associated Chronic Cervicitis

    National Research Council Canada - National Science Library

    Gennadiy T. Sukhikh; Tatyana A. Demura; Nafisa M. Fayzullina; Evgeniya A. Kogan

    2013-01-01

    ... chronic cervicitis (HPV-CC). Methods and Results: The cytology and biopsy materials from 223 patients with HPV-CC were subjected to molecular testing for HPV DNA by Real-Time Polymerase Chain Reaction (Real-Time PCR...

  18. HPV Test

    Science.gov (United States)

    ... detects the presence of HPV, the virus that causes cervical cancer, in your system. Certain types of HPV — including ... have any of the types of HPV that cause cervical cancer. Depending on your test results, your doctor may ...

  19. Comparison of the analytical and clinical performances of Abbott RealTime High Risk HPV, Hybrid Capture 2, and DNA Chip assays in gynecology patients.

    Science.gov (United States)

    Park, Seungman; Kang, Youjin; Kim, Dong Geun; Kim, Eui-Chong; Park, Sung Sup; Seong, Moon-Woo

    2013-08-01

    The detection of high-risk (HR) HPV in cervical cancer screening is important for early diagnosis of cervical cancer or pre-cancerous lesions. We evaluated the analytical and clinical performances of 3 HR HPV assays in Gynecology patients. A total of 991 specimens were included in this study: 787 specimens for use with a Hybrid Capture 2 (HC2) and 204 specimens for a HPV DNA microarray (DNA Chip). All specimens were tested using an Abbott RealTime High Risk HPV assay (Real-time HR), PGMY PCR, and sequence analysis. Clinical sensitivities for severe abnormal cytology (severe than high-grade squamous intraepithelial lesion) were 81.8% for Real-time HR, 77.3% for HC2, and 66.7% for DNA Chip, and clinical sensitivities for severe abnormal histology (cervical intraepithelial neoplasia grade 2+) were 91.7% for HC2, 87.5% for Real-time HR, and 73.3% for DNA Chip. As compared to results of the sequence analysis, HC2, Real-time HR, and DNA Chip showed concordance rates of 94.3% (115/122), 90.0% (117/130), and 61.5% (16/26), respectively. The HC2 assay and Real-time HR assay showed comparable results to each other in both clinical and analytical performances, while the DNA Chip assay showed poor clinical and analytical performances. The Real-time HR assay can be a good alternative option for HR HPV testing with advantages of allowing full automation and simultaneous genotyping of HR types 16 and 18. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Circulating Cell-free DNA for Metastatic Cervical Cancer Detection, Genotyping, and Monitoring.

    Science.gov (United States)

    Kang, Zhigang; Stevanović, Sanja; Hinrichs, Christian S; Cao, Liang

    2017-11-15

    Purpose: Circulating cell-free (ccf) human papillomavirus (HPV) DNA may serve as a unique tumor marker for HPV-associated malignancies, including cervical cancer. We developed a method to genotype and quantify circulating HPV DNA in patients with HPV16- or HPV18-positive metastatic cervical cancer for potential disease monitoring and treatment-related decision making.Experimental Design: In this retrospective study, HPV ccfDNA was measured in serum samples from 19 metastatic cervical cancer patients by duplex digital droplet PCR (ddPCR). Nine patients had received tumor-infiltrating lymphocyte (TIL) immunotherapy. ccfDNA data were aligned with the tumor HPV genotype, drug treatment, and clinical outcome.Results: In blinded tests, HPV ccfDNA was detected in 19 of 19 (100%) patients with HPV-positive metastatic cervical cancer but not in any of the 45 healthy blood donors. The HPV genotype harbored in the patients' tumors was correctly identified in 87 of 87 (100%) sequential patient serum samples from 9 patients who received TIL immunotherapy. In three patients who experienced objective cancer regression after TIL treatment, a transient HPV ccfDNA peak was detected 2-3 days after TIL infusion. Furthermore, persistent clearance of HPV ccfDNA was only observed in two patients who experienced complete response (CR) after TIL immunotherapy.Conclusions: HPV ccfDNA represents a promising tumor marker for noninvasive HPV genotyping and may be used in selecting patients for HPV type-specific T-cell-based immunotherapies. It may also have value in detecting antitumor activity of therapeutic agents and in the long-term follow-up of cervical cancer patients in remission. Clin Cancer Res; 23(22); 6856-62. ©2017 AACR. ©2017 American Association for Cancer Research.

  1. Clinical performance of multiplex high-risk e6 mrna expression in comparison with hpv dna subtypes for the identification of women at risk of cervical cancer.

    Science.gov (United States)

    Ho, Chih-Ming; Pan, Kui-You; Chen, Yun-Yuan; Huang, Chia-Yen; Chen, Yu-Li; Chang, Shwu-Fen

    2015-08-01

    We compared multiplex E6 messenger ribonucleic acid (mRNA) tests using real-time quantitative reverse transcriptase polymerase chain reactions (PCR) with human papillomavirus (HPV) DNA subtypes using a MY11/GP6+ PCR-based reverse-blot assay to identify cervical intraepithelial neoplasias of grade 2 or worse (CIN2+). In total, 684 women were studied, of whom 377 (55%) were diagnosed with CIN2+ histologically. The specificity of HPV mRNA to predict histological CIN2+ was higher than that of HPV DNA (81.3% vs. 44.2%). The odds ratios (ORs) to predict histological CIN2+ in women with positive for type 16, 18, 31, and 45 E6 mRNA or by HPV DNA detection were 7.1 (95% confidence interval [CI] 3.9-13.1) and 2.5 (95%CI 1.9-3.5), respectively, compared to those with negative for E6 mRNA or HPV DNA. The OR to predict histological CIN2+ in women with a cytological grade mRNA was 9.7 (95%CI 3.2-29.2), compared to those with a cytological grade mRNA (OR = 1), those with a cytological grade CIN2+, and negative for mRNA (OR = 6.9, 95%CI 4.4-10.8), and those with a cytological grade CIN2+ and positive for mRNA (OR = 28.0, 95%CI 9.8-79.6). As a HPV DNA positive triage, the OR to predict histological CIN2+ in women with a cytological grade mRNA was higher than those with negative for mRNA (OR:12.8 [95%CI 3.6-5.4] vs. OR:1.6 [95%CI 0.9-2.9]). In conclusion, multiplex HPV E6 mRNA detection can be used as a triage for women with cytological grade

  2. HPV Vaccine

    Science.gov (United States)

    ... Yourself Against HPV en español Vacuna contra el virus del papiloma humano (VPH) What Is HPV and Why Is It a Problem? Human papillomavirus (HPV) is one of the most common sexually transmitted diseases (STDs) . HPV is the virus that causes genital warts . Besides genital warts, an ...

  3. Male and Couple Fertility Impairment due to HPV-DNA Sperm Infection: Update on Molecular Mechanism and Clinical Impact—Systematic Review

    Directory of Open Access Journals (Sweden)

    Salvatore Gizzo

    2014-01-01

    Full Text Available Recent evidences identify Human Papillomavirus (HPV sperm infection as a possible cause of male and couple infertility. It acts through different mechanisms at various steps of human conception and early gestational development. We performed a systematic review to assess the role of HPV semen infection on male and couple infertility. Analysis of available and eligible data does not permit us to fund clear evidences about clinical impact of HPV infection on fertility, although sperm parameters impairment is the most widely recognized effect. Regarding biomolecular implications, the available data are often conflicting. More studies are required to define the role of HPV sperm infection in clinical practice. The great majority of evidences are obtained by in vitro studies and this fact represents a limitation for the clinical management of HPVDNA sperm infection. Understanding the biological significance of HPV-DNA semen infection could permit us to explain most of the idiopathic male and couple infertility, leading to a better management of infertile men and a better timing for sperm banking storage before ART cycles.

  4. Male and couple fertility impairment due to HPV-DNA sperm infection: update on molecular mechanism and clinical impact--systematic review.

    Science.gov (United States)

    Gizzo, Salvatore; Ferrari, Bruno; Noventa, Marco; Ferrari, Emanuele; Patrelli, Tito Silvio; Gangemi, Michele; Nardelli, Giovanni Battista

    2014-01-01

    Recent evidences identify Human Papillomavirus (HPV) sperm infection as a possible cause of male and couple infertility. It acts through different mechanisms at various steps of human conception and early gestational development. We performed a systematic review to assess the role of HPV semen infection on male and couple infertility. Analysis of available and eligible data does not permit us to fund clear evidences about clinical impact of HPV infection on fertility, although sperm parameters impairment is the most widely recognized effect. Regarding biomolecular implications, the available data are often conflicting. More studies are required to define the role of HPV sperm infection in clinical practice. The great majority of evidences are obtained by in vitro studies and this fact represents a limitation for the clinical management of HPVDNA sperm infection. Understanding the biological significance of HPV-DNA semen infection could permit us to explain most of the idiopathic male and couple infertility, leading to a better management of infertile men and a better timing for sperm banking storage before ART cycles.

  5. Male and Couple Fertility Impairment due to HPV-DNA Sperm Infection: Update on Molecular Mechanism and Clinical Impact—Systematic Review

    Science.gov (United States)

    Gizzo, Salvatore; Ferrari, Bruno; Noventa, Marco; Ferrari, Emanuele; Patrelli, Tito Silvio; Gangemi, Michele; Nardelli, Giovanni Battista

    2014-01-01

    Recent evidences identify Human Papillomavirus (HPV) sperm infection as a possible cause of male and couple infertility. It acts through different mechanisms at various steps of human conception and early gestational development. We performed a systematic review to assess the role of HPV semen infection on male and couple infertility. Analysis of available and eligible data does not permit us to fund clear evidences about clinical impact of HPV infection on fertility, although sperm parameters impairment is the most widely recognized effect. Regarding biomolecular implications, the available data are often conflicting. More studies are required to define the role of HPV sperm infection in clinical practice. The great majority of evidences are obtained by in vitro studies and this fact represents a limitation for the clinical management of HPVDNA sperm infection. Understanding the biological significance of HPV-DNA semen infection could permit us to explain most of the idiopathic male and couple infertility, leading to a better management of infertile men and a better timing for sperm banking storage before ART cycles. PMID:24783196

  6. Malignant progression of laryngeal papilloma associated with human papilloma virus type 6 (HPV-6) DNA.

    Science.gov (United States)

    Zarod, A P; Rutherford, J D; Corbitt, G

    1988-01-01

    A case of laryngeal squamous papilloma in the early stages of development showed histological features suggestive of virus infection. Five years later positive evidence of HPV-6 infection was obtained at a time when the lesion had developed into a squamous cell carcinoma. It is concluded that this case represents a complete example of the virus to papilloma to carcinoma sequence, and as far as is known, is the first reported case of its kind in the larynx. Images Fig 1 Fig 2 Fig 3 Fig 4 PMID:2834418

  7. High genital prevalence of cutaneous human papillomavirus DNA on male genital skin: the HPV Infection in Men Study.

    Science.gov (United States)

    Sichero, Laura; Pierce Campbell, Christine M; Fulp, William; Ferreira, Silvaneide; Sobrinho, João S; Baggio, Maria; Galan, Lenice; Silva, Roberto C; Lazcano-Ponce, Eduardo; Giuliano, Anna R; Villa, Luisa L

    2014-12-09

    The genital skin of males hosts a diversity of HPV genotypes and uncharacterized HPV genotypes. Previously we demonstrated that a specific viral genotype was not identified in 14% of all genital specimens (i.e., HPV unclassified specimens) using the Roche Linear Array method. Our goal was to identify and assess the prevalence of individual HPV types among genital HPV unclassified specimens collected in the HIM Study population, at enrollment, and examine associations with socio-demographic and behavioral characteristics. Genital skin specimens of men that were considered unclassified (HPV PCR positive, no genotype specified) at enrollment were typed by sequencing amplified PGMY09/11 products or cloning of PGMY/GP+ nested amplicons followed by sequencing. PGMY/GP+ negative specimens were further analyzed using FAP primers. HPV type classification was conducted through comparisons with sequences in the GenBank database. Readable nucleotide sequences were generated for the majority of previously unclassified specimens (66%), including both characterized (77%) and yet uncharacterized (23%) HPV types. Of the characterized HPV types, most (73%) were Beta [β]-HPVs, primarily from β-1 and β-2 species, followed by Alpha [α]-HPVs (20%). Smokers (current and former) were significantly more likely to have an α-HPV infection, compared with any other genus; no other factors were associated with specific HPV genera or specific β-HPV species. Male genital skin harbor a large number of β-HPV types. Knowledge concerning the prevalence of the diverse HPV types in the men genital is important to better understand the transmission of these viruses.

  8. Development and Characterization of an HPV Type-16 Specific Modified DNA Aptamer for the Improvement of Potency Assays.

    Science.gov (United States)

    Trausch, Jeremiah J; Shank-Retzlaff, Mary; Verch, Thorsten

    2017-03-21

    Measuring vaccine potency is critical for vaccine release and is often accomplished using antibody-based ELISAs. Antibodies can be associated with significant drawbacks that are often overlooked including lot-to-lot variability, problems with cell-line maintenance, limited stability, high cost, and long discovery lead times. Here, we address many of these issues through the development of an aptamer, known as a slow off-rate modified DNA aptamer (SOMAmer), which targets a vaccine antigen in the human papillomavirus (HPV) vaccine Gardasil. The aptamer, termed HPV-07, was selected to bind the Type 16 virus-like-particle (VLP) formed by the self-assembling capsid protein L1. It is capable of binding with high sensitivity (EC50 of 0.1 to 0.4 μg/mL depending on assay format) while strongly discriminating against other VLP types. The aptamer competes for binding with the neutralizing antibody H16.V5, indicating at least partial recognition of a neutralizing and clinically relevant epitope. This makes it a useful reagent for measuring both potency and stability. When used in an ELISA format, the aptamer displays both high precision (intermediate precision of 6.3%) and a large linear range spanning from 25% to 200% of a typical formulation. To further exploit the advantages of aptamers, a simplified mix and read assay was also developed. This assay format offers significant time and resource reductions compared to a traditional ELISA. These results show aptamers are suitable reagents for biological potency assays, and we expect that their implementation could improve upon current assay formats.

  9. Comparison of the Abbott RealTime High-Risk Human Papillomavirus (HPV), Roche Cobas HPV, and Hybrid Capture 2 assays to direct sequencing and genotyping of HPV DNA.

    Science.gov (United States)

    Park, Yongjung; Lee, Eunhee; Choi, Jonghyeon; Jeong, Seri; Kim, Hyon-Suk

    2012-07-01

    Infection with high-risk (HR) human papillomavirus (HPV) genotypes is an important risk factor for cervical cancers. We evaluated the clinical performances of two new real-time PCR assays for detecting HR HPVs compared to that of the Hybrid Capture 2 test (HC2). A total of 356 cervical swab specimens, which had been examined for cervical cytology, were assayed by Abbott RealTime HR and Roche Cobas HPV as well as HC2. Sensitivities and specificities of these assays were determined based on the criteria that concordant results among the three assays were regarded as true-positive or -negative and that the results of genotyping and sequencing were considered true findings when the HPV assays presented discrepant results. The overall concordance rate among the results for the three assays was 82.6%, and RealTime HR and Cobas HPV assays agreed with HC2 in 86.1% and 89.9% of cases, respectively. The two real-time PCR assays agreed with each other for 89.6% of the samples, and the concordance rate between them was equal to or greater than 98.0% for detecting HPV type 16 or 18. HC2 demonstrated a sensitivity of 96.6% with a specificity of 89.1% for detecting HR HPVs, while RealTime HR presented a sensitivity of 78.3% with a specificity of 99.2%. The sensitivity and specificity of Cobas HPV for detecting HR HPVs were 91.7% and 97.0%. The new real-time PCR assays exhibited lower sensitivities for detecting HR HPVs than that of HC2. Nevertheless, the newly introduced assays have an advantage of simultaneously identifying HPV types 16 and 18 from clinical samples.

  10. Developing Inhibitors of Translesion DNA Synthesis as Therapeutic Agents against Lung Cancer

    Science.gov (United States)

    2015-12-01

    AWARD NUMBER: W81XWH-13-1-0238 TITLE: Developing Inhibitors of Translesion DNA Synthesis as Therapeutic Agents against Lung Cancer PRINCIPAL...of Translesion DNA Synthesis as Therapeutic Agents against Lung Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...Oxygen-rich environments can create pro- mutagenic DNA lesions such as 8-oxoguanine (8-oxo-G) that can be misreplicated during translesion DNA synthesis

  11. HPV-DNA sperm infection and infertility: from a systematic literature review to a possible clinical management proposal.

    Science.gov (United States)

    Foresta, C; Noventa, M; De Toni, L; Gizzo, S; Garolla, A

    2015-03-01

    The objectives of this study were to investigate the implications of human papillomavirus (HPV) sperm infection on male fertility, impairment of sperm parameters, and possible alteration of sperm nuclear status and to identify a possible effective management of infertile men with HPV sperm infection. We employed a systematic review and clinical management proposal at the Centers for Reproductive and Health care for treating infertile male patients with HPV infection. Literature search was carried out in electronic databases in the last two decades. We focused our attention on: (i) HPV sperm prevalence (ii) HPV-related alteration of sperm parameters; (iii) molecular mechanisms of HPV semen infection and infertility. The main outcome measures were HPV prevalence in infertile male patients and semen parameters. The prevalence of HPV sperm infection ranges between 2 and 31% in men from general population and between 10 and 35.7% in men affected by unexplained infertility. The presence of HPV in semen is associated with an impairment of sperm motility and the presence of anti-sperm antibodies. The molecular mechanisms underlying impairment of sperm motility apparatus need further evaluations. A greater attention should be applied to assess HPV sperm infection, particularly in men undergoing assisted reproduction techniques cycle for male infertility or sperm banking. It would be useful to perform HPV test and fluorescent in situ hybridization analysis for HPV in semen from these patients both at first admission, to define the possible presence and localization of semen infection, and after 6 months, to assess the possible virus clearance retrieval on normal sperm parameters. © 2014 American Society of Andrology and European Academy of Andrology.

  12. Genital Warts (HPV)

    Science.gov (United States)

    ... Growth Problems Cervical Cap HPV Vaccine Genital Warts (HPV) KidsHealth > For Teens > Genital Warts (HPV) Print A ... HPV infection. How Do People Know They Have HPV? Most HPV infections have no signs or symptoms. ...

  13. Comparison of the Abbott RealTime High-Risk Human Papillomavirus (HPV), Roche Cobas HPV, and Hybrid Capture 2 Assays to Direct Sequencing and Genotyping of HPV DNA

    OpenAIRE

    Park, Yongjung; Lee, Eunhee; Choi, Jonghyeon; Jeong, Seri; Kim, Hyon-Suk

    2012-01-01

    Infection with high-risk (HR) human papillomavirus (HPV) genotypes is an important risk factor for cervical cancers. We evaluated the clinical performances of two new real-time PCR assays for detecting HR HPVs compared to that of the Hybrid Capture 2 test (HC2). A total of 356 cervical swab specimens, which had been examined for cervical cytology, were assayed by Abbott RealTime HR and Roche Cobas HPV as well as HC2. Sensitivities and specificities of these assays were determined based on the...

  14. Comparison of different methods for extraction and purification of human Papillomavirus (HPV) DNA from serum samples

    Science.gov (United States)

    Azizah, N.; Hashim, U.; Nadzirah, Sh.; Arshad, M. K. Md; Ruslinda, A. R.; Gopinath, Subash C. B.

    2017-03-01

    The affectability and unwavering quality of PCR for indicative and research purposes require effective fair systems of extraction and sanitization of nucleic acids. One of the real impediments of PCR-based tests is the hindrance of the enhancement procedure by substances exhibit in clinical examples. This examination considers distinctive techniques for extraction and cleaning of viral DNA from serum tests in view of recuperation productivity as far as yield of DNA and rate recouped immaculateness of removed DNA, and rate of restraint. The best extraction strategies were the phenol/chloroform strategy and the silica gel extraction methodology for serum tests, individually. Considering DNA immaculateness, extraction technique by utilizing the phenol/chloroform strategy delivered the most tasteful results in serum tests contrasted with the silica gel, separately. The nearness of inhibitors was overcome by all DNA extraction strategies in serum tests, as confirm by semiquantitative PCR enhancement.

  15. DNA damage response and cancer therapeutics through the lens of the Fanconi Anemia DNA repair pathway.

    Science.gov (United States)

    Bhattacharjee, Sonali; Nandi, Saikat

    2017-10-10

    Fanconi Anemia (FA) is a rare, inherited genomic instability disorder, caused by mutations in genes involved in the repair of interstrand DNA crosslinks (ICLs). The FA signaling network contains a unique nuclear protein complex that mediates the monoubiquitylation of the FANCD2 and FANCI heterodimer, and coordinates activities of the downstream DNA repair pathway including nucleotide excision repair, translesion synthesis, and homologous recombination. FA proteins act at different steps of ICL repair in sensing, recognition and processing of DNA lesions. The multi-protein network is tightly regulated by complex mechanisms, such as ubiquitination, phosphorylation, and degradation signals that are critical for the maintenance of genome integrity and suppressing tumorigenesis. Here, we discuss recent advances in our understanding of how the FA proteins participate in ICL repair and regulation of the FA signaling network that assures the safeguard of the genome. We further discuss the potential application of designing small molecule inhibitors that inhibit the FA pathway and are synthetic lethal with DNA repair enzymes that can be used for cancer therapeutics.

  16. HPV detection in oral carcinomas

    Directory of Open Access Journals (Sweden)

    Vidal Aurora Karla de Lacerda

    2004-01-01

    Full Text Available The authors set out in this study to verify the presence of low- and high-risk DNA of human papillomavirus (HPV in oral cancer by means of the hybrid capture Digene® test (São Paulo-SP, Brazil in smears from exfoliative cytology and also to compare the findings with those of conventional light microscopy (hematoxylin-eosin (HE/Papanicolaou. Forty individuals gave their written informed consent to participate in the study and also had their clinical data analyzed. The 40 exfoliative cytology examinations performed to date produced the following results: 29 (72.5% negative for low- and high-risk HPV-DNA; nine (22.5% positive for low- and high-risk HPV-DNA; one (2.5% positive for low-risk HPV-DNA; and one (2.5% positive for high-risk HPV-DNA. There was agreement among the findings for the presence of DNA-HPV for both exfoliative cytology (smear to hybrid capture Digene® test and the cytological smear readings made by conventional light microscopy. It was therefore concluded that the HPV virus may be a cocarcinogen of the mouth cancer as it is in the cervix cancer.

  17. LALF32-51 -E7, a HPV-16 therapeutic vaccine candidate, forms protein body-like structures when expressed in Nicotiana benthamiana leaves.

    Science.gov (United States)

    Yanez, Romana J R; Lamprecht, Renate; Granadillo, Milaid; Torrens, Isis; Arcalís, Elsa; Stöger, Eva; Rybicki, Edward P; Hitzeroth, Inga I

    2017-07-22

    High-risk human papillomaviruses (HPVs) cause cervical cancer, and while there are good prophylactic vaccines on the market, these are ineffective against established infections, creating a clear need for therapeutic vaccines. The HPV E7 protein is one of the essential oncoproteins for the onset and maintenance of malignancy and is therefore an ideal therapeutic vaccine target. We fused the HPV-16 E7 protein to the Limulus polyphemus antilipopolysaccharide factor (LALF32-51 ), a small hydrophobic peptide that can penetrate cell membranes and that has immunomodulatory properties. LALF32-51 -E7 was transiently expressed in Nicotiana benthamiana, and we previously determined that it accumulated better when targeted to chloroplasts compared to being localized in the cytoplasm. Subsequently, we aimed to prove whether LALF32-51 -E7 was indeed associated with the chloroplasts by determining its subcellular localization. The LALF32-51 -E7 gene was fused to one encoding enhanced GFP to generate a LG fusion protein, and localization was determined by confocal laser scanning microscopy and transmission electron microscopy (TEM). The fluorescence observed from chloroplast-targeted LG was distinctively different from that of the cytoplasmic LG. Small spherical structures resembling protein bodies (PBs) were seen that clearly localized with the chloroplasts. Larger but less abundant PB-like structures were also seen for the cytoplasmic LG. PB-like structure formation was confirmed for both LG and LALF32-51 -E7 by TEM. LALF32-51 -E7 was indeed targeted to the chloroplasts by the chloroplast transit peptide used in this study, and it formed aggregated PB-like structures. This study could open a new avenue for the use of LALF32-51 as a PB-inducing peptide. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  18. High prevalence of oncogenic HPV-16 in cervical smears of ...

    Indian Academy of Sciences (India)

    Significant association of HPV with non-vegetarian diet ( < 0.05) and rural residential areas ( < 0.01) were observed. High prevalence of HPV-16 in asymptomatic women of this population, a frequency comparable to invasive cervical cancers, highlights an urgent need for a therapeutic HPV vaccine covering HPV-16 and ...

  19. High HPV infection prevalence in men from infertile couples and lack of relationship between seminal HPV infection and sperm quality.

    Science.gov (United States)

    Golob, Barbara; Poljak, Mario; Verdenik, Ivan; Kolbezen Simoniti, Mojca; Vrtačnik Bokal, Eda; Zorn, Branko

    2014-01-01

    Human papillomaviruses (HPV) are the most frequently sexually transmitted viruses and etiological agents of several human cancers. Controversial results of the role of HPV in infertile population on sperm parameters have been published. The aim of this study was to estimate the type-specific prevalence of HPV DNA infection of the external genitalia and semen in 340 Slovenian men from infertile couples and to establish the relationship between seminal HPV DNA infection and abnormal sperm parameters. Self-taken swabs of the entire penile surface and semen samples were collected, and HPV detection and genotyping were performed. HPV DNA was detected in 37.12% of external genitalia and in 13.61% of semen samples with high HPV type concordance of both sampling sites. The most prevalent HPV types in the male external genitalia were HPV-CP6108 and HPV-84. The most prevalent HPV types in semen were HPV-53 and HPV-CP6108. The prevalence of HPV infection between normozoospermic men and men with abnormal sperm parameters did not differ significantly. Sperm quality did not differ significantly between men with seminal HPV infection and uninfected men. In conclusion, the men from infertile couples are equally susceptible to HPV infection regardless of their fertile potential; seminal HPV infection does not impair sperm quality.

  20. High HPV Infection Prevalence in Men from Infertile Couples and Lack of Relationship between Seminal HPV Infection and Sperm Quality

    Directory of Open Access Journals (Sweden)

    Barbara Golob

    2014-01-01

    Full Text Available Human papillomaviruses (HPV are the most frequently sexually transmitted viruses and etiological agents of several human cancers. Controversial results of the role of HPV in infertile population on sperm parameters have been published. The aim of this study was to estimate the type-specific prevalence of HPV DNA infection of the external genitalia and semen in 340 Slovenian men from infertile couples and to establish the relationship between seminal HPV DNA infection and abnormal sperm parameters. Self-taken swabs of the entire penile surface and semen samples were collected, and HPV detection and genotyping were performed. HPV DNA was detected in 37.12% of external genitalia and in 13.61% of semen samples with high HPV type concordance of both sampling sites. The most prevalent HPV types in the male external genitalia were HPV-CP6108 and HPV-84. The most prevalent HPV types in semen were HPV-53 and HPV-CP6108. The prevalence of HPV infection between normozoospermic men and men with abnormal sperm parameters did not differ significantly. Sperm quality did not differ significantly between men with seminal HPV infection and uninfected men. In conclusion, the men from infertile couples are equally susceptible to HPV infection regardless of their fertile potential; seminal HPV infection does not impair sperm quality.

  1. The specifities of the HPV-genital infections in males

    Directory of Open Access Journals (Sweden)

    Mihael Skerlev

    2010-08-01

    Full Text Available Anogenital infections caused by Human papillomavirus (HPV are the most frequently diagnosed sexually transmitted infections of viral origin and up to 150 HPV DNA types have been recognized so far. Anogenital warts (condylomata acuminata are the most common lesions presented in men, however, during the last decade the other HPV-associated exaggerated lesions such as condylomata plana, penile,scrotal, and anal intraepithelial neoplasias, as well as the penile, urine bladder and prostate cancer have been studied somewhat more extensively. The clinical variations might range from clinically invisible, asymptomatic lesions to the bizarre forms of giant condyloma of Buschke-Löwenstein type, including Bowenoid papulosis,Mb. Bowen, different kinds of eryhtroplasia both in men and women and a large spectrum of HPV-induced dermatovenereological entities in genital region including high-grade intraepithelial genital neoplasias, such as penile, anal, scrotal, vulvar, vaginal etc. (thus not only cervical, and, last but not least - the anogenital warts. A prophylactic vaccine that targets these types should thus substantially reduce the burden of HPV-associated clinical diseases. Ultimately, within the spectrum of therapeutic options for condylomata, no method is really superior to others; recurrences occurred in 30-70% of cases. We definitely need the HPV vaccination programme to eliminate one of the oldest and up to now unsolved problems of the mankind. Since HPV is transmitted by sexual intercourse, treatment of both partners is necessary in order to eliminate the virus from the population. Approaches to this include prophylactic vaccines such as quadrivalent HPV vaccine for both men and women

  2. Correlation between HPV sperm infection and male infertility.

    Science.gov (United States)

    Yang, Yang; Jia, Chan-Wei; Ma, Yan-Min; Zhou, Li-Ying; Wang, Shu-Yu

    2013-07-01

    Human papillomavirus (HPV) is one of the most common sexually transmitted diseases which comprises a group of small DNA viruses that infect both cutaneous and mucous squamous epithelia. Liquid bead microarray technology (LBMA) were used to evaluate 24 HPV genotypes in confirmed fertile and infertile males of North China so that the effects of HPV infection on semen parameters and relationship with male infertility could be discussed. A total of 1138 subjects were recruited in this study; 142 were HPV-positive (12.48%). Among 523 confirmed fertile males, only 35 were HPV-positive (6.70%), and two of them had multiple infections. Among 615 infertile males, 107 were HPV-positive (17.4%), and 29 of them had multiple infections. Infertile males had a relatively high HPV infection rate compared with confirmed fertile males. Sperm progressive motility (PR) and the normal morphology rate were significantly decreased in HPV-positive subjects. HPV-45, HPV-52, HPV-18, HPV-59 and HPV-16 infections were more frequently in infertile males. Hence, HPV infection is closely related to male infertility which will decrease sperm PR and morphology. HPV-45, HPV-52, HPV-18, HPV-59 and HPV-16 infection seems to be major risk factors.

  3. The positivity for human papillomavirus (HPV DNA and evaluation of probable risk factors among women in Eskisehir region

    Directory of Open Access Journals (Sweden)

    Ferhat Gurkan Aslan

    2015-06-01

    Conclusions: In addition to the prevention of cervical cancer, scanning programs are also important in protection against HPV infection. Applications which could be implemented on this subject can be considered as defining the potential risk factors and taking precautions against them. More detailed studies should be conducted in Turkey to research the relationship between HPV infections and social groups, the frequency of HPV infection,results, follow-up, treatment, control and prevention. Communities must be made aware of this subject throughpublic health education. [TAF Prev Med Bull 2015; 14(3.000: 222-228

  4. Molecular events leading to HPV-induced high grade neoplasia

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    Saskia M. Wilting

    2016-12-01

    Full Text Available Cervical cancer is initiated by high-risk types of the human papillomavirus (hrHPV and develops via precursor stages, called cervical intraepithelial neoplasia (CIN. High-grade CIN lesions are considered true precancerous lesions when the viral oncogenes E6 and E7 are aberrantly expressed in the dividing cells. This results in abolishment of normal cell cycle control via p53 and pRb degradation. However, it has become clear that these viral oncogenes possess additional oncogenic properties, including interference with the DNA methylation machinery and mitotic checkpoints. Identification of the resulting molecular events leading to high-grade neoplasia will 1 increase our understanding of cervical carcinogenesis, 2 yield biomarkers for early diagnosis, and 3 identify therapeutic targets for HPV-induced (pre cancerous lesions.This review will briefly summarise current advances in our understanding of the molecular alterations in the host cell genome that occur during HPV-induced carcinogenesis.

  5. Shift in prevalence of HPV types in cervical cytology specimens in the era of HPV vaccination

    OpenAIRE

    Fischer, Sonja; Bettstetter, Marcus; BECHER, ANDREA; LESSEL, MARLENE; BANK, CYRIL; Krams, Matthias; Becker, Ingrid; Hartmann, Arndt; Jagla, Wolfgang; Gaumann, Andreas

    2016-01-01

    The aim of the present population-based cohort study was to analyze the association between the prevalence of 32 types of human papilloma virus (HPV) in 615 female patients with abnormal cervical cytopathology findings. In total, 32 HPV types were screened by DNA array technology. HPV infection was detected in 470 women (76.42%), 419 of whom (89.15%) were infected with ≥1 high-risk (HR)-HPV type. HPV16, which is recognized as the main HR-HPV type responsible for the development of cervical ca...

  6. The Need for Cervical Cancer Control in HIV-Positive and HIV-Negative Women from Romania by Primary Prevention and by Early Detection Using Clinically Validated HPV/DNA Tests.

    Directory of Open Access Journals (Sweden)

    Ramona Gabriela Ursu

    Full Text Available In Romania, a country with no organized national surveillance program regarding cervical cancer, the early diagnosis of HPV (Human Papilloma Virus infections is a major requirement, especially in HIV-infected women. The objective of this study was to determine the HPV prevalence and type distribution in young HIV-positive women and to assess the difference in the risk factors for developing cervical cancer compared to those of HIV-negative women.We conducted one cross-sectional cohort study from June 2013-September 2014, including 1,032 women: 992 HIV- women who were 36.5 years old (limits: 17 ÷ 84 and 40 HIV + women who were 22.9 years old (limits: 17 ÷ 30 with iatrogenic HIV infected. We detected HPV types with the Linear Array HPV Genotyping test (Roche, Romania.DNA/HPV was detected in 18/40 (45% of the HIV+ patients and in 350/992 (35.2% of the HIV- patients (OR = 1.5, 95%CI 0.76÷2.96. After age adjustment, the overall HPV prevalence was 51.6% in HIV+ versus 63.2% in HIV- women aged under 25, and 22.2% in HPV+ versus 47.2% in HIV- women aged 25-34. We detect HIV being a risk factor for acquiring multiple HPV type infections (OR = 2.30, 95% CI 0.88÷5.97. The eight most common HPV types (high-risk, and low-risk for women below age 30, HIV+ / - were: HPV 16, 18, 31, 51, 58, 68, and 6 and 82 respectively. To assess the risk factors of HIV-positive women for acquiring HPV infection, we analyzed the CD4/μL, ARN/HIV copies/μL, the age group, the number of sexual partners, smoking, and the type of HPV infection (single versus multiple infections. We found that the number of sexual partners and smoking are statistically significant risk factors.Even though there are no significant differences regarding the prevalence of HPV infection in HIV + versus HIV - patients, multiple infections were more frequent in the first group. In our study group young HIV-infected patients under HAART therapy, high number of sexual partners (more than 3 and smoking

  7. Identification of HPV variants.

    Science.gov (United States)

    Cason, John; Bible, Jon; Mant, Christine

    2005-01-01

    The vast majority of anogenital carcinomas are caused by high-risk human papillomaviruses (HPVs), and among Western nations HPV-16 is usually the most predominant cancer-associated type. As a DNA virus, HPV type 16 has a relatively stable genome that is believed to have co-evolved with its host over the millennia. Nevertheless, among the "wild" populations of HPV-16 that are circulating, a large number of variants have been identified, and these may have considerably different pathogenic potentials. In this chapter, methods for screening and characterizing HPV-16 sequence variants are described. In particular, we describe methods for the identification of variation within the HPV-16 E5 open reading frame and for the detection of the nt 131 A-->G mutation of the E6 ORF, using restriction fragment length polymorphism assays. In addition, we describe approaches for DNA sequencing and analysis. Such methods are likely to be of particular interest to those involved in epidemiological investigations of virus transmission and pathogenicity studies.

  8. Concordance of HPV load and HPV mRNA for 16 carcinogenic/possibly carcinogenic HPV types in paired smear/tissue cervical cancer specimens.

    Science.gov (United States)

    Halec, Gordana; Dondog, Bolormaa; Pawlita, Michael; Schmitt, Markus

    2017-11-01

    HPV types with high viral load are associated with cervical abnormalities. However, viral load measurements and concordance of HPV loads and viral mRNA have not been demonstrated for all high-risk/possibly high-risk (HR-/pHR-)HPV types in cervical cancer (CxCa). Especially, the biological role of co-infecting HR-/pHR-HPV types with low viral load has not been thoroughly investigated. Using BSGP5+/6+-PCR/MPG genotyping, we analyzed viral loads for all currently defined 51 mucosal HPV types in 74 cervical smears from patients with CxCa and compared this data with HPV DNA and mRNA status in these patients' corresponding CxCa tissues. All cervical smear/tissue pairs were HPV DNA+. Overall HPV type agreement within pairs was 99% (complete agreement in 50%, partial agreement in 49%, and complete disagreement in 1% of cases). The proportion of multiple HPV types was significantly higher in smears compared to tissues (pHPV infections (>1 copy/cell) were found in 88% of HPV DNA+ smears, and were significantly associated with the presence of respective HPV DNA (kappa=0.685, CI: 0.567-0.803), and HPV mRNA (kappa=0.693, CI: 0.566-0.820) in CxCa tissues. In total, 93% (67/72) of high load HR-/pHR-HPV infections identified in smears were also present in corresponding CxCa tissues, and 93% (62/67) of these were HPV mRNA+. On the other hand, 78% (42/54) of low load HR-/pHR-HPV infections identified in smears were not detectable in tissues, including 11 out of 15 low load HPV16 infections. This data demonstrates that the presence of high HPV loads in CxCa smears predicts biologically active HR-/pHR-HPV types in tumor tissues.

  9. A comparison of methylation levels in HPV18, HPV31 and HPV33 genomes reveals similar associations with cervical precancers.

    Science.gov (United States)

    Vasiljević, Nataša; Scibior-Bentkowska, Dorota; Brentnall, Adam; Cuzick, Jack; Lorincz, Attila

    2014-03-01

    High risk human papillomavirus (HR-HPV) infection is common and only a small minority of infections become persistent and lead to cervical cancers. Women positive for HR-HPV usually require a second test to avoid unnecessary colposcopies and over treatment. Elevated DNA methylation of HR-HPV L1 and L2 genes in high grade disease has emerged as a promising molecular triage tool. Our aim was to accurately measure methylation levels at selected CpG positions in the HPV18, HPV31 and HPV33 genomes. We focused on the L2, L1, URR and E6 regions because these were previously shown to be interesting areas for study. Pyrosequencing was used to measure methylation in 208 HPV18, 207 HPV31, and 126 HPV33 positive women selected from a London colposcopy referral population. After adjustment for multiple testing, at FDR 5%, elevated methylation was significantly associated with cervical intraepithelial neoplasia grades 2 or worse (CIN2+) in all investigated CpGs in HPV18 L2 and L1. Two of 6 L2 and 12 of 15 L1 sites in HPV31 and 6 of 8 L2 and 3 of 13 L1 sites in HPV33 showed significantly elevated methylation in CIN2+. Methylation of CpG sites in the URR and E6 region of the HPV types was low and most differences were not significant. Elevated methylation of CpG sites in the L1 and L2 regions of HPV18, HPV31 and HPV33 is associated with CIN2+ and a panel test may be useful for triage of women with HR-HPV infections. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  10. HPV16 DNA status is a strong prognosticator of loco-regional control after postoperative radiochemotherapy of locally advanced oropharyngeal carcinoma: results from a multicentre explorative study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG).

    Science.gov (United States)

    Lohaus, Fabian; Linge, Annett; Tinhofer, Inge; Budach, Volker; Gkika, Eleni; Stuschke, Martin; Balermpas, Panagiotis; Rödel, Claus; Avlar, Melanie; Grosu, Anca-Ligia; Abdollahi, Amir; Debus, Jürgen; Bayer, Christine; Belka, Claus; Pigorsch, Steffi; Combs, Stephanie E; Mönnich, David; Zips, Daniel; von Neubeck, Cläre; Baretton, Gustavo B; Löck, Steffen; Thames, Howard D; Krause, Mechthild; Baumann, Michael

    2014-12-01

    To investigate the impact of HPV status in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received surgery and cisplatin-based postoperative radiochemotherapy. For 221 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity treated at the 8 partner sites of the German Cancer Consortium, the impact of HPV DNA, p16 overexpression and p53 expression on outcome were retrospectively analysed. The primary endpoint was loco-regional tumour control; secondary endpoints were distant metastases and overall survival. In the total patient population, univariate analyses revealed a significant impact of HPV16 DNA positivity, p16 overexpression, p53 positivity and tumour site on loco-regional tumour control. Multivariate analysis stratified for tumour site showed that positive HPV 16 DNA status correlated with loco-regional tumour control in patients with oropharyngeal carcinoma (p=0.02) but not in the oral cavity carcinoma group. Multivariate evaluation of the secondary endpoints in the total population revealed a significant association of HPV16 DNA positivity with overall survival (ploco-regional tumour control after postoperative cisplatin-based radiochemotherapy of locally advanced oropharyngeal carcinoma and is now being explored in a prospective validation trial. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Prevalence of human papillomavirus (HPV) and HPV-16 genotyping by real-time PCR in patients with several cervical pathologies.

    Science.gov (United States)

    Dinc, Bedia; Rota, Seyyal; Onan, Anil; Bozdayi, Gulendam; Taskiran, Cagatay; Biri, Aydan; Güner, Haldun

    2010-01-01

    this study was planned to evaluate the prevalence of HPV (excepting type 16) and HPV 16 by real-time PCR in colposcopy patients and to interprete the results with age, age of first sexual intercourse (FSI), parity and Pap smear results. one hundred and two colposcopy patients (50 and 52 of the patients were classified as colposcopy positive and negative, respectively) applying to Gynecology clinic were included. HPV (excepting type 16) and HPV 16 were detected by realtime PCR using the L1 region. Real-time nested amplifications of MY09/11 products were done by GP5+/GP6+ primers and Cyanine-5 labeled HPV and HPV 16 DNA specific probe after HPV DNA extraction by phenol chloroform isoamylalcohol. HPV (excepting type 16) and HPV 16 were positive in 12% and 18% of the colposcopy positive patients respectively. HPV (excepting type 16) and HPV 16 were positive in 5.7% and 3.8% of the colposcopy negative patients, respectively. there was a statistically significant difference between colposcopy positive and colposcopy negative patients comparing HPV 16 with total HPV positivity (p = 0.021 for type 16 and p = 0.010 for total HPV) but there was not a statistically significant difference between colposcopy positive and colposcopy negative patients when we compared HPV (excepting type 16) positivity (p = 0.314). In conclusion, HPV detection and typing may be helpful for cervical cancer screening and prevention.

  12. Prevalence of human papillomavirus (HPV and HPV-16 genotyping by real-time PCR in patients with several cervical pathologies

    Directory of Open Access Journals (Sweden)

    Bedia Dinc

    Full Text Available PURPOSE: this study was planned to evaluate the prevalence of HPV (excepting type 16 and HPV 16 by real-time PCR in colposcopy patients and to interprete the results with age, age of first sexual intercourse (FSI, parity and Pap smear results. METHODS: one hundred and two colposcopy patients (50 and 52 of the patients were classified as colposcopy positive and negative, respectively applying to Gynecology clinic were included. HPV (excepting type 16 and HPV 16 were detected by realtime PCR using the L1 region. Real-time nested amplifications of MY09/11 products were done by GP5+/GP6+ primers and Cyanine-5 labeled HPV and HPV 16 DNA specific probe after HPV DNA extraction by phenol chloroform isoamylalcohol. RESULTS: HPV (excepting type 16 and HPV 16 were positive in 12% and 18% of the colposcopy positive patients respectively. HPV (excepting type 16 and HPV 16 were positive in 5.7% and 3.8% of the colposcopy negative patients, respectively. CONCLUSION: there was a statistically significant difference between colposcopy positive and colposcopy negative patients comparing HPV 16 with total HPV positivity (p = 0.021 for type 16 and p = 0.010 for total HPV but there was not a statistically significant difference between colposcopy positive and colposcopy negative patients when we compared HPV (excepting type 16 positivity (p = 0.314. In conclusion, HPV detection and typing may be helpful for cervical cancer screening and prevention.

  13. Chromogenic In Situ Hybridization and p16/Ki67 Dual Staining on Formalin-Fixed Paraffin-Embedded Cervical Specimens: Correlation with HPV-DNA Test, E6/E7 mRNA Test, and Potential Clinical Applications

    Directory of Open Access Journals (Sweden)

    Roberta Zappacosta

    2013-01-01

    Full Text Available Although HPV-DNA test and E6/E7 mRNA analyses remain the current standard for the confirmation of human papillomavirus (HPV infections in cytological specimens, no universally adopted techniques exist for the detection of HPV in formalin-fixed paraffin-embedded samples. Particularly, in routine laboratories, molecular assays are still time-consuming and would require a high level of expertise. In this study, we investigated the possible use of a novel HPV tyramide-based chromogenic in situ hybridization (CISH technology to locate HPV on tissue specimens. Then, we evaluate the potential usefulness of p16INK4a/Ki-67 double stain on histological samples, to identify cervical cells expressing HPV E6/E7 oncogenes. In our series, CISH showed a clear signal in 95.2% of the specimens and reached a sensitivity of 86.5%. CISH positivity always matched with HPV-DNA positivity, while 100% of cases with punctated signal joined with cervical intraepithelial neoplasia grade 2 or worse (CIN2+. p16/Ki67 immunohistochemistry gave an interpretable result in 100% of the cases. The use of dual stain significantly increased the agreement between pathologists, which reached 100%. Concordance between dual stain and E6/E7 mRNA test was 89%. In our series, both CISH and p16INK4a/Ki67 dual stain demonstrated high grade of performances. In particular, CISH would help to distinguish episomal from integrated HPV, in order to allow conclusions regarding the prognosis of the lesion, while p16INK4a/Ki67 dual stain approach would confer a high level of standardization to the diagnostic procedure.

  14. Chromogenic in situ hybridization and p16/Ki67 dual staining on formalin-fixed paraffin-embedded cervical specimens: correlation with HPV-DNA test, E6/E7 mRNA test, and potential clinical applications.

    Science.gov (United States)

    Zappacosta, Roberta; Colasante, Antonella; Viola, Patrizia; D'Antuono, Tommaso; Lattanzio, Giuseppe; Capanna, Serena; Gatta, Daniela Maria Pia; Rosini, Sandra

    2013-01-01

    Although HPV-DNA test and E6/E7 mRNA analyses remain the current standard for the confirmation of human papillomavirus (HPV) infections in cytological specimens, no universally adopted techniques exist for the detection of HPV in formalin-fixed paraffin-embedded samples. Particularly, in routine laboratories, molecular assays are still time-consuming and would require a high level of expertise. In this study, we investigated the possible use of a novel HPV tyramide-based chromogenic in situ hybridization (CISH) technology to locate HPV on tissue specimens. Then, we evaluate the potential usefulness of p16(INK4a)/Ki-67 double stain on histological samples, to identify cervical cells expressing HPV E6/E7 oncogenes. In our series, CISH showed a clear signal in 95.2% of the specimens and reached a sensitivity of 86.5%. CISH positivity always matched with HPV-DNA positivity, while 100% of cases with punctated signal joined with cervical intraepithelial neoplasia grade 2 or worse (CIN2+). p16/Ki67 immunohistochemistry gave an interpretable result in 100% of the cases. The use of dual stain significantly increased the agreement between pathologists, which reached 100%. Concordance between dual stain and E6/E7 mRNA test was 89%. In our series, both CISH and p16(INK4a)/Ki67 dual stain demonstrated high grade of performances. In particular, CISH would help to distinguish episomal from integrated HPV, in order to allow conclusions regarding the prognosis of the lesion, while p16(INK4a)/Ki67 dual stain approach would confer a high level of standardization to the diagnostic procedure.

  15. Oral and genital HPV genotypic concordance between sexual partners.

    Science.gov (United States)

    Beder Ribeiro, Camila Maria; Ferrer, Iracema; Santos de Farias, Andreza Barkokebas; Fonseca, Débora Diniz; Morais Silva, Igor Henrique; Monteiro Gueiros, Luiz Alcino; Carvalho, Alessandra Tavares; Porter, Stephen Ross; Leao, Jair Carneiro

    2014-01-01

    The aim of this study was to verify human papillomavirus (HPV) transmission and genotype concordance among heterosexual couples. Thirty-one married couples were evaluated. All male subjects presented with clinically diagnosed HPV-related malignant or potentially malignant lesions and underwent peniscopy and penile swab. Their female counterparts underwent swabs of the uterine cervix and oral mucosa. HPV-DNA detection was performed by polymerase chain reaction and restriction fragment length polymorphism. HPV-DNA was detected in the penis, vagina/cervix, and oral cavity of 16 couples (51.61%). Of these, HPV-DNA concordance was observed in 14 couples (87.5%). HPV-DNA was amplified in penile and oral sites of 14 couples. Of these, 13 couples reported fellatio (92.85%), most of them (10 couples, 76.9%) without condom use. HPV-DNA concordance was observed in 7/10 of these couples (70%). The three couples (100%) who reported use of condom during fellatio were HPV-DNA discordant (p = 0.025). Lifetime number of female sexual partners and detection of HPV-DNA in the penile mucosa are surrogate markers of exposure to HPV during marriage. Consistent use of condoms may reduce the risk of HPV transmission. Oral acquisition of HPV from oro-genital contact is influenced by lack of condom use and previous sexual behavior of the male partner. In addition, oral transmission of the virus due to fellatio is as common as genital transmission.

  16. Comparison of hybrid capture 2 High-Risk HPV results in the low positive range with cobas® HPV Test results from the ATHENA study.

    Science.gov (United States)

    Rao, Arundhati; Sandri, Maria Teresa; Sideri, Mario; Young, Stephen; Sharma, Abha; Behrens, Catherine

    2013-09-01

    The increasing importance of high-risk human papillomavirus (hrHPV) testing in cervical cancer screening warrants evaluation of HPV DNA tests with an equivocal zone requiring retesting of samples in the low positive range. To compare the results of the digene hc2 High Risk HPV DNA Test (hc2), which has a manufacturer's recommended retesting zone with the cobas HPV Test, a real-time polymerase chain reaction amplification test without an equivocal range. A retrospective subanalysis of the ATHENA study comparing results for hc2 High Risk HPV DNA Test and the cobas HPV Test using the LINEAR ARRAY HPV Genotyping Test (LA) and Sanger sequencing as comparators was performed. The ability of each test to detect high-grade cervical disease in the equivocal range was also evaluated. 5.2% of samples fell within the equivocal zone (RLU/CO 1.0-2.5) and required retesting with the hc2 High Risk HPV DNA Test. In this low-positive range the cobas HPV Test showed better positive percent agreement (PPA) than hc2 High Risk HPV DNA Test for LA and sequencing (84.2% vs.70.9% and 92.1% vs.82.5%, respectively). hc2 High Risk HPV DNA Test and the cobas HPV Test demonstrated comparable sensitivity for detection of high-grade disease in the equivocal range. In the low cobas HPV Test range (cycle threshold [Ct] 40-35), the cobas HPV test again demonstrated a better PPA than hc2 High Risk HPV DNA Test with LA and sequencing as comparators and more high-grade disease was detected by the cobas HPV Test than hc2 High Risk HPV DNA Test. The cobas HPV Test demonstrates reliable performance in the hc2 High Risk HPV DNA Test equivocal zone, thus supporting it as an option for HPV testing that avoids the need for retesting. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. DNA Repair Proteins as Molecular Targets for Cancer Therapeutics

    OpenAIRE

    Kelley, M.R.; Fishel, M.L.

    2008-01-01

    Cancer therapeutics include an ever-increasing array of tools at the disposal of clinicians in their treatment of this disease. However, cancer is a tough opponent in this battle and current treatments which typically include radiotherapy, chemotherapy and surgery are not often enough to rid the patient of his or her cancer. Cancer cells can become resistant to the treatments directed at them and overcoming this drug resistance is an important research focus. Additionally, increasing discussi...

  18. High HPV Infection Prevalence in Men from Infertile Couples and Lack of Relationship between Seminal HPV Infection and Sperm Quality

    OpenAIRE

    Barbara Golob; Mario Poljak; Ivan Verdenik; Mojca Kolbezen Simoniti; Eda Vrtačnik Bokal; Branko Zorn

    2014-01-01

    Human papillomaviruses (HPV) are the most frequently sexually transmitted viruses and etiological agents of several human cancers. Controversial results of the role of HPV in infertile population on sperm parameters have been published. The aim of this study was to estimate the type-specific prevalence of HPV DNA infection of the external genitalia and semen in 340 Slovenian men from infertile couples and to establish the relationship between seminal HPV DNA infection and abnormal sperm param...

  19. HR-HPV E6/E7 mRNA In Situ Hybridization: Validation Against PCR, DNA In Situ Hybridization, and p16 Immunohistochemistry in 102 Samples of Cervical, Vulvar, Anal, and Head and Neck Neoplasia.

    Science.gov (United States)

    Mills, Anne M; Dirks, Dawn C; Poulter, Melinda D; Mills, Stacey E; Stoler, Mark H

    2017-05-01

    Dysregulated expression of oncogenic types of E6 and E7 is necessary for human papillomavirus (HPV)-driven carcinogenesis. An HPV E6/E7 mRNA in situ hybridization (ISH) assay covering 18 common high-risk types ("HR-RISH," aka HR-HPV RNA18 ISH) has not been extensively studied in the anogenital tract or validated on automated technology. We herein compare HR-RISH to DNA polymerase chain reaction (PCR), p16 immunohistochemistry, and a previously available HPV DNA ISH assay in HPV-related anogenital and head and neck (H&N) neoplasia. A total of 102 squamous intraepithelial lesions (16 CIN1, 25 CIN3, 3 AIN1, 12 AIN3, 9 VIN3)/invasive squamous cell carcinomas (17 cervical, 2 anal, 18 H&N) as well as 10 normal and 15 reactive cervix samples were collected. HR-RISH, DNA ISH, and p16 immunohistochemistry were performed on whole formalin-fixed, paraffin-embedded sections. RNA ISH for 6 low-risk HPV types (LR-RISH) was also performed. RNA and DNA ISH assays used automated systems. HR-HPV PCR was performed on morphology-directed formalin-fixed, paraffin-embedded punches. HR-RISH was ≥97% sensitive for PCR+ and p16+ neoplasia, as well as morphologically defined anogenital high grade squamous intraepithelial lesion/invasive squamous cell carcinoma. HR-RISH was also positive in 78% of anogenital low grade squamous intraepithelial lesion, including 81% of CIN1. Furthermore, a subset of PCR-negative/invalid and p16-negative lesions was positive for HR-RISH. Only 1 problematic reactive cervix sample and no normal cervix samples stained. These results demonstrate that HR-RISH is a robust method for the detection of HR-HPV-related neoplasia and provides insight into HPV pathobiology. Performance meets or exceeds that of existing assays in anogenital and H&N lesions and may play a role in resolving diagnostically challenging CIN1 versus reactive cases.

  20. Human Papillomavirus (HPV) Vaccine

    Science.gov (United States)

    Why get vaccinated?HPV vaccine prevents infection with human papillomavirus (HPV) types that are associated with cause ... at http://www.cdc.gov/hpv. HPV Vaccine (Human Papillomavirus) Information Statement. U.S. Department of Health and ...

  1. HPV Test

    Science.gov (United States)

    ... May 4). Revised Cervical Cancer Screening Guidelines Require Reeducation of Women and Physicians. ACOG [On-line news ... PressAnnouncements/ucm187003.htm. Issued October 16, 2009. Accessd March 23, 2009. National Cancer Institute. Fact Sheet. HPV ...

  2. Prognostic evaluation of DNA index in HIV-HPV co-infected women cervical samples attending in reference centers for HIV-AIDS in Recife.

    Directory of Open Access Journals (Sweden)

    Albert Eduardo Silva Martins

    Full Text Available INTRODUCTION: Persistence of cervical infection caused by human papillomavirus (HPV types with high oncogenic risk may lead to cervical intraepithelial neoplasia (CIN. The aim of the present study was to evaluate whether, in HIV-positive women, the presence of aneuploidy in cervical cell samples is associated with presence and evolution of CIN. METHODS: The present study had two stages. In the first stage, comprising a cross-sectional study, the association between the presence of aneuploidy seen via flow cytometry and sociodemographic characteristics, habits and characteristics relating to HPV and HIV infection was analyzed. In the second stage, comprising a cohort study, it was investigated whether aneuploidy was predictive of CIN evolution. RESULTS: No association was observed between the presence of aneuploidy and HPV infection, or between its presence and alterations seen in oncotic cytological analysis. On the other hand, aneuploidy was associated with the presence of CIN (p = 0.030 in histological analysis and with nonuse of antiretroviral therapy (p = 0.001. Most of the HIV-positive women (234/272 presented normal CD4+ T lymphocyte counts (greater than 350 cells/mm3 and showed a greater aneuploidy regression rate (77.5% than a progression rate (23.9% over a follow-up of up to two years. CONCLUSION: Although there was an association between the presence of cervical tissue lesions and the DNA index, the latter was not predictive of progression of the cervical lesion. This suggests that progression of the cervical lesion to cancer in HIV-positive women may also be changed through improvement of the immunological state enabled by using antiretroviral therapy.

  3. One-prime multi-boost strategy immunization with recombinant DNA, adenovirus, and MVA vector vaccines expressing HPV16 L1 induces potent, sustained, and specific immune response in mice.

    Science.gov (United States)

    Li, Li-Li; Wang, He-Rong; Zhou, Zhi-Yi; Luo, Jing; Xiao, Xiang-Qian; Wang, Xiao-Li; Li, Jin-Tao; Zhou, Yu-Bai; Zeng, Yi

    2016-04-01

    Human papillomavirus (HPV) is associated with various human diseases, including cancer, and developing vaccines is a cost-efficient strategy to prevent HPV-related disease. The major capsid protein L1, which an increasing number of studies have confirmed is typically expressed early in infection, is a promising antigen for such a vaccine, although the E6 and E7 proteins have been characterized more extensively. Thus, the L1 gene from HPV16 was inserted into a recombinant vector, AdHu5, and MVA viral vectors, and administered by prime-boost immunization. Virus-like particles were used as control antigens. Our results indicate that prime-boost immunization with heterologous vaccines induced robust and sustained cellular and humoral response specific to HPV16 L1. In particular, sera obtained from mice immunized with DNA + DNA + Ad + MVA had excellent antitumor activity in vivo. However, the data also confirm that virus-like particles can only elicit low levels cellular immunity and not be long-lasting, and are therefore unsuitable for treatment of existing HPV infections. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. DNA replication and cancer: From dysfunctional replication origin activities to therapeutic opportunities.

    Science.gov (United States)

    Boyer, Anne-Sophie; Walter, David; Sørensen, Claus Storgaard

    2016-06-01

    A dividing cell has to duplicate its DNA precisely once during the cell cycle to preserve genome integrity avoiding the accumulation of genetic aberrations that promote diseases such as cancer. A large number of endogenous impacts can challenge DNA replication and cells harbor a battery of pathways to promote genome integrity during DNA replication. This includes suppressing new replication origin firing, stabilization of replicating forks, and the safe restart of forks to prevent any loss of genetic information. Here, we describe mechanisms by which oncogenes can interfere with DNA replication thereby causing DNA replication stress and genome instability. Further, we describe cellular and systemic responses to these insults with a focus on DNA replication restart pathways. Finally, we discuss the therapeutic potential of exploiting intrinsic replicative stress in cancer cells for targeted therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Cancer immunotherapy using a DNA vaccine encoding a single-chain trimer of MHC class I linked to an HPV-16 E6 immunodominant CTL epitope.

    Science.gov (United States)

    Huang, C-H; Peng, S; He, L; Tsai, Y-C; Boyd, D A K; Hansen, T H; Wu, T-C; Hung, C-F

    2005-08-01

    The potency of DNA vaccines may be affected by the efficiency of intracellular processing and MHC class I presentation of encoded antigens. Since a single-chain trimer (SCT) composed of peptide, beta2-microglobulin (beta2m), and MHC class I heavy chain has been shown to bypass antigen processing and lead to stable presentation of peptides, we investigated the efficacy of a DNA vaccine encoding a SCT composed of an immunodominant CTL epitope of human papillomavirus type 16 (HPV-16) E6 antigen, beta2m, and H-2Kb MHC class I heavy chain (pIRES-E6-beta2m-Kb). Transfection of 293 cells with pIRES-E6-beta2m-Kb can bypass antigen processing and lead to stable presentation of E6 peptide. Furthermore, C57BL/6 mice vaccinated with pIRES-E6-beta2m-Kb exhibited significantly increased E6 peptide-specific CD8+ T-cell immune responses compared to mice vaccinated with DNA encoding wild-type E6. Most importantly, 100% of mice vaccinated with pIRES-E6-beta2m-Kb DNA were protected against a lethal challenge of E6-expressing TC-1 tumor cells. In contrast, all mice vaccinated with wild-type E6 DNA or control plasmid DNA grew tumors. Our data indicate that a DNA vaccine encoding a SCT can lead to stable enhanced MHC class I presentation of encoded antigenic peptide and may be useful for improving DNA vaccine potency to control tumors or infectious diseases.

  6. Study comparing human papillomavirus (HPV) real-time multiplex PCR and Hybrid Capture II INNO-LiPA v2 HPV genotyping PCR assays

    DEFF Research Database (Denmark)

    Iftner, Thomas; Germ, Liesje; Swoyer, Ryan

    2009-01-01

    Human papillomavirus (HPV) DNA genotyping is an essential test to establish efficacy in HPV vaccine clinical trials and HPV prevalence in natural history studies. A number of HPV DNA genotyping methods have been cited in the literature, but the comparability of the outcomes from the different...... methods has not been well characterized. Clinically, cytology is used to establish possible HPV infection. We evaluated the sensitivity and specificity of HPV multiplex PCR assays compared to those of the testing scheme of the Hybrid Capture II (HCII) assay followed by an HPV PCR/line hybridization assay...

  7. Therapeutic Vaccine Strategies against Human Papillomavirus

    Directory of Open Access Journals (Sweden)

    Hadeel Khallouf

    2014-06-01

    Full Text Available High-risk types of human papillomavirus (HPV cause over 500,000 cervical, anogenital and oropharyngeal cancer cases per year. The transforming potential of HPVs is mediated by viral oncoproteins. These are essential for the induction and maintenance of the malignant phenotype. Thus, HPV-mediated malignancies pose the unique opportunity in cancer vaccination to target immunologically foreign epitopes. Therapeutic HPV vaccination is therefore an ideal scenario for proof-of-concept studies of cancer immunotherapy. This is reflected by the fact that a multitude of approaches has been utilized in therapeutic HPV vaccination design: protein and peptide vaccination, DNA vaccination, nanoparticle- and cell-based vaccines, and live viral and bacterial vectors. This review provides a comprehensive overview of completed and ongoing clinical trials in therapeutic HPV vaccination (summarized in tables, and also highlights selected promising preclinical studies. Special emphasis is given to adjuvant science and the potential impact of novel developments in vaccinology research, such as combination therapies to overcome tumor immune suppression, the use of novel materials and mouse models, as well as systems vaccinology and immunogenetics approaches.

  8. Therapeutic Vaccine Strategies against Human Papillomavirus

    Science.gov (United States)

    Khallouf, Hadeel; Grabowska, Agnieszka K.; Riemer, Angelika B.

    2014-01-01

    High-risk types of human papillomavirus (HPV) cause over 500,000 cervical, anogenital and oropharyngeal cancer cases per year. The transforming potential of HPVs is mediated by viral oncoproteins. These are essential for the induction and maintenance of the malignant phenotype. Thus, HPV-mediated malignancies pose the unique opportunity in cancer vaccination to target immunologically foreign epitopes. Therapeutic HPV vaccination is therefore an ideal scenario for proof-of-concept studies of cancer immunotherapy. This is reflected by the fact that a multitude of approaches has been utilized in therapeutic HPV vaccination design: protein and peptide vaccination, DNA vaccination, nanoparticle- and cell-based vaccines, and live viral and bacterial vectors. This review provides a comprehensive overview of completed and ongoing clinical trials in therapeutic HPV vaccination (summarized in tables), and also highlights selected promising preclinical studies. Special emphasis is given to adjuvant science and the potential impact of novel developments in vaccinology research, such as combination therapies to overcome tumor immune suppression, the use of novel materials and mouse models, as well as systems vaccinology and immunogenetics approaches. PMID:26344626

  9. [Evaluation of variable methods for HPV testing].

    Science.gov (United States)

    Cheng, Jiao-ying; Bian, Mei-lu; Ma, Li; Cong, Xiao; Chen, Ying; Liu, Jun

    2013-08-01

    To evaluate clinical efficacy of different HPV methods in screening of cervical cancers. Between August 2011 and November 2011, 424 women in the China-Japan Friendship Hospital were enrolled in this study. All participants were undergone liquid-based cytology test (LCT), Hybrid capture II (HC-II) and real-time (RT) PCR high risk HPV DNA test for HPV16 and HPV18 genotyping. Those results were classified into two group: 424 women at HC-II group with LCT and HC-II test and 421 women at PCR group with LCT and PCR test. All women with atypical squamous cell of undetermined significance (ASCUS) or above in cytological result with high risk HPV positive at two group underwent cervical biopsy by colposcopy.In the mean time, women with negative in cytological results and with HPV 16 and(or) HPV 18 positive also underwent histo-pathological examination by and colposcopy. The results in two groups were discussed:LCT+HC-II group (424 patients) and LCT+PCR12+2 group (421 patients). (1) There was no significant difference in cervical intraepithelial neoplasia (CIN) II or above disease between LCT+HC-II group and LCT+PCR12+2 group (χ(2) = 3.35, P > 0.05).Sensitivity, specificity, positive predictive value and negative predictive value for detection of CINII or above using HC-II and PCR12+2 were 77.8%, 79.4%, 20.4%, 98.1% and 96.3%, 78.2%, 23.2%, 99.7%, respectively. (2) In LCT+PCR12+2 group, it was found 34 women with HPV16 positive, 5 women with HPV 18 positive including 1 women combined with HPV 16 positive, 74 women with other high risk HPV positive and 309 women with HPV negative. Compared to the infection of other high-risk HPV types, HPV 16 and HPV 18 infection leads to a higher chance of cervical lesions with CIN II or above [51.3% (20/39) and 8.1% (6/74) ]. (3) A significant difference of causing cervical cancer and CINII or above was found among women who were infected with HPV 16 and/or HPV 18 infection, with other high-risk HPV types and negative in high-risk HPV

  10. Human papilloma viruses (HPV and breast cancer.

    Directory of Open Access Journals (Sweden)

    James Sutherland Lawson

    2015-12-01

    Full Text Available Purpose: Human papillomaviruses (HPV may have a role in some breast cancers. The purpose of this study is to fill important gaps in the evidence. These gaps are: (i confirmation of the presence of high risk for cancer HPVs in breast cancers, (ii evidence of HPV infections in benign breast tissues prior to the development of HPV positive breast cancer in the same patients, (iii evidence that HPVs are biologically active and not harmless passengers in breast cancer.Methods: RNA-seq data from The Cancer Genome Atlas (TCGA was used to identify HPV RNA sequences in breast cancers. We also conducted a retrospective cohort study based on polymerase chain reaction (PCR analyses to identify HPVs in archival specimens from Australian women with benign breast biopsies who later developed breast cancer. To assess whether HPVs in breast cancer were biologically active, the expression of the oncogenic protein HPV E7 was assessed by immunohistochemistry (IHC.Results: Thirty (3.5% low risk and 20 (2.3% high risk HPV types were identified in 855 breast cancers from the TCGA data base. The high risk types were HPV 18 (48%, HPV 113 (24%, HPV 16 (10%, HPV 52 (10%. Data from the PCR cohort study, indicated that HPV type 18 was the most common type identified in breast cancer specimens (55% of 40 breast cancer specimens followed by HPV 16 (13%. The same HPV type was identified in both the benign and subsequent breast cancer in 15 patients. HPV E7 proteins were identified in 72% of benign breast specimens and 59% of invasive breast cancer specimens.Conclusions: There were 4 observations of particular interest: (i confirmation by both NGS and PCR of the presence of high risk HPV gene sequences in breast cancers, (ii a correlation between high risk HPV in benign breast specimens and subsequent HPV positive breast cancer in the same patient, (iii HPVs in breast cancer are likely to be biologically active (as shown by transcription of HPV DNA to RNA plus the expression of

  11. Continuing rise in oropharyngeal cancer in a high HPV prevalence area: A Danish population-based study from 2011 to 2014

    DEFF Research Database (Denmark)

    Carlander, Amanda-Louise Fenger; Larsen, Christian Grønhøj; Jensen, David Hebbelstrup

    2017-01-01

    and HPV+ BSCCs, although numbers of HPV-negative (HPV–) OPSCC also increased during the study period. The majority of HPV+ tumours were HPV16 DNA positive (86%), but we also identified HPV33 DNA (6%), HPV35 DNA (4%) and others (3%), including HPV18, 26, 31, 45, 56, 58, 59 and HPV67. Conclusion...... An increasing incidence of OPSCC is driven primarily by HPV+ OPSCC. Sixty-two percent of tumours were HPV+, which is a high-prevalence, although the lower number of HPV– cases has yet to stabilise. HPV16 was the predominant genotype, although a significant proportion (14%) was of another genotype. Our......Background Human papillomavirus (HPV) is a critical element in the rising incidence of oropharyngeal squamous cell carcinoma (OPSCC), although whether this trend will continue, and the types of HPV responsible, are currently unknown. We previously demonstrated an increased incidence of HPV...

  12. Novel inhibitor of DNA ligase IV with a promising cancer therapeutic ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Biosciences; Volume 39; Issue 3. Novel inhibitor of DNA ligase IV with a promising cancer therapeutic potential. Ashwin Kotnis Rita Mulherkar. Clipboards Volume 39 Issue 3 June 2014 pp 339-340. Fulltext. Click here to view fulltext PDF. Permanent link:

  13. Quantification of human papilloma virus (HPV) DNA using the Cobas 4800 system in women with and without pathological alterations attributable to the virus.

    Science.gov (United States)

    Álvarez-Argüelles, Marta Elena; de Oña-Navarro, María; Rojo-Alba, Susana; Torrens-Muns, Magdalena; Junquera-Llaneza, Maria Luisa; Antonio-Boga, Jose; Pérez-Castro, Sonia; Melón-García, Santiago

    2015-09-15

    Surrogate markers such as viral load are necessary to follow the evolution of disease resulting from infection with Human Papilloma virus (HPV), especially in this era of vaccination. As such, this paper uses the automated system Cobas-4800-HPV to define viral load as number of HPV copies/cell and apply the results to clinical samples. A curve to determine viral load per cell was constructed from HPV plasmid and cell concentrations using the Cobas-4800-HPV system. According to these curves, HPV viral load was determined in 309 positive endocervical swabs (58 from patients with previous HPV-infection, 118 with current lesions and 133 symptom-free patients presenting for screening) from women attending gynaecology consultations from January to June 2013. In curves with r(2)≥0.95 the Cobas-4800-HPV system has a detection limit of 150 (2.18 log) viral copies, and the limit for β-globin corresponds to that of a single cell. In women reporting for screening, viral load was under 10(4) (4 log) copies/10(3) cells. For women with lesions or previous HPV infection loads were significantly higher particularly in the 30-45 year group (p=0.038). Elevated viral loads were especially noticeable in non-HPV 16/HPV 18. Automated system Cobas-4800-HPV is suitable for define viral load of HPV. Correlation between viral load and number of cells established. Higher viral load in women with disease, and those between 30 and 45 years. Increased viral load of non-16/18 high-risk HPV genotypes detected in patients with lesions compared to screening patients. A difference not observed for HPV 16/18, or in coinfections. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Papanicolau smear chances to be diagnostic for cervical squamous intraepithelial lesions (SIL) with or without detectable HPV DNA at in situ hybridization analysis.

    Science.gov (United States)

    Sopracordevole, F; Cadorin, L; Muffato, G; De Benetti, L; Parin, A

    1993-01-01

    The Authors have correlated 39 cervical diagnostic biopsies for squamous intraepithelial lesions (SILs) with correspective Papanicolau smears (PS), with relation to the presence or the absence of HPV of oncogenic type (HPV-one) detected by in situ hybridization (ISH). Agreement between cytological and histological diagnosis was present in 14 of 16 cases with detectable HPV-one and only in 12 of 23 cases without detectable HPV-one at ISH. The importance of the HPV type in the SILs with relation to the diagnostic accuracy of Papanicolaou smears has been discussed.

  15. An upward trend in DNA p16ink4a methylation pattern and high risk HPV infection according to the severity of the cervical lesion.

    Science.gov (United States)

    Carestiato, Fernanda Nahoum; Afonso, Larissa Alves; Moysés, Natalia; Almeida Filho, Gutemberg Leão; Velarde, Luis Guillermo Coca; Cavalcanti, Silvia Maria Baeta

    2013-01-01

    High-risk human papillomavirus (hr-HPV) infection is necessary but not sufficient for cervical cancer development. Recently, P16INK4A gene silencing through hypermethylation has been proposed as an important cofactor in cervical carcinogenesis due to its tumor suppressor function. We aimed to investigate P16INK4A methylation status in normal and neoplastic epithelia and evaluate an association with HPV infection and genotype. This cross-sectional study was performed with 141 cervical samples from patients attending Hospital Moncorvo Filho, Rio de Janeiro. HPV detection and genotyping were performed through PCR and P16INK4A methylation by nested-methylation specific PCR (MSP). HPV frequency was 62.4% (88/141). The most common HPV were HPV16 (37%), HPV18 (16.3%) and HPV33/45(15.2%). An upward trend was observed concerning P16INK4A methylation and lesion degree: normal epithelia (10.7%), low grade lesions (22.9%), high grade (57.1%) and carcinoma (93.1%) (p HPV infection and genotyping. A correlation was found concerning methylation with HPV infection (p HPV (p = 0.01), HSIL (p cervical carcinoma, we suggest that P16INK4A methylation profile maybe thoroughly investigated as a biomarker to identify patients at risk of cancer.

  16. The prevalence of "high-risk" HPV types in penile condyloma-like lesions: correlation between HPV type and morphology.

    OpenAIRE

    Löwhagen, G B; Bolmstedt, A; Ryd, W; Voog, E

    1993-01-01

    OBJECTIVE--To evaluate the prevalence of "high-risk" human papilloma virus (HPV) types in penile condyloma-like lesions and to correlate HPV types with clinical and histological features. DESIGN--The study included 94 male patients with signs of penile HPV infection. From acuminate, papular and macular lesions, specimens were collected for HPV DNA hybridisation, using the dot blot and Southern blot techniques. Biopsy specimens from 51 cases were examined by light microscopy for signs of koilo...

  17. Comparison of the Abbott RealTime High Risk HPV test and the Roche cobas 4800 HPV test using urine samples.

    Science.gov (United States)

    Lim, Myong Cheol; Lee, Do-Hoon; Hwang, Sang-Hyun; Hwang, Na Rae; Lee, Bomyee; Shin, Hye Young; Jun, Jae Kwan; Yoo, Chong Woo; Lee, Dong Ock; Seo, Sang-Soo; Park, Sang-Yoon; Joo, Jungnam

    2017-05-01

    Human papillomavirus (HPV) testing based on cervical samples is important for use in cervical cancer screening. However, cervical sampling is invasive. Therefore, non-invasive methods for detecting HPV, such as urine samples, are needed. For HPV detection in urine samples, two real-time PCR (RQ-PCR) tests, Roche cobas 4800 test (Roche_HPV; Roche Molecular Diagnostics) and Abbott RealTime High Risk HPV test (Abbott_HPV; Abbott Laboratories) were compared to standard cervical samples. The performance of Roche_HPV and Abbott_HPV for HPV detection was evaluated at the National Cancer Center using 100 paired cervical and urine samples. The tests were also compared using urine samples stored at various temperatures and for a range of durations. The overall agreement between the Roche_HPV and Abbott_HPV tests using urine samples for any hrHPV type was substantial (86.0% with a kappa value of 0.7173), and that for HPV 16/18 was nearly perfect (99.0% with a kappa value of 0.9668). The relative sensitivities (based on cervical samples) for HPV 16/18 detection using Roche_HPV and Abbott_HPV with urine samples were 79.2% (95% CI; 57.9-92.9%) and 81.8% (95% CI; 59.7-94.8%), respectively. When the cut-off CT value for Abbott_HPV was extended to 40 for urine samples, the relative sensitivity of Abbott_HPV increased to 91.7% from 81.8% for HPV16/18 detection and to 87.0% from 68.5% for other hrHPV detection. The specificity was not affected by the change in the CT threshold. Roche_HPV and Abbott_HPV showed high concordance. However, HPV DNA detection using urine samples was inferior to HPV DNA detection using cervical samples. Interestingly, when the cut-off CT value was set to 40, Abbott_HPV using urine samples showed high sensitivity and specificity, comparable to those obtained using cervical samples. Fully automated DNA extraction and detection systems, such as Roche_HPV and Abbott_HPV, could reduce the variability in HPV detection and accelerate the standardization of HPV

  18. High prevalence of HPV among female students in Finland.

    Science.gov (United States)

    Auvinen, Eeva; Niemi, Marja; Malm, Christian; Zilliacus, Robert; Trontti, Anu; Fingerroos, Rita; Lehtinen, Matti; Paavonen, Bjorma

    2005-01-01

    We studied the prevalence of HPV DNA among university students within the Helsinki metropolitan area in Finland. First-y students attending a general health examination as well as students visiting a general practitioner for contraception were enrolled. Vaginal self-samples or cervicovaginal swabs were collected from a total of 1469 students. HPV DNA was determined using a liquid hybridization test. Of all students 33.0% were positive for HPV DNA. Of all positive samples 84.3% were positive for high-risk HPV. The study demonstrated a strikingly high HPV DNA prevalence among the young women. Self-collected samples proved to be acceptable for HPV DNA detection using liquid hybridization.

  19. Seroconversion following anal and genital HPV infection in men: The HIM study

    Directory of Open Access Journals (Sweden)

    Anna R. Giuliano

    2015-12-01

    Full Text Available Background: Protection from naturally acquired human papillomavirus (HPV antibodies may influence HPV infection across the lifespan. This study describes seroconversion rates following genital, anal, and oral HPV 6/11/16/18 infections in men and examines differences by HPV type and anatomic site. Methods: Men with HPV 6/11/16/18 infections who were seronegative for those genotypes at the time of DNA detection were selected from the HPV Infection in Men (HIM Study. Sera specimens collected ≤36 months after detection were analyzed for HPV 6/11/16/18 antibodies using a virus-like particle-based ELISA. Time to seroconversion was separately assessed for each anatomic site, stratified by HPV type. Results: Seroconversion to ≥1 HPV type (6/11/16/18 in this sub-cohort (N=384 varied by anatomic site, with 6.3%, 18.9%, and 0.0% seroconverting following anal, genital, and oral HPV infection, respectively. Regardless of anatomic site, seroconversion was highest for HPV 6 (19.3%. Overall, seroconversion was highest following anal HPV 6 infection (69.2%. HPV persistence was the only factor found to influence seroconversion. Conclusions: Low seroconversion rates following HPV infection leave men susceptible to recurrent infections that can progress to HPV-related cancers. This emphasizes the need for HPV vaccination in men to ensure immune protection against new HPV infections and subsequent disease. Keywords: HPV, Men, Seroconversion, HPV antibodies, Human papillomavirus

  20. Genetic diversity of HPV16 and HPV18 in Brazilian patients with invasive cervical cancer.

    Science.gov (United States)

    Vidal, Joao Paulo C B; Felix, Shayany Pinto; Chaves, Cláudia B P; Patury, Patrícia; Franco, Vanessa F; de Morais, Evaneide A; de Carvalho, Neile A; Carvalho, Aurenice C L; Almeida Neto, Olimpio F; Vieira, Lina Maria T M; Correa, Flavia Miranda; Martins, Luís Felipe Leite; Negrão, Antonio; de Almeida, Liz Maria; Moreira, Miguel Angelo Martins

    2016-07-01

    Cervical cancer is the fourth most common cancer among women, and ∼70-80% of these cancers are associated with two human papillomavirus types: HPV16 and HPV18. Several studies have reported that intra-type diversity is associated with the progression of infection to invasive cancer. Herein, we report the genetic diversity of HPV16 and HPV18 in a cohort of 594 Brazilian women with invasive cervical cancer and describe the prevalence of lineages and intra-type diversity prior to the implementation of the public immunization program in Brazil. HPV detection and genotyping were performed using PCR, PGMY/GP primers, and DNA extracted from fresh tumors. The HPV16 (378 women) and HPV18 (80 women) lineages were identified by PCR and sequencing of the LCR and E6 fragments, followed by SNV comparison and phylogenetic analysis. In our cohort, was found a higher frequency of the lineage A (in 217 women), followed by lineage D (in 97 women) and lineages B and C (in 10 women each) for HPV16; and a higher frequency of lineage A (in 56 women) followed by lineage B (in 15 women) in HPV18. The genetic diversity of HPV16 indicated a recent expansion of specific variants or a selective advantage that is associated with invasive cancer; this pattern was not observed for HPV18. © 2016 Wiley Periodicals, Inc.

  1. HPV and p53 in cervical cancer.

    OpenAIRE

    Ngan, H Y; Stanley, M; Liu, S S; Ma, H K

    1994-01-01

    Objective - To determine the prevalence of HPV 16 and 18 E6 by DNA detection and p53 abnormal protein expression in cervical cancers in Hong Kong. Materials and methods - Seventy-three squamous cell cervical cancer biopsy were analysed. Detection of HPV DNA was carried out by the polymerase chain reaction and Southern blotting (PCR/SB) technique using primers to the HPV16 and 18 E6 region and consensus primers to the L1 region. Abnormal expression of the p53 protein was detected by immunohist...

  2. Human Papillomavirus (HPV)

    Science.gov (United States)

    ... Listen Español Text Size Email Print Share HPV (Human Papillomavirus) Vaccine: What You Need to Know (VIS) ... Why get vaccinated? HPV vaccine prevents infection with human papillomavirus (HPV) types that are associated with many ...

  3. Optimization of Intracellular Transportation of Gene Therapeutic DNA in Small Cell Lung Cancer (Ph.d.)

    DEFF Research Database (Denmark)

    Cramer, Frederik

    2013-01-01

    Small cell lung cancer (SCLC) is a highly malignant disease characterized as being very aggressive and metastasizing at a rapid pace. The malevolent pace of SCLC cell migration results in almost three out of four SCLC patients having disseminated SCLC at the time of diagnosis. Unfortunately...... has to be able to repeated systemic delivery of gene therapy to cancer cells in a both safe and efficient way. Non-viral delivery vectors fulfill many of these requirements except the latter. It is currently very difficult to systemically transport sufficient amounts of therapeutic DNA, by a non...... and thereby improving the efficacy of the treatment. By implementing what is known as a DNA nuclear targeting sequence (DTS) strategy, we found that we could utilize the SCLC cells own transportation system thereby manipulating the cancer cells to bring our therapeutic plasmids from the cytoplasm...

  4. Human papillomavirus (HPV) genotypes associated with laryngeal papilloma.

    Science.gov (United States)

    Corbitt, G; Zarod, A P; Arrand, J R; Longson, M; Farrington, W T

    1988-01-01

    Biopsy specimens from 14 patients treated for laryngeal papillomatosis were tested for the presence of human papillomavirus (HPV) genome by the technique of DNA-DNA hybridisation. According to the age of initial presentation, cases were subdivided into juvenile (less than 16 years) and adult onset (older than 16 years) groups. Histological investigation confirmed that it was impossible to distinguish the groups on this basis. Molecular virology using both dot blot and Southern transfer techniques showed that 10 cases carried the HPV type 6 genome, three cases HPV type 11, and in one case no HPV DNA was detected. All six adult onset cases carried HPV 6 sequences while the juvenile onset group comprised four HPV 6 and three HPV 11 cases. In the juvenile onset group more females were affected; in the adult onset group more males were affected. Two of the patients shown to have HPV type 11 sequences in their biopsy material were the most resistant to treatment. One of the adult onset cases subsequently developed a squamous cell carcinoma of the larynx in which HPV 6 DNA was detected. As far as we know this is first time that HPV-DNA has been confirmed in laryngeal papilloma undergoing malignant change. Images Figs 1 a, b Fig 2 PMID:2834419

  5. Loss of Cell Differentiation in HPV-Associated Bladder Cancer.

    Science.gov (United States)

    Golovina, D A; Ermilova, V D; Zavalishina, L E; Andreeva, Yu Yu; Matveev, V B; Frank, G A; Volgareva, G M

    2016-05-01

    Medical histories of 101 urothelial bladder cancer patients were compared with the results of morphological analysis and biomolecular detection of human papilloma viruses (HPV) in the tumor specimens. DNA of HPV16 (the major type of virus responsible for appearance of cervical carcinoma) was detected in 38 specimens, while mRNA of E6 and E7 oncogenes and E7 oncoprotein of HPV16 were observed in 13 specimens. HPV-positive bladder cancer was characterized by higher degree of cell anaplasia than HPV-negative cancer; in the primary bladder tumor, HPV was detected more often than in recurrent bladder cancer. These data attest to involvement of HPV16 in the genesis of bladder cancer. No correlations of HPV status of bladder tumor with patient's sex, age, and invasion into the muscle layer were revealed.

  6. Male and Couple Fertility Impairment due to HPV-DNA Sperm Infection: Update on Molecular Mechanism and Clinical Impact—Systematic Review

    OpenAIRE

    Salvatore Gizzo; Bruno Ferrari; Marco Noventa; Emanuele Ferrari; Tito Silvio Patrelli; Michele Gangemi; Giovanni Battista Nardelli

    2014-01-01

    Recent evidences identify Human Papillomavirus (HPV) sperm infection as a possible cause of male and couple infertility. It acts through different mechanisms at various steps of human conception and early gestational development. We performed a systematic review to assess the role of HPV semen infection on male and couple infertility. Analysis of available and eligible data does not permit us to fund clear evidences about clinical impact of HPV infection on fertility, although sperm parameter...

  7. Human papilloma virus (HPV) genotypes prevalence in a region of South Italy (Apulia).

    Science.gov (United States)

    Coscia, Maria Franca; Monno, Rosa; Ballini, Andrea; Mirgaldi, Rosanna; Dipalma, Gianna; Pettini, Francesco; Cristallo, Vincenzo; Inchingolo, Francesco; Foti, Caterina; de Vito, Danila

    2015-01-01

    Since human papillomavirus (HPV) is the central casual factor in cervical cancer, understanding the epidemiology and geographical area distribution of the most prevalent HPV genotypes constitutes an important step towards development of strategies of prevention. The aim of this study was to investigate the prevalence of HPV infection and to determine HPV types distribution among 822 HPV positive women and some sexual male partners in Apulia (Italy). HPV DNA detection and genotyping was performed by nested-PCR for the L1 region and reverse line blot hybridization allowing the specific detection of 24 HPV genotyping both high risk (HR) and low risk (LR). The most prevalent HPV genotypes were HPV 16 (35%), HPV 31 (16%) HPV 6 (9%), HPV 58 and 66 (7%), followed by HPV 33 (6%), HPV 18 and 56 (4%), HPV 70 and 45 (3%), HPV 53 and 11 (2%). Currently 1.5% of tested specimens remained unclassified. Multiple infections with at last two different high- risk HPV genotypes were observed in 10% of specimens. This finding adds knowledge to HPV epidemiological investigation, and addresses further studies aimed to consider public health for identifying groups at risk for cervical cancer.

  8. Human papilloma virus (HPV genotypes prevalence in a region of South Italy (Apulia

    Directory of Open Access Journals (Sweden)

    Maria Franca Coscia

    2015-09-01

    Full Text Available INTRODUCTION. Since human papillomavirus (HPV is the central casual factor in cervical cancer, understanding the epidemiology and geographical area distribution of the most prevalent HPV genotypes constitutes an important step towards development of strategies of prevention. AIM. The aim of this study was to investigate the prevalence of HPV infection and to determine HPV types distribution among 822 HPV positive women and some sexual male partners in Apulia (Italy. METHODS. HPV DNA detection and genotyping was performed by nested-PCR for the L1 region and reverse line blot hybridization allowing the specific detection of 24 HPV genotyping both high risk (HR and low risk (LR. RESULTS. The most prevalent HPV genotypes were HPV 16 (35%, HPV 31 (16% HPV 6 (9%, HPV 58 and 66 (7%, followed by HPV 33 (6%, HPV 18 and 56 (4%, HPV 70 and 45 (3%, HPV 53 and 11 (2%. Currently 1.5% of tested specimens remained unclassified. Multiple infections with at last two different high-risk HPV genotypes were observed in 10% of specimens. CONCLUSIONS. This finding adds knowledge to HPV epidemiological investigation, and addresses further studies aimed to consider public health for identifying groups at risk for cervical cancer.

  9. HPV16 E6 seropositivity among cancer-free men with oral, anal or genital HPV16 infection

    Science.gov (United States)

    Beachler, Daniel C.; Waterboer, Tim; Campbell, Christine M. Pierce; Ingles, Donna J.; Kuhs, Krystle A. Lang; Nyitray, Alan G.; Hildesheim, Allan; Pawlita, Michael; Kreimer, Aimée R.; Giuliano, Anna R.

    2016-01-01

    Antibodies against the Human papillomavirus 16 (HPV16) E6 oncoprotein appear years prior to clinical diagnosis of anal and oropharyngeal cancer, but whether they develop around the time of HPV infection is unclear. Serum samples from 173 cancer-free men from the Human Papillomavirus Infection in Men (HIM) Study were tested for HPV antibodies and DNA. HPV16 E6 seropositivity was low among men with oral HPV16-infection (1/28; 3.6%, 95%CI=0.0%-18.4%), anal HPV16-infection (1/61; 1.6%, 95%CI=0.0%-8.8%), and 24-month persistent genital HPV16-infection (1/84; 1.2%, 0.0-6.5%). This suggests E6 seroconversion may not occur around the time of oral, anal, or genital HPV16 acquisition. PMID:28239675

  10. HPV16 E6 seropositivity among cancer-free men with oral, anal or genital HPV16 infection.

    Science.gov (United States)

    Beachler, Daniel C; Waterboer, Tim; Pierce Campbell, Christine M; Ingles, Donna J; Kuhs, Krystle A Lang; Nyitray, Alan G; Hildesheim, Allan; Pawlita, Michael; Kreimer, Aimée R; Giuliano, Anna R

    2016-12-01

    Antibodies against the Human papillomavirus 16 (HPV16) E6 oncoprotein appear years prior to clinical diagnosis of anal and oropharyngeal cancer, but whether they develop around the time of HPV infection is unclear. Serum samples from 173 cancer-free men from the Human Papillomavirus Infection in Men (HIM) Study were tested for HPV antibodies and DNA. HPV16 E6 seropositivity was low among men with oral HPV16-infection (1/28; 3.6%, 95%CI=0.0%-18.4%), anal HPV16-infection (1/61; 1.6%, 95%CI=0.0%-8.8%), and 24-month persistent genital HPV16-infection (1/84; 1.2%, 0.0-6.5%). This suggests E6 seroconversion may not occur around the time of oral, anal, or genital HPV16 acquisition.

  11. Immunogenicity and therapeutic effects of a Mycobacterium tuberculosis rv2190c DNA vaccine in mice.

    Science.gov (United States)

    Liang, Yan; Zhang, Xiaoyan; Bai, Xuejuan; Xiao, Li; Wang, Xiaomei; Zhang, Junxian; Yang, Yourong; Song, Jinying; Wang, Lan; Wu, Xueqiong

    2017-02-27

    Tuberculosis (TB) is a major global public health problem. New treatment methods on TB are urgently demanded. In this study, Mycobacterium tuberculosis (MTB) rv2190c DNA vaccine was prepared and its immunogenicity and therapeutic effects were evaluated. Non-infected mice immunized with rv2190c DNA or ag85a DNA showed higher levels of interferon-gamma (IFN-γ) in stimulated spleen lymphocyte culture supernatants, and had more Th1 cells and an elevatory ratio of Th1/Th2 immune cells in whole blood, indicating that Th1-type immune response was predominant. Compared with the saline group, ag85a DNA group and rv2190c DNA group in the infected mice decreased the lung colony-forming units (CFUs) by 0.533 and 0.283 log10, and spleen CFUs by 0.425 and 0.321 log10 respectively, and pathological lesion. The rv2190c DNA had some immunotherapeutic effect on TB.

  12. HPV infection among women in a representative rural and suburban population of the USA.

    Science.gov (United States)

    Lee, Sin Hang; Vigliotti, Veronica S; Pappu, Suri

    2009-06-01

    To study the prevalence of low-risk and high-risk HPV genotypes in a largely suburban, non-Hispanic, white female population of the USA, and to determine the positive predictive value of one-occasion HPV detection and genotyping using high-grade squamous intraepithelial lesion (HSIL) cytology as the endpoint for clinical evaluation. HPV DNA present in liquid-based cytology specimens collected by gynecologists in private practice was amplified using nested polymerase chain reaction. HPV DNA was validated by signature DNA sequencing for accurate genotyping. Of 2633 specimens, 278 were positive for HPV DNA of any genotype. Among 255 single HPV infections, the most prevalent genotype was HPV-16 (n=50; 19.6%), followed by HPV-52 (n=24; 9.4%). Only 10 specimens, all positive for a high-risk HPV, were associated with an HSIL cytology result. Among them were 6 of the 50 specimens (12%) tested positive for HPV-16. One novel HPV-39 variant was detected in repeat testing in a patient with persistent HPV infection. DNA sequencing is a useful method for increasing the specificity of HPV genotyping as an aid to follow persistent high-risk HPV infections to reduce excessive colposcopies in populations with low cancer prevalence.

  13. Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine

    Science.gov (United States)

    Baron, Mira; Levin, Myron J; Chatterjee, Archana; Fox, Bradley; Scholar, Sofia; Rosen, Jeffrey; Chakhtoura, Nahida; Meric, Dorothée; Dessy, Francis J; Datta, Sanjoy K; Descamps, Dominique; Dubin, Gary

    2011-01-01

    In this observer-blind study (NCT00423046), women (N = 1,106), stratified by age (18–26, 27–35, 36–45 y), were randomized (1:1) to receive the HPV-16/18 vaccine (Cervarix®, GlaxoSmithKline Biologicals, Months 0, 1, 6) or the HPV-6/11/16/18 vaccine (Gardasil® Merck and Co., Inc., Months 0, 2, 6). Month 7 results were previously reported; we now report Month 24 results. In the according-to-protocol cohort for immunogenicity (seronegative and DNA-negative at baseline for HPV type analyzed), seropositivity rates of neutralizing antibodies (nAbs) [pseudovirion-based neutralization assay] were, across all age strata, 100% (HPV-16/18 vaccine) and 97.5–100% (HPV-6/11/16/18 vaccine) for HPV-16, and 99.0–100% (HPV-16/18 vaccine) and 72.3–84.4% (HPV-6/11/16/18 vaccine) for HPV-18. Corresponding geometric mean titers (GMTs) were 2.4–5.8-fold higher for HPV-16 and 7.7–9.4-fold higher for HPV-18 with the HPV-16/18 vaccine vs. the HPV-6/11/16/18 vaccine; HPV-16 and HPV-18 GMTs were significantly higher with the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (p vaccinated cohort (received ≥1 vaccine dose, irrespective of baseline sero/DNA-status). Similar results were obtained using enzyme-linked immunosorbent assay (ELISA ). Positivity rates and GMTs of antigen-specific IgG antibodies in cervicovaginal secretions (ELISA) were not significantly different between vaccines. At Month 24, CD4+ T-cell responses for HPV-16 and HPV-18 were higher with the HPV-16/18 vaccine; memory B-cell response was higher for HPV-18 with the HPV-16/18 vaccine and similar between vaccines for HPV-16. Both vaccines were generally well tolerated. Although an immunological correlate of protection has not been defined, differences in the magnitude of immune response between vaccines may represent determinants of duration of protection. PMID:22048173

  14. Perceptions and Experiences of Human Papillomavirus (HPV) Infection and Testing among Low-Income Mexican Women

    OpenAIRE

    Le?n-Maldonado, Leith; Wentzell, Emily; Brown, Brandon; Allen-Leigh, Betania; Torres-Ibarra, Leticia; Salmer?n, Jorge; Billings, Deborah L.; Thrasher, James F.; Lazcano-Ponce, Eduardo

    2016-01-01

    Background HPV infection causes cervical cancer, a major contributor to morbidity and mortality among low-income Mexican women. Human papillomavirus (HPV) DNA testing is now a primary screening strategy in Mexico?s early cervical cancer detection program (ECDP). Research on Mexican women?s perceptions of HPV and testing is necessary for establishing culturally appropriate protocols and educational materials. Here, we explore perceptions about HPV and HPV-related risk factors among low-income ...

  15. Human Papillomavirus (HPV) Prevalence in Male Adolescents 4 Years After HPV-16/18 Vaccination.

    Science.gov (United States)

    Lehtinen, Tuomas; Söderlund-Strand, Anna; Petäjä, Tiina; Eriksson, Tiina; Jokiranta, Sakari; Natunen, Kari; Dillner, Joakim; Lehtinen, Matti

    2017-11-15

    We assessed human papillomavirus (HPV) prevalence among HPV-16/18-vaccinated and unvaccinated Finnish male adolescents participating in chlamydia screening 4 years after vaccination with AS04-adjuvanted HPV-16/18 vaccine in 2007-2009. Previously vaccinated (n = 395) or unvaccinated (n = 149) male adolescents were enrolled in 12 municipalities. First-void urine samples were tested for HPV types 6, 11, 16, 18, 31, 33, 35, 45, 51, 52, 56, 58, 59, 66, and 68, and prevalence rates for HPV-16/18, and HPV-11/16/18/31/33/45 were reduced profoundly (0% vs 2.1% [P = .02] and 0.8% vs 5.3 [P = .002], respectively). Overall HPV DNA prevalence was also significantly reduced among HPV-16/18-vaccinated (4.1%) compared with unvaccinated subjects (10.1%) (P = .01). In this post hoc study, a highly significant reduction in HPV prevalence 4 years after vaccination suggests that the bivalent HPV-16/18 vaccine has protective efficacy in men. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  16. Factors associated with HPV-DNA clearance in a cohort of HIV-positive patients: role of cART and gender

    Directory of Open Access Journals (Sweden)

    Elisa Suardi

    2014-11-01

    Full Text Available Introduction: We aimed to assess any factors associated with dysplasia regression and with HPV clearance in a cohort of HIV+ patients, with particular focus on cART and gender. Methods: Asymptomatic HIV+ patients of the San Paolo Infectious Disease (SPID cohort who underwent anoscopy/gynaecological evaluation were enrolled. Anal/cervical brushing were analyzed for: HPV-PCR detection/genotyping (HR-HPV, cytologic abnormalities (Bethesda System 2001: LSIL-HSIL. Demographics and HIV-related parameters were evaluated at baseline. Activated CD8+/CD38+ lymphocytes were measured (flow citometry. Patients were examined at baseline (T0 and at 12–18 months visit (T1. HPV clearance was defined as negativisation of HPV at T1; SIL regression (SIL-R and progression (SIL-P were defined as change from HSIL/LSIL to a lower-grade/absence of dysplasia and as change from absence of HSIL/LSIL to a higher-grade dysplasia at T1, respectively. Mann Whitney test, Chi-square test and multivariate logistic regression were used. Results: A total of 189 patients were examined, 60 (32% were women. One hundred fifty patients (79% were HPV+, 113 (75% harboured HR-HPV; 103 (68% showed LSIL/HSIL at T0 (32% of women and 65% of men (all were HPV-positive. No differences in demographics and HIV-related markers were found between patients with SIL-P (33, 41% and patients with SIL-R (47, 59%. HPV+ patients who cleared HPV (28, 18% were found to be more frequently female, heterosexual infected, more frequently on cART and with lower Log10 HIV-RNA and lower levels of CD8+/CD38+ % compared with HPV persistence group (Table 1.No differences in PI exposure were found between the two groups (p=.08. Interestingly, also when only HR-HPV were considered, clearance was associated with exposure to cART (naïve 4%, vs cART 86%, p=.048. In multivariate analysis, heterosexuals (AOR 5.123, 95% CI 1.5–17.5 vs homosexuals were independently associated to HPV clearance, whereas CD8+/CD38+% (AOR 0

  17. AN UPWARD TREND IN DNA P16INK4A METHYLATION PATTERN AND HIGH RISK HPV INFECTION ACCORDING TO THE SEVERITY OF THE CERVICAL LESION

    Directory of Open Access Journals (Sweden)

    Fernanda Nahoum Carestiato

    2013-09-01

    Full Text Available SUMMARY High-risk human papillomavirus (hr-HPV infection is necessary but not sufficient for cervical cancer development. Recently, P16INK4A gene silencing through hypermethylation has been proposed as an important cofactor in cervical carcinogenesis due to its tumor suppressor function. We aimed to investigate P16INK4A methylation status in normal and neoplastic epithelia and evaluate an association with HPV infection and genotype. This cross-sectional study was performed with 141 cervical samples from patients attending Hospital Moncorvo Filho, Rio de Janeiro. HPV detection and genotyping were performed through PCR and P16INK4A methylation by nested-methylation specific PCR (MSP. HPV frequency was 62.4% (88/141. The most common HPV were HPV16 (37%, HPV18 (16.3% and HPV33/45(15.2%. An upward trend was observed concerning P16INK4A methylation and lesion degree: normal epithelia (10.7%, low grade lesions (22.9%, high grade (57.1% and carcinoma (93.1% (p < 0.0001. A multivariate analysis was performed to evaluate an association between methylation, age, tobacco exposure, HPV infection and genotyping. A correlation was found concerning methylation with HPV infection (p < 0.0001, hr-HPV (p = 0.01, HSIL (p < 0.0007 and malignant lesions (p < 0.0001. Since viral infection and epigenetic alterations are related to cervical carcinoma, we suggest that P16INK4A methylation profile maybe thoroughly investigated as a biomarker to identify patients at risk of cancer.

  18. Comparison of the diagnostic value of cervical cytology and HPV HR DNA testing for the diagnosis of low-grade and high-grade squamous intraepithelial lesions across different age groups.

    Science.gov (United States)

    Paluszkiewicz, Aleksandra; Pruski, Dominik; Iwaniec, Kinga; Kędzia, Witold

    2017-01-01

    To assess the diagnostic value of cervical cytology and HPV HR DNA testing for the diagnosis of low grade and high-grade squamous intraepithelial lesions across different age groups. The study included 1103 patients, age 25-70 years. All patients underwent in-depth diagnostic tests following either an abnormal Pap test result or a clinically suspicious cervical lesion. In all women the following examinations were performed: a molecular test detecting 14 high-risk types of HPV, a colposcopy examination, as well as directed-biopsy of the cervix. The studied population was subdivided into four age groups. It was observed that the percentage of high grade squamous intraepithelial lesions (HSIL) and cancers increased with women's age. Sensitivity of both methods for detecting high-grade squamous intraepithelial lesions was highest for women aged 40-49 years. Sensitivity values of HPV testing was higher than that of cervical cytology among women under age 50. Specificity of HPV testing increased significantly with age of women and was several fold higher across all age groups than the specificity of cervical cytology.

  19. Identification of multiple HPV types on spermatozoa from human sperm donors

    DEFF Research Database (Denmark)

    Kaspersen, Maja D; Larsen, Peter B; Ingerslev, Hans Jakob

    2011-01-01

    Human papillomaviruses (HPV) may cause sexually transmitted disease. High-risk types of HPV are involved in the development of cervical cell dysplasia, whereas low-risk types may cause genital condyloma. Despite the association between HPV and cancer, donor sperm need not be tested for HPV...... according to European regulations. Consequently, the potential health risk of HPV transmission by donor bank sperm has not been elucidated, nor is it known how HPV is associated with sperm. The presence of 35 types of HPV was examined on DNA from semen samples of 188 Danish sperm donors using a sensitive...

  20. HIV/AIDS, HPV and Anal Cancer

    Science.gov (United States)

    Wang, Chia-ching J.; Sparano, Joseph; Palefsky, Joel M.

    2016-01-01

    SYNOPSIS Anal cancer is an increasingly common non-AIDS-defining cancer among HIV-infected individuals. It is associated with human papillomavirus (HPV), the most common sexually transmitted infectious agent. The 14 oncogenic types of HPV are causally associated with 5–10% of all cancers, notably anogenital cancers. HPV16 is the most common genotype detected in about 70% of anal cancers. The HPV types detected in anal cancer are included in the 9-valent vaccine. HPV vaccines have demonstrated efficacy in reducing anal precancerous lesions in HIV-infected individuals. The standard treatment for anal cancer has been fluorouracil (5-FU) and mitomycin (or cisplatin) as chemotherapy agents plus radiation, which can also be effectively used for the HIV-infected patients. Continued studies will be needed to test new treatment strategies in HIV-infected patients with anal cancer to determine which treatment protocols provide the best therapeutic index. PMID:27889034

  1. Analysis of E2 gene integrity in HPV16 and HPV58 viruses isolated from women with cervical pathology

    OpenAIRE

    González-Losa,María del R; Puerto-Solis,Marylin; Tenorio Ruiz,Juan; Rosado-López,Ariel I; Hau-Aviles,Oscar; Ayora-Talavera,Guadalupe; Cisneros-Cutz,Isidro; Conde-Ferráez,Laura

    2016-01-01

    Integration of human papillomavirus (HPV) DNA into human cells accompanied by the disruption of the viral genome has been described as a prerequisite for cancer development. This study aimed to investigate E2 gene integrity of HPV16 and HPV58 viruses isolated from infected women with cervical lesions. Forty-two HPV16- and 31 HPV58-positive samples were analysed. E2 integrity was assumed when all fragments covering the E2 gene were amplified with specific polymerase chain reaction primers. Ove...

  2. Loss of CHD1 causes DNA repair defects and enhances prostate cancer therapeutic responsiveness

    DEFF Research Database (Denmark)

    Kari, Vijayalakshmi; Mansour, Wael Yassin; Raul, Sanjay Kumar

    2016-01-01

    The CHD1 gene, encoding the chromo-domain helicase DNA-binding protein-1, is one of the most frequently deleted genes in prostate cancer. Here, we examined the role of CHD1 in DNA double-strand break (DSB) repair in prostate cancer cells. We show that CHD1 is required for the recruitment of Ct......IP to chromatin and subsequent end resection during DNA DSB repair. Our data support a role for CHD1 in opening the chromatin around the DSB to facilitate the recruitment of homologous recombination (HR) proteins. Consequently, depletion of CHD1 specifically affects HR-mediated DNA repair but not non......-homologous end joining. Together, we provide evidence for a previously unknown role of CHD1 in DNA DSB repair via HR and show that CHD1 depletion sensitizes cells to PARP inhibitors, which has potential therapeutic relevance. Our findings suggest that CHD1 deletion, like BRCA1/2 mutation in ovarian cancer, may...

  3. Human papillomavirus 16 (HPV16 enhances tumor growth and cancer stemness of HPV-negative oral/oropharyngeal squamous cell carcinoma cells via miR-181 regulation

    Directory of Open Access Journals (Sweden)

    Sung Hee Lee

    2015-12-01

    Full Text Available High-risk human papillomaviruses (e. g., HPV16, HPV18 are closely associated with the development of head and neck cancers including oral/oropharyngeal squamous cell carcinoma (OSCC. We previously demonstrated immortalization of normal human oral keratinocytes by introducing high-risk HPV whole genome, suggesting that HPV infection plays an important role in the early stage of oral carcinogenesis. Although HPV infection may occur in different stages of cancer development, roles of HPV in exacerbating malignant phenotypes in already-transformed cells in the context of cancer stemness are not clearly defined. In this study, we investigated the role of HPV16 in promoting the virulence of HPV-negative OSCC. Introducing HPV16 whole genome in HPV-negative OSCC increased malignant growth and self-renewal capacity, a key characteristic of cancer stem cells (CSCs. HPV16 also enhanced other CSC properties, including aldehyde dehydrogenase 1 (ALDH1 activity, migration/invasion, and CSC-related factor expression. Mechanistically, we found that HPV16 inhibited the expression of miR-181a and miR-181d (miR-181a/d at the transcriptional level. Ectopic expression of miR-181a/d decreased anchorage independent growth and CSC phenotype of HPV16-transfected OSCC. Furthermore, silencing of miR-181a/d target genes, i. e., K-ras and ALDH1, abrogated the effects of HPV16 in HPV16-transfected OSCC, supporting the functional importance of HPV16/miR-181a/d axis in HPV-mediated oral carcinogenesis. Our study suggests that high-risk HPV infection further promotes malignancy in HPV-negative OSCC by enhancing cancer stemness via miR-181a/d regulation. Consequently, miR-181a/d may represent a novel therapeutic agent for the treatment of HPV-positive OSCC. Keywords: HPV, OSCC, cancer stem cells, miR-181

  4. Seroconversion Following Anal and Genital HPV Infection in Men: The HIM Study

    Science.gov (United States)

    Giuliano, Anna R.; Viscidi, Raphael; Torres, B. Nelson; Ingles, Donna J.; Sudenga, Staci L.; Villa, Luisa L.; Baggio, Maria Luiza; Abrahamsen, Martha; Quiterio, Manuel; Salmeron, Jorge; Lazcano-Ponce, Eduardo

    2015-01-01

    Background Protection from naturally acquired human papillomavirus (HPV) antibodies may influence HPV infection across the lifespan. This study describes seroconversion rates following genital, anal, and oral HPV 6/11/16/18 infections in men and examines differences by HPV type and anatomic site. Methods Men with HPV 6/11/16/18 infections who were seronegative for those genotypes at the time of DNA detection were selected from the HPV Infection in Men (HIM) Study. Sera specimens collected ≤36 months after detection were analyzed for HPV 6/11/16/18 antibodies using a virus-like particle-based ELISA. Time to seroconversion was separately assessed for each anatomic site, stratified by HPV type. Results Seroconversion to ≥1 HPV type (6/11/16/18) in this sub-cohort (N=384) varied by anatomic site, with 6.3, 18.9, and 0.0% seroconverting following anal, genital, and oral HPV infection, respectively. Regardless of anatomic site, seroconversion was highest for HPV 6 (19.3%). Overall, seroconversion was highest following anal HPV 6 infection (69.2%). HPV persistence was the only factor found to influence seroconversion. Conclusions Low seroconversion rates following HPV infection leave men susceptible to recurrent infections that can progress to HPV-related cancers. This emphasizes the need for HPV vaccination in men to ensure immune protection against new HPV infections and subsequent disease. PMID:26688833

  5. Prospects for exploring the molecular-genomic foundations of therapeutic hypnosis with DNA microarrays.

    Science.gov (United States)

    Rossi, Ernest Lawrence

    A new perspective on how therapeutic hypnosis and neuroscience may be integrated on the molecular-genomic level is offered as a guide for basic research and clinical applications. An update of Watson and Crick's original formulation of molecular biology is proposed to illustrate how psychosocial experiences modulate gene expression, protein synthesis, and brain plasticity during memory trace reactivation for the reorganization of neural networks that encode fear, stress, and traumatic symptoms. Examples of the scientific literature on DNA microarrays are used to explore how this new technology could integrate therapeutic hypnosis, neuroscience, and psychosocial genomics as a new foundation for mind-body medicine. Researchers and clinicians in therapeutic hypnosis need to partner with colleagues in neuroscience and molecular biology that utilize DNA microarray technology. It is recommended that hypnotic susceptibility scales of the future incorporate gene expression data to include the concept of "embodied imagination" and the "ideo-plastic faculty" on a molecular-genomic level as well as the psychological and behavioral level of ideomotor and ideosensory responses that are currently assessed.

  6. Comparison of the immunogenicity of Cervarix® and Gardasil® human papillomavirus vaccines for oncogenic non-vaccine serotypes HPV-31, HPV-33, and HPV-45 in HIV-infected adults.

    Science.gov (United States)

    Toft, Lars; Tolstrup, Martin; Müller, Martin; Sehr, Peter; Bonde, Jesper; Storgaard, Merete; Østergaard, Lars; Søgaard, Ole S

    2014-01-01

    Individuals infected with human immunodeficiency virus (HIV) have excess risk of developing human papillomavirus (HPV)-related disease. A substantial fraction of HPV-associated cancers is caused by HPV serotypes not included in the currently available vaccines. Among healthy women, both Cervarix(®) (HPV-16/18, GlaxoSmithKline Biologicals, GSK) and Gardasil(®) (HPV-6/11/16/18, Merck) have demonstrated partial cross-protection against certain oncogenic non-vaccine HPV-types. Currently, there are no available data on vaccine-induced cross-protection in men and little is known about cross-reactive immunity after HPV-vaccination of HIV-infected individuals. In an investigator-initiated trial, we randomized 91 HIV-positive men and women to receive vaccination with Cervarix(®) or Gardasil(®). The HPV-DNA status of the participants was determined with pcr before and after immunization. Cross-reactive antibody responses against HPV-31, HPV-33, and HPV-45 were evaluated for up to 12 months using a pseudovirion-based neutralization assay (PBNA). Geometric mean antibody titers (GMTs) were compared among vaccine groups and genders at 7 and 12 months.: Both vaccines induced anti-HPV-31, -33, and -45 neutralizing antibodies in participants who were seronegative and HPV-DNA negative for those types at study entry. Geometric mean antibody titers were comparable between vaccine groups. Interestingly, anti-HPV-31 and -33 antibody titers were higher among women compared with men at 7 and 12 months.: In conclusion, both licensed HPV-vaccines induced cross-neutralizing antibodies against frequent oncogenic non-vaccine serotypes HPV-31, HPV-33, and HPV-45 in HIV-infected adults, and women had greater serological responses against HPV-31 and -33 compared with men.

  7. HPV and Cancer

    Science.gov (United States)

    Human papillomaviruses (HPVs) are a group of more than 200 related viruses that can cause several cancers including cervical cancer, anal cancer, and oropharyngeal cancer. Learn more about how HPV is transmitted, the different types of HPV, HPV vaccines, and HPV treatment.

  8. HPV induced cervical carcinogenesis: molecular basis and vaccine development.

    Science.gov (United States)

    Kaufmann, A M; Backsch, C; Schneider, A; Dürst, M

    2002-11-01

    Association of infection with papillomavirus and dysplasia of the cervix uteri has been firmly established. There are only few cervical cancers where no HPV DNA is detectable. The mechanism of epithelial cell immortalization by interaction with tumour suppressor genes p53 and pRb by viral oncogenes E6 and E7 is elucidated. Progression of the HPV infected cell to a malignant phenotype involves further modification of host gene expression and/or mutations. The appearance of chromosomal aberrations can lead to mutational inactivation or loss of tumour suppressor genes (TSG), activation and amplification of oncogenes, with importance for the process of carcinogenesis. Oncogene amplification, with exception of few reports, seems not to be a major mechanism in cervical carcinogenesis. In contrast, cytogenetic and loss of heterozygosity (LOH) results from CIN and invasive cancer demonstrate alterations at specific chromosomal regions, pointing at localisation of TSG. Genetic alterations at chromosomes 3p, 6p, 1lq were frequently found early in tumour development Primary invasive carcinoma showed additional allelic losses at chromosome arms 6q, 17p and 18q. Useful biological diagnostic and prognostic markers for high-risk HPV infection and malignant progression may be p16NK4 p27Kip, and NET-I/C4.8. Putative senescence genes relevant for HPV-induced carcinogenesis are localized on chromosomes 2, 4 and 10. Genes for Telomerase suppression are presumably located on chromosomes 3, 4 and 6. Natural immune responses to HPV infection exist Therefore, immune therapy is an attractive possibility for prevention and therapy of HPV infection. To date, vaccine development has reached clinical evaluation. Prophylaxis aims at the induction of virus neutralizing antibodies to capsid proteins. Virus-like particle vaccines are currently tested in clinical trials. Due to the long lag period between infection and clinical manifestation trials will take a long time until conclusive results are

  9. Vertical transmission of HPV in pregnancy. A prospective clinical study of HPV-positive pregnant women.

    Science.gov (United States)

    Jach, Robert; Galarowicz, Bartłomiej; Huras, Hubert; Pawlik, Dorota; Basta, Tomasz; Streb, Joanna; Wolski, Hubert; Ludwin, Artur; Ludwin, Inga

    2014-09-01

    Human papillomavirus (HPV) is the most common sexually transmitted infection. Data reporting vertical transmission of HPV from the mother to the fetus are inconsistent and scant. Vertical transmission may occur by hematogenic route (transplacental), or by ascending contamination, or through the birth canal, which may result in the dreaded and rare laryngeal papillomatosis. Infected sperm at fertilization is a potential route of infection, too. The objective of the study was to evaluate the rate of vertical transmission of HPV in HPV-positive pregnant women to their newborn infants, as well as the risk factors of HPV vertical transmission. The clinical material was provided by 136 pregnant women, aged 18-45 years. Out of this group, 30 (22.05%) women with abnormal Pap test and positive DNA HPV test were prospectively observed Neonatal status, i.e. DNA HPV from the nasopharyngeal smear was recorded in all infants during the perinatal period. The conventional Pap test was performed with the cervix brush in all women. The Bethesda 2011 classification system was applied. An average C Reactive Protein (CRP) concentration in the studied pregnant women was 711.6083 (Std Dev--12.93). The most frequent cytological findings in the cervical smears from the examined women were ASCUS, n = 13 (43.3%), then--LSIL, n = 10 (33.3%), HSIL--n = 5 (16.7%) and AGC--n = 2 (6.7%). In the neonates, the presence of LR HPV DNA was detected in 9 cases (30.0%) and HR HPV DNA in 7 cases (23.3%). Fourteen neonates (46.7%) tested HPV DNA negative in the perinatal period. HPV infection (incidental or chronic) is observed in approximately 22% of pregnant women from the Matopolska province. Neonatal HPV infection in HPV-positive women was observed in 53.3% of the subjects. CRP concentration > 10 mg/dl in the serum of pregnant women statistically significantly (p 0.001) reduces the risk of vertical transmission of HPV from the mother to the fetus.

  10. Can human papillomavirus (HPV) genotyping classify non-16/18 high-risk HPV infection by risk stratification?

    Science.gov (United States)

    2016-01-01

    Objective Infection with high-risk genotypes of human papillomavirus (HR-HPV) is the major cause of invasive cervical cancers. HPV-16 and HPV-18 are known to be responsible for two-thirds of all invasive cervical carcinomas, followed by HPV-45, -31, and -33. Current guidelines only differentiate HPV-16/18 (+) by recommending direct colposcopy for treatment. We tried to evaluate whether there are differences in risk among 12 non-16/18 HR-HPV genotypes in this study. Methods The pathology archive database records of 1,102 consecutive gynecologic patients, who had results for cervical cytology and histology and for HPV testing, as determined by HPV 9G DNA chip, were reviewed. Results Among the 1,102 patients, 346 were non-16/18 HR-HPV (+) and 231 were HPV-16/18 (+). We calculated the odds ratios for ≥cervical intraepithelial neoplasia 2 (CIN 2) of 14 groups of each HR-HPV genotype compared with a group of HR-HPV (–) patients. Based on the odds ratio of each genotype, we divided patients with non-16/18 HR-HPV genotypes (+) into two groups: HPV-31/33/35/45/52/58 (+) and HPV-39/51/56/59/66/68 (+). The age-adjusted odds ratios for ≥CIN 2 of the HPV-31/33/35/45/52/58 (+) and HPV-39/51/56/59/66/68 (+) groups compared with a HR-HPV (–) group were 11.9 (95% CI, 7.6 to 18.8; pHPV-16/18 (+) group was 18.1 (95% CI, 11.6 to 28.3; p=0.003). Conclusion The 12 non-16/18 HR-HPV genotypes can be further categorized (HPV-31/33/35/45/52/58 vs. HPV-39/51/56/59/66/68) by risk stratification. The HPV-31/33/35/45/52/58 genotypes might need more aggressive action. Large scale clinical trials or cohort studies are necessary to confirm our suggestion. PMID:27550402

  11. Therapeutic touch affects DNA synthesis and mineralization of human osteoblasts in culture.

    Science.gov (United States)

    Jhaveri, Ankur; Walsh, Stephen J; Wang, Yatzen; McCarthy, MaryBeth; Gronowicz, Gloria

    2008-11-01

    Complementary and alternative medicine (CAM) techniques are commonly used in hospitals and private medical facilities; however, the effectiveness of many of these practices has not been thoroughly studied in a scientific manner. Developed by Dr. Dolores Krieger and Dora Kunz, Therapeutic Touch is one of these CAM practices and is a highly disciplined five-step process by which a practitioner can generate energy through their hands to promote healing. There are numerous clinical studies on the effects of TT but few in vitro studies. Our purpose was to determine if Therapeutic Touch had any effect on osteoblast proliferation, differentiation, and mineralization in vitro. TT was performed twice a week for 10 min each on human osteoblasts (HOBs) and on an osteosarcoma-derived cell line, SaOs-2. No significant differences were found in DNA synthesis, assayed by [(3)H]-thymidine incorporation at 1 or 2 weeks for SaOs-2 or 1 week for HOBs. However, after four TT treatments in 2 weeks, TT significantly (p = 0.03) increased HOB DNA synthesis compared to controls. Immunocytochemistry for Proliferating Cell Nuclear Antigen (PCNA) confirmed these data. At 2 weeks in differentiation medium, TT significantly increased mineralization in HOBs (p = 0.016) and decreased mineralization in SaOs-2 (p = 0.0007), compared to controls. Additionally, Northern blot analysis indicated a TT-induced increase in mRNA expression for Type I collagen, bone sialoprotein, and alkaline phosphatase in HOBs and a decrease of these bone markers in SaOs-2 cells. In conclusion, Therapeutic Touch appears to increase human osteoblast DNA synthesis, differentiation and mineralization, and decrease differentiation and mineralization in a human osteosarcoma-derived cell line. (c) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  12. Delineation of the HPV11E6 and HPV18E6 Pathways in Initiating Cellular Transformation

    Directory of Open Access Journals (Sweden)

    Lamech M. Mwapagha

    2017-11-01

    Full Text Available Although high-risk human papillomaviruses (HPVs are the major risk factors for cervical cancer they have been associated with several other cancers, such as head and neck and oral cancers. Since integration of low-risk HPV11 DNA has been demonstrated in esophageal tumor genomes, this study compared the effects of low-risk HPV11E6 and high-risk HPV18E6 on cellular gene expression. The HPV11E6 and HPV18E6 genes were cloned into an adenoviral vector and expressed in human keratinocytes (HaCaT in order to investigate early events and to eliminate possible artifacts introduced by selective survival of fast growing cells in stable transfection experiments. HPV11E6 had very little effect on p21 and p53 gene expression, while HPV18E6 resulted in a marked reduction in both these proteins. Both HPV11E6 and HPV18E6 enabled growth of colonies in soft agar, but the level of colony formation was higher in HPV18E6 infected cells. DNA microarray analysis identified significantly differentially regulated genes involved in the cellular transformation signaling pathways. These findings suggest that HPV11E6 and HPV18E6 are important in initiating cellular transformation via deregulation of signaling pathways such as PI3K/AKT and pathways that are directly involved in DNA damage repair, cell survival, and cell proliferation. This study shows that the low-risk HPV11E6 may have similar effects as the high-risk HPV18E6 during the initial stages of infection, but at a much reduced level.

  13. College women, HPV genotyping and sexual behavior before HPV vaccination: Results from samples stored for a long time.

    Science.gov (United States)

    Herrera-Ortiz, Antonia; Conde-Glez, Carlos Jesús; Olamendi-Portugal, Ma Leonidez; García-Cisneros, Santa; Plett-Torres, Tanya; Sánchez-Alemán, Miguel A

    2017-10-06

    HPV is the sexually transmitted agent most common among young people, like college students. The aim of study was to associate sexual behavior characteristics of women with HPV, detected in genital samples taken before the introduction of the HPV vaccine. Female students during 2001-2005 donated genital samples and the samples were re-analyzed in 2013 for HPV genotyping by RT-PCR. The frozen storage of the students' genital samples allowed the detection of HPV DNA and its genotyping after years of sample collection. HPV prevalence was 22%, HPV16 3.9%, and HPV18 1.1%. Age, multiple sexual partners and the partner's age at first sexual intercourse were significantly associated to HPV. Students with ≥ 3 sexual partners and who did not use condom had 12.8 higher odds of being HPV positive. These results made possible the analysis of HPV prevalence changes, before HPV vaccine introduction. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Human papilloma virus (HPV) molecular diagnostics.

    Science.gov (United States)

    Kroupis, Christos; Vourlidis, Nikolaos

    2011-11-01

    Human Papilloma Virus (HPV) is becoming a menace worldwide, especially to the developing world, due to its involvement in a variety of malignancies, with cervical cancer being the most important and prevalent. There are many HPV types; HPV 16/18 are the most carcinogenic but few others are also characterized as high-risk (HR). They can cause a variety of low- or high-grade cellular abnormalities, most frequently detected in a routine Pap test. Most infections clear within 2 years, however, a minority persists and potentially could progress to cervical cancer. Molecular tests detecting HPV DNA, RNA or proteins are now being available either commercially or in-house developed. DNA detection is nowadays an established tool for diagnosis and monitoring of HPV-related disease, however, there is lack of a reference method and standardization with reference materials. The various available test formats create confusion on which molecular test to choose and what are its limitations. Therefore, the need for lab accreditation and participation in proficiency testing has to be stressed. Novel HPV biomarkers (RNA, protein etc.) are now intensively examined for their inclusion as adjunct tools. Recently, developed prophylactic vaccines for HPV 16/18 have already proven safe and efficient and raise high expectations for the complete eradication of these types in the future.

  15. Human Papillomavirus (HPV) virion induced cancer and subfertility, two sides of the same coin.

    Science.gov (United States)

    Depuydt, C E; Beert, J; Bosmans, E; Salembier, G

    2016-12-01

    In the natural history of HPV infections, the HPV virions can induce two different pathways, namely the infec- tious virion producing pathway and the clonal transforming pathway. An overview is given of the burden that is associated with HPV infections that can both lead to cervical cancer and/or temporal subfertility. That HPV infections cause serious global health burden due to HPV-associated cancers is common knowledge, but that it is also responsible for a substantial part of idiopathic subfertility is greatly underestimated. The bulk of the detected HPV DNA whether in men or women is however infectious from origin. Because the dissociation between HPV viruses and HPV virions or infection and disease remains difficult for clinicians as well as for HPV detection, we propose a review of the different effects caused by the two different HPV virion induced pathways, and highlight the mechanisms that are responsible for causing transient subfertility and cancer.

  16. HPV infection among rural American Indian women and urban white women in South Dakota: an HPV prevalence study

    Directory of Open Access Journals (Sweden)

    Muller Clemma J

    2011-09-01

    Full Text Available Abstract Background High-risk strains of human papillomavirus (HPV cause cervical cancer. American Indian (AI women in the Northern Plains of the U.S. have significantly higher incidence and mortality rates for cervical cancer than White women in the same geographical area. We compared HPV prevalence, patterns of HPV types, and infection with multiple HPV types in AI and White women living in South Dakota, U.S. Methods We analyzed the HPV status of cervical samples collected in 2006-2008 from women aged 18-65 years who attended two rural AI reservation clinics (n = 235 or an urban clinic in the same area serving mostly White women (n = 246. Data collection occurred before HPV vaccination was available to study participants. HPV DNA was amplified by using the L1 consensus primer system and an HPV Linear Array detection assay to identify HPV types. We used chi-square tests to compare HPV variables, with percentages standardized by age and lifetime number of sexual partners. Results Compared to White women, AI women were younger (p = 0.01 and reported more sexual partners (p p p = 0.001. Infections among AI women showed a wider variety and very different pattern of HPV types, including a higher prevalence of mixed HPV infections (19% [95% CI = 26-38] vs. 7% [95% CI = 4-11]; p = 0.001. AI women had a higher percentage of HPV infections that were not preventable by HPV vaccination (32% [95% CI = 26-38] vs. 15% [95% CI = 11-21]; p Conclusions A higher HPV burden and a different HPV genotyping profile may contribute to the high rate of cervical cancer among AI women.

  17. Determination of human papillomavirus type 16 genotype and construction of cloning vector pTZ57R encoding HPV16 E7 gene.

    Science.gov (United States)

    Meshkat, Zahra; Soleimanjahi, Hoorieh; Mahmoudi, Mahmoud; Mirshahabi, Hessam; Hassan, Zuhair M; Ghaffari, Saeed R; Sabokbar, Tayebeh

    2007-10-01

    To isolate and construct a cloning vector containing the human papillomavirus (HPV)16-E7 gene as a target for application as a DNA vaccine. The study was performed in 2005 in Iran. The E7 gene, one of the most important HPV oncoproteins and a target molecule for therapeutic vaccines, was amplified by polymerase chain reaction (PCR). The PCR product was cloned into a suitable cloning vector and confirmed by colony-PCR, restriction enzyme analysis, and sequenced. The desired plasmid was sequenced and indicated 99% homology with those mentioned in the Genbank. The Iranian HPV16 E7 gene sequence is very similar to other sequences in the Genbank, and it can be used as a candidate gene in a therapeutic vaccine for Iranian patients with cervical cancer.

  18. Comparison of clinical performances among Roche Cobas HPV, RFMP HPV PapilloTyper and Hybrid Capture 2 assays for detection of high-risk types of human papillomavirus.

    Science.gov (United States)

    Yu, Shinae; Kwon, Min-Jung; Lee, Eun Hee; Park, Hyosoon; Woo, Hee-Yeon

    2015-09-01

    The cervical cancer screening guidelines suggest that early detection of HPV16 and HPV18 is helpful for identifying women with cervical intraepithelial neoplasia (CIN) grade two or higher. We comparatively evaluated three HPV DNA assays, Roche Cobas HPV, RFMP HPV PapilloTyper, and Hybrid Capture 2 (HC2). A total of 861 cervical swab samples from women over 30 years of age were classified into two groups, that is, high grade squamous intraepithelial lesion (HSIL) and non-HSIL, according to cervical cytology results and analyzed by three assays. The results of direct sequencing or Linear array HPV genotyping test were considered true when the three assays presented discrepancies. The concordance rates between Roche Cobas HPV versus RFMP HPV PapilloTyper, RFMP HPV PapilloTyper versus HC2, and Roche Cobas versus HC2 were 94.5%, 94.3%, and 95.9%, respectively. For detection of HPV16 and HPV18, Roche Cobas HPV showed the concordance rates of 98.3% (κ = 0.73) and 99.4% (κ = 0.40) with the confirmation tests, respectively; and RFMP HPV PapilloTyper showed the concordance rates of 99.5% (κ = 0.92) and 100.0% (κ = 1.00), respectively. In conclusion, Roche Cobas HPV, RFMP HPV PapilloTyper, and HC2 showed high agreement rates. Roche Cobas HPV and RFMP HPV PapilloTyper are particularly useful, since both provide HPV specific genotypes, HPV16 and HPV18. © 2015 Wiley Periodicals, Inc.

  19. Identification of multiple HPV types on spermatozoa from human sperm donors.

    Science.gov (United States)

    Kaspersen, Maja D; Larsen, Peter B; Ingerslev, Hans Jakob; Fedder, Jens; Petersen, Gert Bruun; Bonde, Jesper; Höllsberg, Per

    2011-03-29

    Human papillomaviruses (HPV) may cause sexually transmitted disease. High-risk types of HPV are involved in the development of cervical cell dysplasia, whereas low-risk types may cause genital condyloma. Despite the association between HPV and cancer, donor sperm need not be tested for HPV according to European regulations. Consequently, the potential health risk of HPV transmission by donor bank sperm has not been elucidated, nor is it known how HPV is associated with sperm. The presence of 35 types of HPV was examined on DNA from semen samples of 188 Danish sperm donors using a sensitive HPV array. To examine whether HPV was associated with the sperm, in situ hybridization were performed with HPV-6, HPV-16 and -18, and HPV-31-specific probes. The prevalence of HPV-positive sperm donors was 16.0% and in 66.7% of these individuals high-risk types of HPV were detected. In 5.3% of sperm donors, two or more HPV types were detected. Among all identified HPV types, 61.9% were high-risk types. In situ hybridization experiments identified HPV genomes particularly protruding from the equatorial segment and the tail of the sperm. Semen samples from more than one in seven healthy Danish donors contain HPV, most of them of high-risk types binding to the equatorial segment of the sperm cell. Most HPV-positive sperm showed decreased staining with DAPI, indicative of reduced content of DNA. Our data demonstrate that oncogenic HPV types are frequent in men.

  20. Identification of multiple HPV types on spermatozoa from human sperm donors.

    Directory of Open Access Journals (Sweden)

    Maja D Kaspersen

    Full Text Available Human papillomaviruses (HPV may cause sexually transmitted disease. High-risk types of HPV are involved in the development of cervical cell dysplasia, whereas low-risk types may cause genital condyloma. Despite the association between HPV and cancer, donor sperm need not be tested for HPV according to European regulations. Consequently, the potential health risk of HPV transmission by donor bank sperm has not been elucidated, nor is it known how HPV is associated with sperm. The presence of 35 types of HPV was examined on DNA from semen samples of 188 Danish sperm donors using a sensitive HPV array. To examine whether HPV was associated with the sperm, in situ hybridization were performed with HPV-6, HPV-16 and -18, and HPV-31-specific probes. The prevalence of HPV-positive sperm donors was 16.0% and in 66.7% of these individuals high-risk types of HPV were detected. In 5.3% of sperm donors, two or more HPV types were detected. Among all identified HPV types, 61.9% were high-risk types. In situ hybridization experiments identified HPV genomes particularly protruding from the equatorial segment and the tail of the sperm. Semen samples from more than one in seven healthy Danish donors contain HPV, most of them of high-risk types binding to the equatorial segment of the sperm cell. Most HPV-positive sperm showed decreased staining with DAPI, indicative of reduced content of DNA. Our data demonstrate that oncogenic HPV types are frequent in men.

  1. Comparisons of VLP-Based ELISA, Neutralization Assays with Native HPV, and Neutralization Assays with PsV in Detecting HPV Antibody Responses in HIV-Infected Women.

    Science.gov (United States)

    Du, Ping; Brendle, Sarah; Milici, Janice; Camacho, Fabian; Zurlo, John; Christensen, Neil; Meyers, Craig

    2015-03-01

    Human papillomavirus (HPV)-associated cancers are important public health problems in HIV-infected people. Assays based on HPV virus-like particles (VLP) and pseudoviruses (PsV) are commonly used to examine HPV antibody responses in HIV-infected people, but neutralization assays with native HPV have not been utilized and a comparison of these three assays is lacking. We evaluated the agreement of assays using VLP, native HPV and PsV in detecting HPV16 and 18 antibodies in HIV-infected women. The VLP-based ELISA (VLP-ELISA) was used to detect antibody responses to HPV16 and 18 and cottontail rabbit papillomavirus (CRPV) VLP antigens. Neutralization assays with native HPV (NA-HPV) and with PsV (NA-PsV) were conducted to examine HPV16 or 18 neutralizing antibodies. Intra class correlation coefficients (ICC) and kappa coefficients were used to assess the agreements of seropositivity between the assays. The seroprevalence detected by the VLP-ELISA, NA-HPV and NA-PsV in 94 HIV-infected women was 35%, 51% and 27% for HPV16 and 14%, 44% and 21% for HPV18. Cross-reactivity between HPV16 and HPV18 was 0.35, 0.04 and 0.33 (kappa coefficients) for the VLP-ELISA, NA-HPV and NA-PsV. The agreements of seropositivity between the three assays were low. Six women who were HPV16 DNA positive were seropositive by the NA-HPV but only two were HPV16 seropositive by the VLP-ELISA or NA-PsV. One HPV18 DNA positive woman was seropositive by all three assays. Repeated tests indicated excellent reproducibility of the NA-HPV. HPV serology results vary across different assays. The NA-HPV appears to be a sensitive and reliable approach in detecting natural HPV antibodies in HIV-infected women. The NA-HPV can be applied in both HPV natural history studies and vaccine studies in HIV-infected people.

  2. Identification of the type of human papillomavirus (HPV in patients with cervical cancer

    Directory of Open Access Journals (Sweden)

    Marlina Marlina

    2016-12-01

    Full Text Available Human Papillomavirus (HPV is the most significant risk factor for the cause of cervical cancer. The purpose of this study for identification of HPV types 16, 18, 31, 33, 45 and 52 in cervical cancer patients. HPV is a row of high-risk HPV types that can cause cervical cancer. Total sample of 78 diisolat DNA derived from FFPE, cervical smears and cervical cancer fresh tissue obtained from Dr. Dr. M. Djamil, Padang and hospitals. Arifin Achmad, Pekanbaru. HPV DNA detection is done by using Polymerase Chain Reaction (PCR using universal primers GP5 +/6 +. HPV types were identified by PCR with specific primers. Total sample types obtained with concentrations varying between 0.9 to 645 ng / ml with purity DNA in accordance with the specified purity for PCR amplification. The results of the study of 78 patients with cervical cancer samples, 42 samples (54% identified HPV DNA. HPV type 18 is more dominant and followed by HPV type 16 as compared to the other types, namely the percentage of 40.4% and 28.5%. HPV type 45 (7.1%, HPV type 52 (2.3% and HPV 31 and HPV type 33 was not detected.

  3. Therapeutic role of curcumin in oxidative DNA damage caused by formaldehyde.

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    Ciftci, Gulay; Aksoy, Abdurrahman; Cenesiz, Sena; Sogut, Mehtap Unlu; Yarim, Gul Fatma; Nisbet, Cevat; Guvenc, Dilek; Ertekin, Ali

    2015-05-01

    Formaldehyde is a common environmental contaminant that causes oxidative DNA damage in cells by increasing the production of reactive oxygen species. The aim of this study was to investigate the amount of 8-hydroxy-deoxyguanosine (8-OhdG), tumor protein 53(TP53), beta-amyloid[Aß(1-42), Aß (1-40)], total antioxidant capacity (TAC) and malondialdehyde (MDA) and the therapeutic role of curcumin in rat cells with oxidative DNA damage caused by formaldehyde. The control group was given physiological saline for 15 days (i.p.) and the second group was given 37% formaldehyde (i.p.) at a dose of 9 mg/kg group every other day. The third group was given 9 mg/kg formaldehyde (i.p.) every other day and treated therapeutically with 100 mg/kg curcumin every day by gavage. At the end of the trial period, urine, blood, and brain tissue was collected from the rats. The levels of MDA in sera were increased and the TAC, TP53, and Aß (1-40) levels were reduced in the formaldehyde-treated group with respect to the control group (pformaldehyde-treated group and reduced after treatment with curcumin (P formaldehyde-treated group (P  0.05). In conclusion, the oxidative stress caused by formaldehyde exposure was reduced with the application of curcumin. © 2015 Wiley Periodicals, Inc.

  4. RECQL1 DNA repair helicase: a potential therapeutic target and a proliferative marker against ovarian cancer.

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    Sakiko Sanada

    Full Text Available OBJECTIVE: This study analyzed the clinicopathological correlation between ovarian cancer (OC and RECQL1 DNA helicase to assess its therapeutic potential. METHODS: Surgically resected OC from 118 retrospective cases, for which paraffin blocks and all clinical data were complete, were used in this study. RECQL1 and Ki-67 immunostaining were performed on sections to correlate RECQL1 staining with subtype and patient survival. Ten OC and two normal cell lines were then examined for RECQL1 expression and were treated with siRNA against RECQL1 to assess its effect on cell proliferation. RESULTS: Of the 118 cases of adenocarcinoma (50, serous; 26, endometrioid; 21, clear cell; 15, mucinous; 6, other histology, 104 (90% showed varying levels of RECQL1 expression in the nuclei of OC cells. The Cox hazards model confirmed that diffuse and strong staining of RECQL1 was correlated with histological type. However, RECQL1 expression did not correlate with overall patient survival or FIGO stage. In vitro, RECQL1 expression was exceptionally high in rapidly growing OC cell lines, as compared with normal cells. Using a time-course analysis of RECQL1-siRNA transfection, we observed a significant inhibition in cell proliferation. CONCLUSIONS: RECQL1 DNA helicase is a marker of highly proliferative cells. RECQL1-siRNA may offer a new therapeutic strategy against various subtypes of OC, including platinum-resistant cancers, or in recurrent cancers that gain platinum resistance.

  5. HPV genotype-specific concordance between EuroArray HPV, Anyplex II HPV28 and Linear Array HPV Genotyping test in Australian cervical samples

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    Alyssa M. Cornall

    2017-12-01

    Full Text Available Purpose: To compare human papillomavirus genotype-specific performance of two genotyping assays, Anyplex II HPV28 (Seegene and EuroArray HPV (EuroImmun, with Linear Array HPV (Roche. Methods: DNA extracted from clinican-collected cervical brush specimens in PreservCyt medium (Hologic, from 403 women undergoing management for detected cytological abnormalities, was tested on the three assays. Genotype-specific agreement were assessed by Cohen's kappa statistic and Fisher's z-test of significance between proportions. Results: Agreement between Linear Array and the other 2 assays was substantial to almost perfect (κ = 0.60 − 1.00 for most genotypes, and was almost perfect (κ = 0.81 – 0.98 for almost all high-risk genotypes. Linear Array overall detected most genotypes more frequently, however this was only statistically significant for HPV51 (EuroArray; p = 0.0497, HPV52 (Anyplex II; p = 0.039 and HPV61 (Anyplex II; p=0.047. EuroArray detected signficantly more HPV26 (p = 0.002 and Anyplex II detected more HPV42 (p = 0.035 than Linear Array. Each assay performed differently for HPV68 detection: EuroArray and LA were in moderate to substantial agreement with Anyplex II (κ = 0.46 and 0.62, respectively, but were in poor disagreement with each other (κ = −0.01. Conclusions: EuroArray and Anyplex II had similar sensitivity to Linear Array for most high-risk genotypes, with slightly lower sensitivity for HPV 51 or 52. Keywords: Human papillomavirus, Genotyping, Linear Array, Anyplex II, EuroArray, Cervix

  6. Decision-analytic modeling to evaluate the long-term effectiveness and cost-effectiveness of HPV-DNA testing in primary cervical cancer screening in Germany

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    Krämer, Alexander

    2010-01-01

    Full Text Available Background: Persistent infections with high-risk types of human papillomavirus (HPV are associated with the development of cervical neoplasia. Compared to cytology HPV testing is more sensitive in detecting high-grade cervical cancer precursors, but with lower specificity. HPV based primary screening for cervical cancer is currently discussed in Germany. Decisions should be based on a systematic evaluation of the long-term effectiveness and cost-effectiveness of HPV based primary screening. Research questions: What is the long-term clinical effectiveness (reduction in lifetime risk of cervical cancer and death due to cervical cancer, life years gained of HPV testing and what is the cost-effectiveness in Euro per life year gained (LYG of including HPV testing in primary cervical cancer screening in the German health care context? How can the screening program be improved with respect to test combination, age at start and end of screening and screening interval and which recommendations should be made for the German health care context? Methods: A previously published and validated decision-analytic model for the German health care context was extended and adapted to the natural history of HPV infection and cervical cancer in order to evaluate different screening strategies that differ by screening interval, and tests, including cytology alone, HPV testing alone or in combination with cytology, and HPV testing with cytology triage for HPV-positive women. German clinical, epidemiological and economic data were used. In the absence of individual data, screening adherence was modelled independently from screening history. Test accuracy data were retrieved from international meta-analyses. Predicted outcomes included reduction in lifetime-risk for cervical cancer cases and deaths, life expectancy, lifetime costs, and discounted incremental cost-effectiveness ratios (ICER. The perspective of the third party payer and 3% annual discount rate were

  7. Cause-specific mortality in HPV+ and HPV- oropharyngeal cancer patients

    DEFF Research Database (Denmark)

    Nørregaard, Cecilie; Grønhøj, Christian; Jensen, David

    2017-01-01

    ; 1.00 year), secondary malignancies (n = 131; 2.37 years), cardiovascular and pulmonary causes (n = 58; 3.48 years), and unspecified causes (n = 102; 3.42 years). HPV/p16 status was the strongest predictor of improved survival across all causes of death. The only cause of death to decrease...... in incidence over the 2 years after treatment was death from OPSCC. HPV/p16 positivity was an independent factor for improved survival across all causes of death in patients with OPSCC. In addition, both HPV-positive and HPV-negative OPSCC patients faced high 5- and 10-year mortality rates. Implementing......Identifying the causes of death in head and neck cancer patients can optimize follow-up and therapeutic strategies, but studies in oropharyngeal squamous cell carcinoma (OPSCC) patients stratified by HPV status are lacking. We report cause-specific mortality in a population-based cohort of patients...

  8. Correlation between HPV sperm infection and male infertility

    OpenAIRE

    Yang YANG; Jia, Chan-Wei; Ma, Yan-Min; Zhou, Li-Ying; Wang, Shu-Yu

    2013-01-01

    Human papillomavirus (HPV) is one of the most common sexually transmitted diseases which comprises a group of small DNA viruses that infect both cutaneous and mucous squamous epithelia. Liquid bead microarray technology (LBMA) were used to evaluate 24 HPV genotypes in confirmed fertile and infertile males of North China so that the effects of HPV infection on semen parameters and relationship with male infertility could be discussed. A total of 1138 subjects were recruited in this study; 142 ...

  9. Racial differences in the incidence and clearance of human papilloma virus (HPV): the HPV in men (HIM) study.

    Science.gov (United States)

    Schabath, Matthew B; Villa, Luisa L; Lin, Hui-Yi; Fulp, William J; Akogbe, Gabriel O; Abrahamsen, Martha E; Papenfuss, Mary R; Lazcano-Ponce, Eduardo; Salmerón, Jorge; Quiterio, Manuel; Giuliano, Anna R

    2013-10-01

    This analysis assessed the acquisition (incidence) and persistence (clearance) of human papilloma virus (HPV) infection by self-reported race among men in The HPV in Men (HIM) Study, a multinational prospective study of the natural history of genital HPV infections. Self-reported race was categorized as White, Black, Asian/Pacific Islander (PI), or multiple and mixed race. Genital samples were combined for HPV DNA testing and categorized by any, oncogenic, and non-oncogenic HPV infections. Asian/PI race had significantly the lowest incidence of any, oncogenic, and non-oncogenic HPV infection (P HPV infection (HR = 0.61; 95% CI, 0.40-0.93) when compared to Whites. No significant associations were evident for Asian/PI race for clearance. Multiple and mixed race was significantly associated with lower probability of acquiring non-oncogenic HPV infection (HR = 0.83; 95% CI, 0.69-0.99) and borderline significant associations were observed for any HPV (HR = 0.91) and oncogenic infections (HR = 0.92). Multiple and mixed race was associated with a lower probability of clearing any (HR = 0.92; 95% CI, 0.84-1.00) and oncogenic HPV infections (HR = 0.85; 95% CI, 0.75-0.95). Asian/PI race had the lowest incidence of HPV and exhibited a lower probability of acquiring new HPV infections. Multiple and mixed race had the second lowest incidence of infection and was associated with a lower probability of acquiring and clearing an HPV infection. Race-specific differences in HPV infection could be due to behavior, innate genetic differences, or circulating intratypic HPV variants.

  10. Human papillomavirus (HPV prevalence and types among Turkish women at a gynecology outpatient unit

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    Dursun Polat

    2009-01-01

    Full Text Available Abstract Background Human Papillomavirus (HPV is a well-known pathogen for lower genital tract neoplasias, yet little is known regarding HPV prevalence in Turkey. The aim of this study was to investigate the prevalence of HPV DNA and to determine HPV types distribution among women with normal and abnormal cytology. Methods A total of five hundred seven (n = 507 women were retrospectively evaluated between 2004-2008. Conventional polymerase chain reaction was used to detect the presence of HPV types in cervicovaginal samples obtained from patients during gynecologic examination. Results One hundred four (n = 104 of the women were excluded from the study because of the incomplete data and a total of 403 women were used for the final analysis. There were, 93 (23% women with cytologic abnormality and 310 (77% women with normal cytology. Overall, 23% of the women was HPV positive. The overall prevalence of HPV in women with abnormal Pap smears was 36% (93/403, of which in ASCUS 22%, LSIL 51% and HSIL 60%. Also, HPV DNA was positive in 20% of the women with normal cervical cytology. The most common HPV types in cytologically normal women were as follows; HPV 16 (36%, HPV 6 (22% and HPV 18 (13%. The rate of other HPV types were as follows; HPV11 4.4%, HPV45 4.4%, HPV90 4.4%, HPV35 2.2%, HPV67 2.2%, HPV81 2.2%, and multiple type HPVs 8.9%. The most common HPV types in cytologically abnormal women were HPV 16 (35%, HPV6 (19% and HPV18 (8%. The rate of multiple HPV infections in women with normal Pap test was 2.2%. Conclusion HPV prevalence and type distribution in this study were similar to that reported worldwide at least in our study population. Hovewer, HPV prevalence was more common compared with previous studies reported from Turkey. This might be related with methodology and hospital based patient accrual and high rate of women with abnormal cytology. Further population based prospective studies are needed to eliminate the drawbacks of our study

  11. Analysis of E2 gene integrity in HPV16 and HPV58 viruses isolated from women with cervical pathology

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    María del R González-Losa

    Full Text Available Integration of human papillomavirus (HPV DNA into human cells accompanied by the disruption of the viral genome has been described as a prerequisite for cancer development. This study aimed to investigate E2 gene integrity of HPV16 and HPV58 viruses isolated from infected women with cervical lesions. Forty-two HPV16- and 31 HPV58-positive samples were analysed. E2 integrity was assumed when all fragments covering the E2 gene were amplified with specific polymerase chain reaction primers. Overall, in 59% of the samples, at least one fragment was not amplified in HPV16- (57% and HPV58-positive samples (61%. Samples from high-grade squamous intraepithelial lesions had the highest frequency of E2 gene disruptions (73%, followed by samples from low-grade squamous intraepithelial lesions (63% and, finally, samples from invasive cervical cancer (35%. Association between the integrity status of the E2 gene, and lesion grade was assessed by the chi-squared test applied to the combined set of viruses (p = 0.6555 or to populations of the same virus type (HPV58, p = 0.3101; HPV16, p = 0.3024. In conclusion, in this study, no association was found between the presence of E2 gene disruptions and the grade of cervical lesions caused by HPV16 and HPV58.

  12. Analysis of E2 gene integrity in HPV16 and HPV58 viruses isolated from women with cervical pathology.

    Science.gov (United States)

    González-Losa, María Del R; Puerto-Solis, Marylin; Tenorio Ruiz, Juan; Rosado-López, Ariel I; Hau-Aviles, Oscar; Ayora-Talavera, Guadalupe; Cisneros-Cutz, Isidro; Conde-Ferráez, Laura

    2016-12-01

    Integration of human papillomavirus (HPV) DNA into human cells accompanied by the disruption of the viral genome has been described as a prerequisite for cancer development. This study aimed to investigate E2 gene integrity of HPV16 and HPV58 viruses isolated from infected women with cervical lesions. Forty-two HPV16- and 31 HPV58-positive samples were analysed. E2 integrity was assumed when all fragments covering the E2 gene were amplified with specific polymerase chain reaction primers. Overall, in 59% of the samples, at least one fragment was not amplified in HPV16- (57%) and HPV58-positive samples (61%). Samples from high-grade squamous intraepithelial lesions had the highest frequency of E2 gene disruptions (73%), followed by samples from low-grade squamous intraepithelial lesions (63%) and, finally, samples from invasive cervical cancer (35%). Association between the integrity status of the E2 gene, and lesion grade was assessed by the chi-squared test applied to the combined set of viruses (p = 0.6555) or to populations of the same virus type (HPV58, p = 0.3101; HPV16, p = 0.3024). In conclusion, in this study, no association was found between the presence of E2 gene disruptions and the grade of cervical lesions caused by HPV16 and HPV58.

  13. Are women with lupus at higher risk of HPV infection?

    Science.gov (United States)

    Klumb, E M; Pinto, A C; Jesus, G R; Araujo, M; Jascone, L; Gayer, C R; Ribeiro, F M; Albuquerque, E M N; Macedo, J M B

    2010-11-01

    Human papillomavirus (HPV) is the etiological agent of cervical cancer, the second most prevalent neoplasia among women. Although it has been proven that systemic lupus erythematosus (SLE) patients have higher frequency of cervical dysplasia, few studies have focused on HPV prevalence among them. This study aimed to investigate HPV prevalence among SLE patients and to evaluate associated risk factors, including the use of immunosuppressors (IM). Total DNA extracted from cervical samples of 173 SLE patients and 217 women (control group) submitted to routine cervical cytopathology was used as template in polymerase chain reaction (PCR)-based assays for detection of HPV DNA. HPV genotyping was performed by type-specific PCR, PCR-RFLP and/or DNA sequencing. Statistical methods included univariate analysis and logistic regression. Despite presenting significantly fewer HPV risk factors, SLE patients were found to have a threefold increase in HPV infection, mostly genotypes 53, 58, 45, 66, 6, 84, 83, 61, as compared with controls, who presented types 6, 18 and 61 more frequently. The higher rate of HPV infection was associated with immunosuppressive therapy. This study provides evidence that SLE patients have a high prevalence of HPV infection, which is even higher with the use of IM, a condition that might necessitate a more frequent cervical cancer screening program for these women.

  14. Human papillomavirus (HPV) perinatal transmission and risk of HPV persistence among children: Design, methods and preliminary results of the HERITAGE study.

    Science.gov (United States)

    Trottier, Helen; Mayrand, Marie-Hélène; Coutlée, François; Monnier, Patricia; Laporte, Louise; Niyibizi, Joseph; Carceller, Ana-Maria; Fraser, William D; Brassard, Paul; Lacroix, Jacques; Francoeur, Diane; Bédard, Marie-Josée; Girard, Isabelle; Audibert, François

    2016-12-01

    Perinatal route of transmission of human papillomavirus (HPV) has been demonstrated in several small studies. We designed a large prospective cohort study (HERITAGE) to better understand perinatal HPV. The objective of this article is to present the study design and preliminary data. In the first phase of the study, we recruited 167 women in Montreal, Canada, during the first trimester of pregnancy. An additional 850 are currently being recruited in the ongoing phase. Cervicovaginal samples were obtained from mothers in the first trimester and tested for HPV DNA from 36 mucosal genotypes (and repeated in the third trimester for HPV-positive mothers). Placental samples were also taken for HPV DNA testing. Conjunctival, oral, pharyngeal and genital samples were collected for HPV DNA testing in children of HPV-positive mothers at every 3-6 months from birth until 2 years of age. Blood samples were collected in mother and children for HPV serology testing. We found a high prevalence of HPV in pregnant women (45%[95%CI:37-53%]) and in placentas (14%[8-21%]). The proportion of HPV positivity (any site) among children at birth/3-months was 11%[5-22%]. HPV was detected in children in multiple sites including the conjunctiva (5%[10-14%]). The ongoing HERITAGE cohort will help provide a better understanding of perinatal HPV. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Establishment of a Korea HPV cohort study

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    Lee, Won-Chul; Lee, Sae-Young; Koo, Yu Jin; Kim, Tae-Jin; Hur, Soo Young; Hong, Sung Ran; Kim, Sung Soon; Kee, Mee-Kyung; Rhee, Jee Eun; Lee, Joo Shil; Choi, Ho Sun; Cho, Chi Heum; Kim, Ki Tae

    2013-01-01

    We have designed a five-year multicentre prospective cohort study in women who are both human papillomavirus (HPV)-positive with either atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) of cervix. This study aimed to analyze the risk of developing a high-grade squamous intraepithelial lesion (HSIL) from either ASCUS or LSIL in HPV-positive women, so called 'progression' rate, to investigate differences in the progression rates according to HPV type-specific infection, and to evaluate the various factors associated with the persistence or clearance of HPV infection in the Korean population. At present, the study protocol composed of cervical cytology, HPV DNA testing, and questionnaire have been conducted actively since the first participant was enrolled in 2010. This study is the first nationwide Korea HPV cohort study. Our data will provide valuable information about not only the ambiguous cytology results of ASCUS and LSIL but also the effect of the specific HPV type and other various factors on the progression to HSIL. Finally, the results of our study will be helpful and applicable to determine the primary cervical cancer prevention strategies. PMID:23346315

  16. The clinical implementation of primary HPV screening.

    Science.gov (United States)

    Mariani, Luciano; Igidbashian, Sarah; Sandri, Maria Teresa; Vici, Patrizia; Landoni, Fabio

    2017-03-01

    To evaluate, from a gynecology perspective, the transition from cytology-based HPV screening to primary HPV screening. Studies examining switching from cytology-based screening to primary HPV-DNA testing with triaging of patients with positive test results were retrieved and reviewed, with a particular focus on screening in an Italian setting. The increased complexity of patient-management decisions when implementing HPV-based screening was a critical issue discussed in the literature. The change in strategy represents a paradigm shift in moving from a medical perspective of identifying the disease in individual patients, to a public-healthcare perspective of excluding HPV from the healthy population and identifying a small sub-group of individuals at increased risk of HPV. With knowledge about HPV screening evolving rapidly, new programs and related algorithms need to be sufficiently flexible to be adjusted according to ongoing research and the validation of new assays. The establishment of a national working group (including epidemiologists, gynecologists, pathologists, and healthcare providers) will be necessary to properly implement and govern this important technical and cultural transition. © 2016 International Federation of Gynecology and Obstetrics.

  17. Signature sequence validation of human papillomavirus type 16 (HPV-16) in clinical specimens.

    Science.gov (United States)

    Lee, Sin Hang; Vigliotti, Veronica S; Pappu, Suri

    2010-03-01

    Persistent infection indicated by detection of human papillomavirus 16 (HPV-16) on repeat testing over a period of time poses the greatest cervical cancer risk. However, variants of HPV-16, HPV-31 and HPV-33 may share several short sequence homologies in the hypervariable L1 gene commonly targeted for HPV genotyping. The purpose of this study was to introduce a robust laboratory procedure to validate HPV-16 detected in clinical specimens, using the GenBank sequence database as the standard reference for genotyping. A nested PCR with two pairs of consensus primers was used to amplify the HPV DNA released in crude proteinase K digest of the cervicovaginal cells in liquid-based Papanicolaou cytology specimens. The positive nested PCR products were used for direct automated DNA sequencing. A 48-base sequence downstream of the GP5+ priming site, or a 34-base sequence upstream thereof, was needed for unequivocal validation of an HPV-16 isolate. Selection of a 45-base, or shorter, sequence immediately downstream of the GP5+ site for Basic Local Alignment Search Tool sequence analysis invariably led to ambiguous genotyping results. DNA sequence analysis may be used for differential genotyping of HPV-16, HPV-31 and HPV-33 in clinical specimens. However, selection of the signature sequence for Basic Local Alignment Search Tool algorithms is crucial to distinguish certain HPV-16 variants from other closely related HPV genotypes.

  18. HPV (Human Papillomavirus)

    Science.gov (United States)

    ... Consumers Consumer Information by Audience For Women HPV (human papillomavirus) Share Tweet Linkedin Pin it More sharing ... Español In Chamorro In Urdu In Vietnamese HPV (human papillomavirus) is a sexually transmitted virus. It is ...

  19. La baja utilidad de la determinación del ADN del VPH en la región distal de la uretra masculina Low usefulness of HPV DNA determination in the distal region of the male urethra

    Directory of Open Access Journals (Sweden)

    Ahideé G Leyva-López

    2003-01-01

    Full Text Available OBJETIVO: Determinar la prevalencia uretral del ácido desoxirribonucleico del virus de papiloma humano, condilomatosis clínica y subclínica, en hombres cuyas parejas sexuales tuvieron el antecedente de neoplasia intraepitelial cervical. MATERIAL Y MÉTODOS: De octubre de 1997 a agosto de 1998 se hizo un estudio transversal; se incluyeron 200 hombres de entre 17 a 64 años de edad, referidos a la Coordinación de Oncología del Instituto Nacional de Perinatología, de la Ciudad de México, porque sus parejas regulares sexuales tuvieron el antecedente de neoplasia intraepitelial cervical. Se llevó a cabo un examen físico del pene (penoscopía con la aplicación de ácido acético a 3-5%, y con el uso de un colposcopio se localizaron y evaluaron zonas acetoblancas y cambios vasculares, interpretados como anormales, asociados con la infección por el virus del papiloma humano. La determinación del ADN de VPH se verificó por PCR e hibridación en línea reversa. El análisis estadístico exploratorio y univariante se realizó con el paquete Stata V6.0. RESULTADOS: En las 200 muestras recolectadas de células exfoliadas de la uretra el gen de beta-globina estuvo presente en 93.5% (187/200, y el ácido desoxirribonucleico del virus del papiloma humano fue detectable solamente en 2% (4/187 de los sujetos. Por medio de la penoscopía se observó la presencia de zonas acetoblancas en 43% (81/187 de los sujetos. CONCLUSIONES: En este estudio se observa que la presencia del ácido desoxirribonucleico del virus del papiloma humano en la uretra masculina es poco común, como lo reportan estudios internacionales. Es necesario realizar investigaciones que evalúen esta presencia en glande y surco balano prepucial, en comparación con la región distal de la uretra.OBJECTIVE: To assess the prevalence of Human Papillomavirus (HPV Deoxyribonucleic acid (DNA, and of clinical and subclinical condilomatosis in men whose sex partners had been diagnosed with

  20. Novel antitrypanosomal agents based on palladium nitrofurylthiosemicarbazone complexes: DNA and redox metabolism as potential therapeutic targets.

    Science.gov (United States)

    Otero, Lucía; Vieites, Marisol; Boiani, Lucía; Denicola, Ana; Rigol, Carolina; Opazo, Lucía; Olea-Azar, Claudio; Maya, Juan Diego; Morello, Antonio; Krauth-Siegel, R Luise; Piro, Oscar E; Castellano, Eduardo; González, Mercedes; Gambino, Dinorah; Cerecetto, Hugo

    2006-06-01

    In the search for new therapeutic tools against American Trypanosomiasis palladium complexes with bioactive nitrofuran-containing thiosemicarbazones as ligands were obtained. Sixteen novel palladium (II) complexes with the formulas [PdCl2(HL)] and [Pd(L)2] were synthesized, and the crystal structure of [Pd(5-nitrofuryl-3-acroleine thiosemicarbazone)2] x 3DMSO was solved by X-ray diffraction methods. Most complexes showed higher in vitro growth inhibition activity against Trypanosoma cruzi than the standard drug Nifurtimox. In most cases, the activity of the ligand was maintained or even increased as a result of palladium complexation. In addition, the complexes' mode of antitrypanosomal action was investigated. Although the complexes showed strong DNA binding, all data strongly suggest that the main trypanocidal mechanism of action is the production of oxidative stress as a result of their bioreduction and extensive redox cycling. Moreover, the complexes were found to be irreversible inhibitors of trypanothione reductase.

  1. Prioritizing multiple therapeutic targets in parallel using automated DNA-encoded library screening

    Science.gov (United States)

    Machutta, Carl A.; Kollmann, Christopher S.; Lind, Kenneth E.; Bai, Xiaopeng; Chan, Pan F.; Huang, Jianzhong; Ballell, Lluis; Belyanskaya, Svetlana; Besra, Gurdyal S.; Barros-Aguirre, David; Bates, Robert H.; Centrella, Paolo A.; Chang, Sandy S.; Chai, Jing; Choudhry, Anthony E.; Coffin, Aaron; Davie, Christopher P.; Deng, Hongfeng; Deng, Jianghe; Ding, Yun; Dodson, Jason W.; Fosbenner, David T.; Gao, Enoch N.; Graham, Taylor L.; Graybill, Todd L.; Ingraham, Karen; Johnson, Walter P.; King, Bryan W.; Kwiatkowski, Christopher R.; Lelièvre, Joël; Li, Yue; Liu, Xiaorong; Lu, Quinn; Lehr, Ruth; Mendoza-Losana, Alfonso; Martin, John; McCloskey, Lynn; McCormick, Patti; O'Keefe, Heather P.; O'Keeffe, Thomas; Pao, Christina; Phelps, Christopher B.; Qi, Hongwei; Rafferty, Keith; Scavello, Genaro S.; Steiginga, Matt S.; Sundersingh, Flora S.; Sweitzer, Sharon M.; Szewczuk, Lawrence M.; Taylor, Amy; Toh, May Fern; Wang, Juan; Wang, Minghui; Wilkins, Devan J.; Xia, Bing; Yao, Gang; Zhang, Jean; Zhou, Jingye; Donahue, Christine P.; Messer, Jeffrey A.; Holmes, David; Arico-Muendel, Christopher C.; Pope, Andrew J.; Gross, Jeffrey W.; Evindar, Ghotas

    2017-07-01

    The identification and prioritization of chemically tractable therapeutic targets is a significant challenge in the discovery of new medicines. We have developed a novel method that rapidly screens multiple proteins in parallel using DNA-encoded library technology (ELT). Initial efforts were focused on the efficient discovery of antibacterial leads against 119 targets from Acinetobacter baumannii and Staphylococcus aureus. The success of this effort led to the hypothesis that the relative number of ELT binders alone could be used to assess the ligandability of large sets of proteins. This concept was further explored by screening 42 targets from Mycobacterium tuberculosis. Active chemical series for six targets from our initial effort as well as three chemotypes for DHFR from M. tuberculosis are reported. The findings demonstrate that parallel ELT selections can be used to assess ligandability and highlight opportunities for successful lead and tool discovery.

  2. Evaluation of primary HPV-DNA testing in relation to visual inspection methods for cervical cancer screening in rural China: an epidemiologic and cost-effectiveness modelling study

    Directory of Open Access Journals (Sweden)

    Kang Yoon-Jung

    2011-06-01

    Full Text Available Abstract Background A new lower-cost rapid-throughput human papillomavirus (HPV test (careHPV, Qiagen, Gaithersburg, USA has been shown to have high sensitivity for the detection of high grade cervical intraepithelial neoplasia. Methods We assessed the outcomes and cost-effectiveness of careHPV screening in rural China, compared to visual inspection with acetic acid, when used alone (VIA or in combination with Lugol's iodine (VIA/VILI. Using data on sexual behaviour, test accuracy, diagnostic practices and costs from studies performed in rural China, we estimated the cost-effectiveness ratio (CER and associated lifetime outcomes for once-lifetime and twice-lifetime screening strategies, and for routine screening at 5-yearly, 10-yearly and IARC-recommended intervals. The optimal age range for once-lifetime screening was also assessed. Results For all strategies, the relative ordering of test technologies in reducing cervical cancer incidence and mortality was VIA (least effective; VIA/VILI; careHPV@1.0 pg/ml and careHPV@0.5 pg/ml (most effective. For once-lifetime strategies, maximum effectiveness was achieved if screening occurred between 35-50 years. Assuming a participation rate of ~70%, once-lifetime screening at age 35 years would reduce cancer mortality by 8% (for VIA to 12% (for careHPV@0.5 over the long term, with a CER of US$557 (for VIA to $959 (for careHPV@1.0 per life year saved (LYS compared to no intervention; referenced to a 2008 GDP per capita in Shanxi Province of $2,975. Correspondingly, regular screening with an age-standardised participation rate of 62% (which has been shown to be achievable in this setting would reduce cervical cancer mortality by 19-28% (for 10-yearly screening to 43-54% (using IARC-recommended intervals, with corresponding CERs ranging from $665 (for 10-yearly VIA to $2,269 (for IARC-recommended intervals using careHPV@1.0 per LYS. Conclusions This modelled analysis suggests that primary careHPV screening

  3. Development and Clinical Evaluation of a Highly Sensitive DNA Microarray for Detection and Genotyping of Human Papillomaviruses

    OpenAIRE

    Oh, TaeJeong; Kim, Changjin; Woo, SukKyung; Kim, TaeSeung; Jeong, Dongjun; Kim, MyungSoon; Lee, Sunwoo; Cho, HyunSill; An, Sungwhan

    2004-01-01

    Human papillomavirus (HPV) has been found in cervical cancer, tonsillar cancer, and certain types of head and neck cancers. We report on a DNA microarray-based method for the simultaneous detection and typing of HPVs. The genotype spectrum discriminated by this HPV DNA microarray includes 15 high-risk HPV genotypes and 12 low-risk HPV genotypes. The HPV DNA microarray showed high degrees of specificity and reproducibility. We evaluated the performance of the HPV DNA microarray by application ...

  4. Comparison of the immunogenicity of Cervarix(®) and Gardasil(®) human papillomavirus vaccines for oncogenic non-vaccine serotypes HPV-31, HPV-33, and HPV-45 in HIV-infected adults

    DEFF Research Database (Denmark)

    Toft, Lars; Tolstrup, Martin; Müller, Martin

    2014-01-01

    (®) (HPV-16/18, GlaxoSmithKline Biologicals, GSK) and Gardasil(®) (HPV-6/11/16/18, Merck) have demonstrated partial cross-protection against certain oncogenic non-vaccine HPV-types. Currently, there are no available data on vaccine-induced cross-protection in men and little is known about cross......Individuals infected with human immunodeficiency virus (HIV) have excess risk of developing human papillomavirus (HPV)-related disease. A substantial fraction of HPV-associated cancers is caused by HPV serotypes not included in the currently available vaccines. Among healthy women, both Cervarix......-reactive immunity after HPV-vaccination of HIV-infected individuals. In an investigator-initiated trial, we randomized 91 HIV-positive men and women to receive vaccination with Cervarix(®) or Gardasil(®). The HPV-DNA status of the participants was determined with pcr before and after immunization. Cross...

  5. [Investigation on HPV viral load and high risk HPV types infection among patients with infertility].

    Science.gov (United States)

    Zhang, Li-dong; Zhang, Hui-min; Pei, Jing; He, Gui-rong; Sun, Xiao-fang; Li, Bing

    2007-06-01

    High risk human papilomavirus (HPV) infection is often related to cervical cancer. This study investigated the infection of high risk HPV in cervical epithelia among infertile patients. Relative quantification and absolute quantification were applied for determination of "real" HPV viral load in the clinical setting. Adopting multi-channels real time PCR to genotype and quantify eight high risk HPV (HPV16, 18, 45, 31; intermediate risk types: HPV33, 52, 58, 67) DNA in cervical epithelia of the 130 infertile patients and the 150 controls. This study applied housekeeping gene (beta-globin) for the DNA quantification on secretions samples for clinical diagnosis. The infection rate of the infertility group was 25.38 percent (33/130) and that of the control group was 11.33 percent (17/150), the difference was statistically significant. Among the 33 positive cases in the infertility group, 24 cases showed a viral load no less than 106; in 9 of them, the viral load was less than 106. Among the 17 positive cases in the control group, 4 cases had a viral load no less than 106; in 13 of them, the viral load was less than 106. There is a statistically significant difference in viral load between the infertility group and the control group. The HPV infection rate of the infertility group was higher than that of the control group.

  6. Correlation between HPV status at T and N sites of oropharyngeal squamous cell carcinomas

    DEFF Research Database (Denmark)

    Josiassen, Michael Vallop; Charabi, Birgitte; Lajer, Christel Braemer

    2017-01-01

    Objectives: Human papilloma virus (HPV) is known to be associated with oropharyngeal squamous cell carcinomas (OPSCC) and may potentially play a vital role in tumor metastasis. The purpose of this study was to correlate HPV status of cervical lymph node metastases with their respective primary...... OPSCC tumor. Methods: Formalin-fixed, paraffin-embedded (FFPE) tissue samples obtained from 34 patients with cervical lymph node metastases were analyzed with HPV 16 DNA polymerase chain reaction (PCR), p16 immunohistochemistry and HPV typing. The results were correlated with the HPV status and type...... found in the primary tumors of OPSCC. Results: Comparing HPV DNA status with p16 we found that 21 primary tumors and lymph node metastases were HPV positive (61.8%) and seven primary tumors and lymph node metastases were HPV negative (20.6%). Six patient samples differed when correlating the primary...

  7. DNA and RNA aptamers: from tools for basic research towards therapeutic applications.

    Science.gov (United States)

    Ulrich, Henning; Trujillo, Cleber A; Nery, Arthur A; Alves, Janaina M; Majumder, Paromita; Resende, Rodrigo R; Martins, Antonio H

    2006-09-01

    The systematic evolution of ligands by exponential enrichment (SELEX) is a combinatorial oligonucleotide library-based in vitro selection approach in which DNA or RNA molecules are selected by their ability to bind their targets with high affinity and specificity, comparable to those of antibodies. Nucleic acids with high affinity for their targets have been selected against a wide variety of compounds, from small molecules, such as ATP, to membrane proteins and even whole organisms. Recently, the use of the SELEX technique was extended to isolate oligonucleotide ligands, also known as aptamers, for a wide range of proteins of importance for therapy and diagnostics, such as growth factors and cell surface antigens. The number of aptamers generated as inhibitors of various target proteins has increased following automatization of the SELEX process. Their diagnostic and therapeutic efficacy can be enhanced by introducing chemical modifications into the oligonucleotides to provide resistance against enzymatic degradation in body fluids. Several aptamers are currently being tested in preclinical and clinical trials, and aptamers are in the process of becoming a new class of therapeutic agents. Recently, the anti-VEGF aptamer pegaptanib received FDA approval for treatment of human ocular vascular disease.

  8. HPV prevalence in vulvar cancer in Austria.

    Science.gov (United States)

    Pils, Sophie; Gensthaler, Lisa; Alemany, Laia; Horvat, Reinhard; de Sanjosé, Silvia; Joura, Elmar A

    2017-11-01

    Even if vulvar cancer is not common, over one hundred women are affected in Austria per year. There is strong evidence that basaloid and warty variants are associated with types of human papillomavirus (HPV). The aim of this study is to analyze the types of HPV in vulvar cancer in Austria. This cross-sectional period-prevalence international collaborative study on archival specimens was performed in cooperation with the Institut Catalan di Oncologia in Barcelona, Spain. A total of 177 consecutive samples of Austrian women were analyzed to detect the presence of various HPV types using the SPF10 PCR/DEIA/LiPA25 system. Furthermore, the expression of the tumor suppressor protein p16(INK4a) was analyzed by immunohistochemistry (CINtec histology kit, ROCHE). A tumor was considered HPV-driven if an overexpression of p16(INK4a) was detected. In all, 41 cases of vulvar cancer tested positive for HPV DNA (23%) and 32 (18%) were p16 positive. Patients with warty and basaloid squamous cell cancer were significantly younger than those with keratinizing squamous cell cancer (63.3 years vs. 71.0 years, p = 0.021). In addition, 77.4% of all cases suffering from warty or basaloid squamous cell cancer tested positive for HPV, compared to 9.5% of the keratinizing squamous cell cancer cases (p HPV strain was type 16, followed by 31 and 33. Infection with HPV type 16 appears to be strongly correlated to the development of warty or basaloid squamous cell cancer. Vaccination against HPV can be expected to prevent this type of vulvar cancer.

  9. HPV for cervical cancer screening (HPV FOCAL): Complete Round 1 results of a randomized trial comparing HPV‐based primary screening to liquid‐based cytology for cervical cancer

    National Research Council Canada - National Science Library

    Ogilvie, Gina S; Krajden, Mel; van Niekerk, Dirk; Smith, Laurie W; Cook, Darrel; Ceballos, Kathy; Lee, Marette; Gentile, Laura; Gondara, Lovedeep; Elwood‐Martin, Ruth; Peacock, Stuart; Stuart, Gavin; Franco, Eduardo L; Coldman, Andrew J

    2017-01-01

    Complete Round 1 data (baseline and 12‐month follow‐up) for HPV FOCAL, a randomized trial establishing the efficacy of HPV DNA testing with cytology triage as a primary screen for cervical cancer are presented...

  10. Quantitation of Human Papillomavirus DNA in Plasma of Oropharyngeal Carcinoma Patients

    Energy Technology Data Exchange (ETDEWEB)

    Cao Hongbin; Banh, Alice [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Kwok, Shirley [Department of Pathology, Stanford University School of Medicine, Stanford, CA (United States); Shi Xiaoli; Wu, Simon; Krakow, Trevor; Khong, Brian; Bavan, Brindha [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Bala, Rajeev; Pinsky, Benjamin A. [Department of Pathology, Stanford University School of Medicine, Stanford, CA (United States); Colevas, Dimitrios [Department of Medicine, Stanford University School of Medicine, Stanford, CA (United States); Pourmand, Nader [Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA (United States); Koong, Albert C. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Kong, Christina S. [Department of Pathology, Stanford University School of Medicine, Stanford, CA (United States); Le, Quynh-Thu, E-mail: qle@stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States)

    2012-03-01

    Purpose: To determine whether human papillomavirus (HPV) DNA can be detected in the plasma of patients with HPV-positive oropharyngeal carcinoma (OPC) and to monitor its temporal change during radiotherapy. Methods and Materials: We used polymerase chain reaction to detect HPV DNA in the culture media of HPV-positive SCC90 and VU147T cells and the plasma of SCC90 and HeLa tumor-bearing mice, non-tumor-bearing controls, and those with HPV-negative tumors. We used real-time quantitative polymerase chain reaction to quantify the plasma HPV DNA in 40 HPV-positive OPC, 24 HPV-negative head-and-neck cancer patients and 10 non-cancer volunteers. The tumor HPV status was confirmed by p16{sup INK4a} staining and HPV16/18 polymerase chain reaction or HPV in situ hybridization. A total of 14 patients had serial plasma samples for HPV DNA quantification during radiotherapy. Results: HPV DNA was detectable in the plasma samples of SCC90- and HeLa-bearing mice but not in the controls. It was detected in 65% of the pretreatment plasma samples from HPV-positive OPC patients using E6/7 quantitative polymerase chain reaction. None of the HPV-negative head-and-neck cancer patients or non-cancer controls had detectable HPV DNA. The pretreatment plasma HPV DNA copy number correlated significantly with the nodal metabolic tumor volume (assessed using {sup 18}F-deoxyglucose positron emission tomography). The serial measurements in 14 patients showed a rapid decline in HPV DNA that had become undetectable at radiotherapy completion. In 3 patients, the HPV DNA level had increased to a discernable level at metastasis. Conclusions: Xenograft studies indicated that plasma HPV DNA is released from HPV-positive tumors. Circulating HPV DNA was detectable in most HPV-positive OPC patients. Thus, plasma HPV DNA might be a valuable tool for identifying relapse.

  11. Evaluation of the clinical performance of the Abbott RealTime High-Risk HPV for carcinogenic HPV detection.

    Science.gov (United States)

    Halfon, Philippe; Benmoura, Dominique; Agostini, Aubert; Khiri, Hacene; Penaranda, Guillaume; Martineau, Agnes; Blanc, Bernard

    2010-08-01

    Abbott RealTime (RT) High-Risk (HR) HPV assay is a new qualitative real-time polymerase chain reaction (PCR) based assay for the detection of 14 HR HPV DNA. The assay can differentiate between the infection by HPV 16, HPV 18 and non-HPV 16/18 types through the distinct fluorescent labels on the type specific probes. To evaluate the clinical performance of the Abbott RT HR HPV test, in comparison with biopsy, Hybrid Capture II (HCII), and Linear Array (LA), for detection of high-grade disease (CIN2+). The study population consisted of 143 women who were included in three referral gynecology clinics in Marseilles (France) between March 2007 and June 2008. The clinical performance of the RT HR HPV assay, performed on the fully automated m2000 system, was compared with HCII and LA. HR HPV positivity rate was similar for all tests (Abbott RT HR HPV and HCII, 62%, and LA 63%). All tests had high sensitivities and negative predictive values for CIN2+ detection (>90%). The agreement between HCII and Abbott RT HR HPV, and between HCII and LA were 93% (k=0.85) and 96% (k=0.91) respectively. As expected, HPV16 or HPV18 positivity was greater in advanced grades of disease, especially in CIN2+ patients: 85% in CIN2+ vs. 33% in Abbott RT HR HPV assay is good and closely correlated with the two other assays. The automation and ability to identify type 16 and 18 make this a very attractive option for HPV testing in laboratories and potentially provides improved patient management. Copyright 2010. Published by Elsevier B.V.

  12. Application of molecular genotyping to determine prevalence of HPV strains in Pap smears of Kazakhstan women

    OpenAIRE

    Niyazmetova, Luiza; Aimagambetova, Gulzhanat; Stambekova, Nazigul; Abugalieva, Zaurech; Seksembayeva, Korlukain; Ali, Syed; Azizan, Azliyati

    2017-01-01

    Objectives: Human papillomavirus is the main causative agent for cervical cancer. However, few data are available about HPV prevalence in Kazakhstan. The aims of this study were to genotype HPV DNA in Pap smear samples of women to determine prevalence of carcinogenic HPV types in Astana, Kazakhstan and to analyze the association between HPV positivity and the cytology results of patient samples. Methods: Pap smear materials were obtained from 140 patients aged 18-59, who visited the outpat...

  13. Prevalence of type-specific HPV infection in Uruguay.

    Science.gov (United States)

    Berois, Nora; Heard, Isabelle; Fort, Zoraida; Alonso, Rafael; Sica, Adela; Moerzinger, Patricia; Rodriguez, Guillermo; Sancho-Garnier, Hélène; Osinaga, Eduardo; Favre, Michel

    2014-04-01

    The aim of this work was to describe the prevalence of type-specific Human papillomavirus (HPV) infection in women attending organized cervical cancer screening program in Uruguay. Nine hundred sixty-five liquid cervical cell samples obtained after collection of cervical smears for cytology were assessed for HPV DNA using the Papillocheck system (Greiner BioOne). The overall prevalence of High-Risk (HR) HPV infections was 20.8% and increased from 16.5% in women with normal cytology to 93.3% in HSIL. Prevalence of HPV 16 and/or 18 was 6.3% and HPV 16 was the most prevalent genotype in normal cytology (3.6%). The five most prevalent genotypes were HPV 16, 31, 51, 56, and 39. The overall prevalence peaked below age 30. This study provides essential baseline information at national level on type-specific HPV prevalence in Uruguay before the introduction of HPV vaccination. It documents the current prevalence of each of the oncogenic genotypes in a population attending cervical cancer screening program, suggesting that at least 64.7% of high risk lesions are potentially preventable by available HPV vaccines, and possibly augmentable if cross-protection against non-vaccine HPV types 31, 33, and 45 is confirmed. © 2013 Wiley Periodicals, Inc.

  14. Prevalence and genotyping of HPV, by cervical brushing, in Irpinia area of Campania region

    Directory of Open Access Journals (Sweden)

    Pia Carmen Melillo

    2012-03-01

    Full Text Available Cervical cancer is due to persistent genital infection with Human Papillomavirus (HPV.The purpose of this study was to evaluate prevalence of HPV in Irpinia (Campania region, Italy, distribution of different viral genotypes, correlating cytological results and virological investigations. In the period 2006-2011, were made 1080 cervical samples of women aged 18-65 years for HPV identification and genotyping. Detection of the virus was performed by Multiplex-PCR System (Seegene,Arrow and typing with INNO-LiPA HPV Genotyping Extra test (Innogenetics. Out of the 1080 tested samples, 330 (30.6% samples were positive for HPV DNA. The most frequently occurring High Risk (HR-HPV genotype in single infections was HPV16 (16.6%, followed by HPV51 (10.7%, in multiple infections HPV16 (15.7% and 31 (14.6%. The prevalence of infection, correlated with age of patients studied, is greater in the group aged 26-30 years (42.5%. HR-HPV were detected in different percent in patients with Pap test scores: 22.5% in normal Pap smear (20% HPV16, 14.5% ASCUS (47.6% HPV16, 24% LSIL (20% HPV16, 79.3% HSIL (72.7% HPV16; 9.1% HPV18 detected only in this type of cellular alteration. The high prevalence of HR-HPV in patients with ASCUS or normal Pap test, suggesting the real advantage of HPV screening test, more sensitive in selecting the actual population at risk. Based on the findings of our epidemiological study, HR-HPV screening and HPV genotyping test should be strongly advised also to the vaccinated population for the high incidence of genotypes which are not included in vaccines (67%.

  15. Clinical Validation of the Abbott RealTime High Risk HPV Assay According to the Guidelines for Human Papillomavirus DNA Test Requirements for Cervical Screening

    OpenAIRE

    Hesselink, A. T.; Meijer, C J L M; Poljak, M.; Berkhof, J; van Kemenade, F. J.; van der Salm, M. L.; Bogaarts, M.; Snijders, P J F; Heideman, D. A. M.

    2013-01-01

    This study showed that the Abbott RealTime High Risk HPV assay fulfilled cross-sectional clinical equivalence and reproducibility criteria of international consensus guidelines, which indicates that this assay can be considered clinically validated for cervical cancer screening purposes.

  16. DermaVir: a plasmid DNA-based nanomedicine therapeutic vaccine for the treatment of HIV/AIDS.

    Science.gov (United States)

    Lori, Franco

    2011-10-01

    The HIV global pandemic continues to rage with over 33 million people living with the disease. Although multidrug therapy has improved the prognosis for those infected by the virus, it has not eradicated the infection. Immunological therapies, including therapeutic vaccines, are needed to supplement drug therapy in the search for a 'functional cure' for HIV. DermaVir (Genetic Immunity Kft, Budapest, Hungary and McLean, Virginia, USA), an experimental HIV/AIDS therapeutic vaccine, combines three key elements of rational therapeutic vaccine design: a single plasmid DNA (pDNA) immunogen expressing 15 HIV antigens, a synthetic pDNA nanomedicine formulation and a dendritic cell-targeting topical-vaccine administration. DermaVir's novel mechanism of action, natural transport by epidermal Langerhans cells to the lymph nodes to express the pDNA-encoded HIV antigens and induce precursor/memory T cells with high proliferation capacity, has been consistently demonstrated in mouse, rabbit, primate and human subjects. Safety, immunogenicity and preliminary efficacy of DermaVir have been clinically demonstrated in HIV-infected human subjects. The DermaVir technology platform for dendritic cell-based therapeutic vaccination might offer a new treatment paradigm for cancer and infectious diseases.

  17. Metabolism and function of hepatitis B virus cccDNA: Implications for the development of cccDNA-targeting antiviral therapeutics.

    Science.gov (United States)

    Guo, Ju-Tao; Guo, Haitao

    2015-10-01

    Persistent hepatitis B virus (HBV) infection relies on the stable maintenance and proper functioning of a nuclear episomal form of the viral genome called covalently closed circular (ccc) DNA. One of the major reasons for the failure of currently available antiviral therapeutics to achieve a cure of chronic HBV infection is their inability to eradicate or inactivate cccDNA. In this review article, we summarize our current understanding of cccDNA metabolism in hepatocytes and the modulation of cccDNA by host pathophysiological and immunological cues. Perspectives on the future investigation of cccDNA biology, as well as strategies and progress in therapeutic elimination and/or transcriptional silencing of cccDNA through rational design and phenotypic screenings, are also discussed. This article forms part of a symposium in Antiviral Research on "An unfinished story: from the discovery of the Australia antigen to the development of new curative therapies for hepatitis B." Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Prevalence of HPV 16 and 18 and attitudes toward HPV vaccination trials in patients with cervical cancer in Mali.

    Directory of Open Access Journals (Sweden)

    Ibrahima Téguété

    Full Text Available Cervical cancer is one of the most common and lethal cancers in West Africa. Even though vaccines that protect against the most common Human papillomavirus (HPV strains, 16 and 18, are currently in use in developed countries, the implementation of these vaccines in developing countries has been painfully slow, considering the pre-eminence of HPV-associated cervical cancer among women in those countries.We performed serological and PCR-based assessment of blood and tissue specimens obtained from women undergoing cervical cancer-related surgery at a major urban hospital in Bamako. Since several therapeutic HPV vaccines are currently in clinical trials, we also assessed willingness to participate in HPV cancer vaccine trials.Blood and biopsy samples of 240 women were evaluated for HPV types 16 and 18 by serology and PCR. Knowledge regarding the HPV vaccine and autonomy to decide to vaccinate their own child was assessed with a standardized questionnaire.HPV 16 and 18 were identified in 137/166 (82.5% cervical cancer biopsy samples by PCR. Co-infection with both HPV 16 and 18 was significantly more frequent in women over 50 years of age than in younger women (63.0% vs. 37.0%. 44% of study participants said they would be willing to vaccinate their child with HPV vaccine. Only 39% of women participating in this study reported that they would be able to make an autonomous decision to receive HPV vaccination. Permission from a male spouse or head of household was identified as important for participation by 59% of the women.This study provides strong support for the introduction of currently available HPV vaccines in Mali, and also provides key information about conditions for obtaining informed consent for HPV vaccine trials and HPV vaccination in Mali.

  19. Prevalence of HPV 16 and 18 and attitudes toward HPV vaccination trials in patients with cervical cancer in Mali.

    Science.gov (United States)

    Téguété, Ibrahima; Dolo, Amadou; Sangare, Kotou; Sissoko, Abdoulaye; Rochas, Mali; Beseme, Sarah; Tounkara, Karamoko; Yekta, Shahla; De Groot, Anne S; Koita, Ousmane A

    2017-01-01

    Cervical cancer is one of the most common and lethal cancers in West Africa. Even though vaccines that protect against the most common Human papillomavirus (HPV) strains, 16 and 18, are currently in use in developed countries, the implementation of these vaccines in developing countries has been painfully slow, considering the pre-eminence of HPV-associated cervical cancer among women in those countries. We performed serological and PCR-based assessment of blood and tissue specimens obtained from women undergoing cervical cancer-related surgery at a major urban hospital in Bamako. Since several therapeutic HPV vaccines are currently in clinical trials, we also assessed willingness to participate in HPV cancer vaccine trials. Blood and biopsy samples of 240 women were evaluated for HPV types 16 and 18 by serology and PCR. Knowledge regarding the HPV vaccine and autonomy to decide to vaccinate their own child was assessed with a standardized questionnaire. HPV 16 and 18 were identified in 137/166 (82.5%) cervical cancer biopsy samples by PCR. Co-infection with both HPV 16 and 18 was significantly more frequent in women over 50 years of age than in younger women (63.0% vs. 37.0%). 44% of study participants said they would be willing to vaccinate their child with HPV vaccine. Only 39% of women participating in this study reported that they would be able to make an autonomous decision to receive HPV vaccination. Permission from a male spouse or head of household was identified as important for participation by 59% of the women. This study provides strong support for the introduction of currently available HPV vaccines in Mali, and also provides key information about conditions for obtaining informed consent for HPV vaccine trials and HPV vaccination in Mali.

  20. Analytical performance of newly developed multiplex human papillomavirus genotyping assay using Luminex xMAP™ technology (Mebgen™ HPV Kit).

    Science.gov (United States)

    Ozaki, Satoru; Kato, Kana; Abe, Yukiko; Hara, Hirotaka; Kubota, Hiroshi; Kubushiro, Kaneyuki; Kawahara, Ei; Inoue, Masaki

    2014-08-01

    Regional differences in human papillomavirus (HPV) genotypes and the presence of mixed HPV infections may affect adversely the efficacy of the HPV vaccine. Therefore, a simple and high-throughput HPV genotyping system is required. Recently, a novel HPV genotyping kit (the Mebgen™ HPV kit) was developed. This kit uses multiplex PCR and Luminex xMAP™ technology to detect 13 types of high-risk HPVs and an internal control in a 96-well format. In the present study, the analytical performance of the kit was examined using HPV plasmid DNA. All 13 types of HPVs were detected with a minimum detection sensitivity of 250 copies/test, and highly specific signals were observed. HPV 16 plasmid was detected in samples containing mixtures with other HPV-type plasmids in ratios ranging from 1:1 to 1:1000. No cross reactivity was observed with DNA from 27 types of other infectious microbes. A clinical evaluation was carried out using cervical samples from 356 patients with persistent abnormal smears diagnosed at mass public health screenings for cervical cancer. The samples were preserved in Tacas™ medium until analysis. HPV was detected in 162 (45.5%) samples including 110 (67.9%) with single infections and 52 (32.1%) with multiple infections. The type distribution of the 13 high-risk HPVs was as follows: 28.4% HPV 16, 11.7% HPV 18, 6.8% HPV 31, 3.1% HPV 33, 3.7% HPV 35, 9.3% HPV 39, 1.9% HPV 45, 8.6% HPV 51, 37.0% HPV 52, 9.3% HPV 56, 16.7% HPV 58, 3.7% HPV 59, and 1.9% HPV 68. To evaluate sample stability over time, changes in the detection of HPV DNA derived from HeLa and SiHa cells were measured in 3 types of liquid-based cytology media. HPV DNA was detected in Tacas and Thinprep™ samples after storage at 4°C or 30°C for 4 weeks and within 1 week of collection in Surepath™ samples. These results suggest that this newly developed HPV genotyping kit is suitable for use in both clinical applications and large-scale epidemiological studies. Copyright © 2014 The

  1. Comparison of DRY and WET vaginal swabs with cervical specimens in Roche Cobas 4800 HPV and Abbott RealTime High Risk HPV tests.

    Science.gov (United States)

    Jun, Jae Kwan; Lim, Myong Cheol; Hwang, Sang-Hyun; Shin, Hye Young; Hwang, Na Rae; Kim, Yeon-Jin; Yoo, Chong Woo; Lee, Dong Ock; Joo, Jungnam; Park, Sang-Yoon; Lee, Do-Hoon

    2016-06-01

    Self-collected vaginal swab samples have been proposed as an alternative specimen collection method for human papillomavirus (HPV) DNA detection. Two vaginal swabs (a cone-shaped flocked swab (DRY) and a L-shape FLOQSwab with 2mL eNAT transport medium (WET)) were compared to standard cervical samples for HPV DNA testing. Additionally, they were also compared by using Roche Cobas 4800 HPV (Roche_HPV) and Abbott Real-time High Risk HPV (Abbott_HPV) tests. Ninety-six women were prospectively enrolled from the National Cancer Center in Korea between June and August 2015. WET and DRY vaginal swabs and cervical specimens were collected. Roche_HPV and Abbott_HPV tests were performed. The Roche_HPV test on cervical specimens was used as reference. The observed agreements (kappa) of Roche_HPV and Abbott_HPV between WET and DRY swabs were 89.6% (0.790, 95% confidence interval (95% CI): 0.667-0.913) and 91.7% (0.833, 95%CI: 0.723-0.943), respectively. No statistical difference was observed between WET and DRY swabs (p>0.05 for all comparisons). For HPV16/18, the sensitivity/specificity of Roche_HPV on the DRY and WET samples presented 93.8%/96.3% and 87.5%/97.5%, respectively. For other High Risk HPV (hrHPV), the sensitivity/specificity of Roche_HPV on the DRY and WET swabs presented 91.9%/91.5% and 97.3%/98.3, respectively. The sensitivity/specificity of the Abbott_HPV on the DRY and WET swabs were 93.8%/98.8%, 87.5%/98.8% for HPV16/18, and 91.9%/93.2%, 100.0%/93.2% for other hrHPV, respectively. HPV tests performed similarly when using vaginal DRY and WET swab samples. Using DRY and WET swabs to collect vaginal specimens could be an alternative to collecting cervical samples for HPV DNA testing. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. HPV Infection in Men

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    Joel M. Palefsky

    2007-01-01

    Full Text Available While much is known about the natural history of cervical human papillomavirus (HPV infection and its consequences, including cervical intraepithelial neoplasia and cervical cancer, relatively little is known about the natural history of anogenital HPV infection and diseases in men. In part this reflects difficulties in penile sampling and visual assessment of penile lesions. Anal HPV infection and disease also remain poorly understood. Although HPV is transmitted sexually and infects the genitals of both sexes, the cervix remains biologically more vulnerable to malignant transformation than does the penis or anus in men. An understanding of male HPV infection is therefore important in terms of reducing transmission of HPV to women and improving women's health. However, it is also important due to the burden of disease in men, who may develop both penile and anal cancer, particularly among HIV-positive men who have sex with men. Improved sampling techniques of the male genitalia and cohort studies in progress should provide important information on the natural history of anogenital HPV infection and disease in men, including risk factors for HPV acquisition and transmission. The impact of HPV vaccination in women on male anogenital HPV infection will also need to be assessed.

  3. Genome-wide DNA polymorphisms in Kavuni, a traditional rice cultivar with nutritional and therapeutic properties.

    Science.gov (United States)

    Rathinasabapathi, Pasupathi; Purushothaman, Natarajan; Parani, Madasamy

    2016-05-01

    Although rice genome was sequenced in the year 2002, efforts in resequencing the large number of available accessions, landraces, traditional cultivars, and improved varieties of this important food crop are limited. We have initiated resequencing of the traditional cultivars from India. Kavuni is an important traditional rice cultivar from South India that attracts premium price for its nutritional and therapeutic properties. Whole-genome sequencing of Kavuni using Illumina platform and SNPs analysis using Nipponbare reference genome identified 1 150 711 SNPs of which 377 381 SNPs were located in the genic regions. Non-synonymous SNPs (62 708) were distributed in 19 251 genes, and their number varied between 1 and 115 per gene. Large-effect DNA polymorphisms (7769) were present in 3475 genes. Pathway mapping of these polymorphisms revealed the involvement of genes related to carbohydrate metabolism, translation, protein-folding, and cell death. Analysis of the starch biosynthesis related genes revealed that the granule-bound starch synthase I gene had T/G SNPs at the first intron/exon junction and a two-nucleotide combination, which were reported to favour high amylose content and low glycemic index. The present study provided a valuable genomics resource to study the rice varieties with nutritional and medicinal properties.

  4. HPV-Associated Cancers Statistics

    Science.gov (United States)

    ... Are Linked with HPV Each Year? Rates by Race and Ethnicity HPV-Associated Anal Cancer HPV-Associated ... file ePub file RIS file Page last reviewed: March 6, 2017 Page last updated: March 6, 2017 ...

  5. Primary screening for cervical cancer based on high-risk human papillomavirus (HPV) detection and HPV 16 and HPV 18 genotyping, in comparison to cytology.

    Science.gov (United States)

    Agorastos, Theodoros; Chatzistamatiou, Kimon; Katsamagkas, Taxiarchis; Koliopoulos, George; Daponte, Alexandros; Constantinidis, Theocharis; Constantinidis, Theodoros C

    2015-01-01

    The objective of the present study is to assess the performance of a high-risk human papillomavirus (HR-HPV) DNA test with individual HPV-16/HPV-18 genotyping as a method for primary cervical cancer screening compared with liquid-based cytology (LBC) in a population of Greek women taking part in routine cervical cancer screening. The study, conducted by the "HEllenic Real life Multicentric cErvical Screening" (HERMES) study group, involved the recruitment of 4,009 women, aged 25-55, who took part in routine cervical screening at nine Gynecology Departments in Greece. At first visit cervical specimens were collected for LBC and HPV testing using the Roche Cobas 4800 system. Women found positive for either cytology or HPV were referred for colposcopy, whereas women negative for both tests will be retested after three years. The study is ongoing and the results of the first screening round are reported herein. Valid results for cytology and HPV testing were obtained for 3,993 women. The overall prevalence of HR-HPV was 12.7%, of HPV-16 2.7% and of HPV-18 1.4%. Of those referred for colposcopy, cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was detected in 41 women (1.07%). At the threshold of CIN2+, cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] and HPV testing showed a sensitivity of 53.7% and 100% respectively, without change between age groups. Cytology and HPV testing showed specificity of 96.8% and 90.3% respectively, which was increased in older women (≥30) in comparison to younger ones (25-29). Genotyping for HPV16/18 had similar accuracy to cytology for the detection of CIN2+ (sensitivity: 58.5%; specificity 97.5%) as well as for triage to colposcopy (sensitivity: 58.5% vs 53.7% for cytology). HPV testing has much better sensitivity than cytology to identify high-grade cervical lesions with slightly lower specificity. HPV testing with individual HPV-16/HPV-18 genotyping could represent a more accurate

  6. Primary Screening for Cervical Cancer Based on High-Risk Human Papillomavirus (HPV) Detection and HPV 16 and HPV 18 Genotyping, in Comparison to Cytology

    Science.gov (United States)

    Constantinidis, Theocharis; Constantinidis, Theodoros C.

    2015-01-01

    Objectives The objective of the present study is to assess the performance of a high-risk human papillomavirus (HR-HPV) DNA test with individual HPV-16/HPV-18 genotyping as a method for primary cervical cancer screening compared with liquid-based cytology (LBC) in a population of Greek women taking part in routine cervical cancer screening. Methods The study, conducted by the “HEllenic Real life Multicentric cErvical Screening” (HERMES) study group, involved the recruitment of 4,009 women, aged 25–55, who took part in routine cervical screening at nine Gynecology Departments in Greece. At first visit cervical specimens were collected for LBC and HPV testing using the Roche Cobas 4800 system. Women found positive for either cytology or HPV were referred for colposcopy, whereas women negative for both tests will be retested after three years. The study is ongoing and the results of the first screening round are reported herein. Results Valid results for cytology and HPV testing were obtained for 3,993 women. The overall prevalence of HR-HPV was 12.7%, of HPV-16 2.7% and of HPV-18 1.4%. Of those referred for colposcopy, cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was detected in 41 women (1.07%). At the threshold of CIN2+, cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] and HPV testing showed a sensitivity of 53.7% and 100% respectively, without change between age groups. Cytology and HPV testing showed specificity of 96.8% and 90.3% respectively, which was increased in older women (≥30) in comparison to younger ones (25–29). Genotyping for HPV16/18 had similar accuracy to cytology for the detection of CIN2+ (sensitivity: 58.5%; specificity 97.5%) as well as for triage to colposcopy (sensitivity: 58.5% vs 53.7% for cytology). Conclusion HPV testing has much better sensitivity than cytology to identify high-grade cervical lesions with slightly lower specificity. HPV testing with individual HPV-16/HPV-18

  7. [HPV (Human Papilloma Virus) implication in other cancers than gynaecological].

    Science.gov (United States)

    Badoual, C; Tartour, E; Roussel, H; Bats, A S; Pavie, J; Pernot, S; Weiss, L; Mohamed, A Si; Thariat, J; Hoffmann, C; Péré, H

    2015-08-01

    Worldwide, approximately 5 to 10% of the population is infected by a Human Papilloma Virus (HPV). Some of these viruses, with a high oncogenic risk (HPV HR), are responsible for about 5% of cancer. It is now accepted that almost all carcinomas of the cervix and the vulva are due to an HPV HR (HPV16 and 18) infection. However, these viruses are known to be involved in the carcinogenesis of many other cancers (head and neck [SCCHN], penis, anus). For head and neck cancer, HPV infection is considered as a good prognostic factor. The role of HPV HR in anal cancer is also extensively studied in high-risk patient's population. The role of HPV infection in the carcinogenesis of esophageal, bladder, lung, breast or skin cancers is still debated. Given the multiple possible locations of HPV HR infection, the question of optimizing the management of patients with a HPV+ cancer arises in the implementation of a comprehensive clinical and biological monitoring. It is the same in therapeutics with the existence of a preventive vaccination, for example. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  8. [Developments in HPV vaccination].

    Science.gov (United States)

    de Melker, Hester; Kenter, Gemma; van Rossum, Tekla; Conyn-van Spaendonck, Marina

    2012-01-01

    Vaccination against the human papilloma virus (HPV) has been included in the national Vaccination Programme of the Netherlands for 12-year-old girls since 2010. Vaccination coverage for the birth cohort of 1997 was 56.; there is a gradual increase in uptake. Continuous safety monitoring brought no new unknown serious side effects to light; many girls suffered from transient symptoms such as painful arm, fatigue and headache. After the current vaccines that protect against HPV types 2 and 4 types, respectively and induce some cross protection, vaccines are being developed that can induce broader protection. HPV vaccination of 12-year-old girls is cost-effective, even for relatively low vaccination coverage. The potential protection of HPV vaccination extends beyond prevention of cervical cancer by preventing other oncological manifestations of HPV infection in women as well as men and genital warts. The preventive HPV vaccines do not appear to be effective in treating existing abnormalities.

  9. Enhanced Th1 and Th2 immune response induction by Human Papilloma virus Type 16 E7 DNA vaccine in a tumoric murine model

    Directory of Open Access Journals (Sweden)

    Alireza Mohebbi

    2017-01-01

    Full Text Available Background and Objectives: Human papilloma virus (HPV is known as the etiologic agent of cervical cancer and second common cancer among women. HPV viruses with the elevated risk of infection have more potentiality to cause cancer. The carcinogenesis in these viruses is accomplished by oncoproteins such as E7. Employing DNA vaccines which code specific antigens such as E7 is a novel therapeutic approach against such cancers. Methods: In the present study, plasmid coding HPV16 E7 was administered intracutaneously to C57BL/6 tumoric mice models for investigation of its immunostimulating potential. PcDNA3.1+ vector was used as control vector. After immunization, spleen of animals were removed. Then, release of lactate dehydrogenase (LDH was evaluated to address the cytotoxic activity (CTL induced by cellular immunity in spleenocytes. Interferon-γ (IFN-γ and interleukin-4 (IL-4 cytokines were also analyzed as profiles of Th1 and Th2, respectively. Anti-inflammatory cytokine interleukin-10 (IL-10 levels were also investigated in tumor microenvironments. Results: Our results showed that CTL activity was higher among samples receiving HPV16 E7 coding vector in comparison to the group receiving pcDNA3.1+ control vector (P < 0.05. Levels of IFN-γ and IL-4 were also higher in the group receiving HPV16 E7 plasmid in comparison to the control group (P < 0.05. Similarly, IL-10 levels were significantly lower in tumor carrying mice groups receiving HPV16 DNA vaccine compare to PBS and pcDNA3.1 receiving control groups. Conclusion: HPV16 E7 expressing DNA vaccine could increase the release of LDH due to immune system CTL activity. Elevation in IFN-γ and IL-4 levels as well as IL-10 reduction indicates an increase in both Th1 and Th2 profiles resulted by using potent DNA vaccine coding HPV16 E7 in tumor animal model.

  10. Human papillomavirus (HPV) in vulvar dysplasia and carcinoma in situ

    DEFF Research Database (Denmark)

    Junge, Jette; Poulsen, H; Horn, T

    1995-01-01

    whereas no case of pure basaloid type was found. Various combinations of warty and basaloid types were shown in 52 cases and mixed forms in 7 cases. The results indicate that pure forms of warty and basaloid types probably do not exist. HPV DNA was detected by PCR in 51/58 cases (88%) (45 with HPV type 16...... and 6 with HPV type 33) evenly distributed in all age groups and in all types of lesions (WHO and Toki et al. 1991). By ISH HPV was detected in 24/62 cases (39%) (21 with HPV type 16/18 and 3 with HPV type 31/33), nearly always in warty areas. All these cases were positive for the same virus type by PCR....... No case revealed more than one type of HPV. HPV type 6, 11, 18, and 31 were not detected by PCR. The results indicate a correlation between HPV type 16 and 33 and dysplasia/carcinoma in situ in the vulva....

  11. Berberine modulates AP-1 activity to suppress HPV transcription and downstream signaling to induce growth arrest and apoptosis in cervical cancer cells

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    Husain Syed A

    2011-04-01

    Full Text Available Abstract Background- Specific types of high risk Human papillomaviruses (HR-HPVs particularly, HPV types 16 and 18 cause cervical cancer and while the two recently developed vaccines against these HPV types are prophylactic in nature, therapeutic options for treatment and management of already existing HPV infection are not available as yet. Because transcription factor, Activator Protein-1 (AP-1 plays a central role in HPV-mediated cervical carcinogenesis, we explored the possibility of its therapeutic targeting by berberine, a natural alkaloid derived from a medicinal plant species, Berberis which has been shown to possess anti-inflammatory and anti-cancer properties with no known toxicity; however, the effect of berberine against HPV has not been elucidated. Results- We studied the effect of berberine on HPV16-positive cervical cancer cell line, SiHa and HPV18-positive cervical cancer cell line, HeLa using electrophoretic mobility gel shift assays, western and northern blotting which showed that berberine could selectively inhibit constitutively activated AP-1 in a dose- and time-dependent manner and downregulates HPV oncogenes expression. Inhibition of AP-1 was also accompanied by changes in the composition of their DNA-binding complex. Berberine specifically downregulated expression of oncogenic c-Fos which was also absent in the AP-1 binding complex. Treatment with berberine resulted in repression of E6 and E7 levels and concomitant increase in p53 and Rb expression in both cell types. Berberine also suppressed expression of telomerase protein, hTERT, which translated into growth inhibition of cervical cancer cells. Interestingly, a higher concentration of berberine was found to reduce the cell viability through mitochondria-mediated pathway and induce apoptosis by activating caspase-3. Conclusion- These results indicate that berberine can effectively target both the host and viral factors responsible for development of cervical cancer

  12. Prevalence of HPV infection among females in the United States.

    Science.gov (United States)

    Dunne, Eileen F; Unger, Elizabeth R; Sternberg, Maya; McQuillan, Geraldine; Swan, David C; Patel, Sonya S; Markowitz, Lauri E

    2007-02-28

    Human papillomavirus (HPV) infection is estimated to be the most common sexually transmitted infection. Baseline population prevalence data for HPV infection in the United States before widespread availability of a prophylactic HPV vaccine would be useful. To determine the prevalence of HPV among females in the United States. The National Health and Nutrition Examination Survey (NHANES) uses a representative sample of the US noninstitutionalized civilian population. Females aged 14 to 59 years who were interviewed at home for NHANES 2003-2004 were examined in a mobile examination center and provided a self-collected vaginal swab specimen. Swabs were analyzed for HPV DNA by L1 consensus polymerase chain reaction followed by type-specific hybridization. Demographic and sexual behavior information was obtained from all participants. HPV prevalence by polymerase chain reaction. The overall HPV prevalence was 26.8% (95% confidence interval [CI], 23.3%-30.9%) among US females aged 14 to 59 years (n = 1921). HPV prevalence was 24.5% (95% CI, 19.6%-30.5%) among females aged 14 to 19 years, 44.8% (95% CI, 36.3%-55.3%) among women aged 20 to 24 years, 27.4% (95% CI, 21.9%-34.2%) among women aged 25 to 29 years, 27.5% (95% CI, 20.8%-36.4%) among women aged 30 to 39 years, 25.2% (95% CI, 19.7%-32.2%) among women aged 40 to 49 years, and 19.6% (95% CI, 14.3%-26.8%) among women aged 50 to 59 years. There was a statistically significant trend for increasing HPV prevalence with each year of age from 14 to 24 years (PHPV vaccine types 6 and 11 (low-risk types) and 16 and 18 (high-risk types) were detected in 3.4% of female participants; HPV-6 was detected in 1.3% (95% CI, 0.8%-2.3%), HPV-11 in 0.1% (95% CI, 0.03%-0.3%), HPV-16 in 1.5% (95% CI, 0.9%-2.6%), and HPV-18 in 0.8% (95% CI, 0.4%-1.5%) of female participants. Independent risk factors for HPV detection were age, marital status, and increasing numbers of lifetime and recent sex partners. HPV is common among females in the

  13. Y Chromosome DNA in Women's Vaginal Samples as a Biomarker of Recent Vaginal Sex and Condom Use With Male Partners in the HPV Infection and Transmission Among Couples Through Heterosexual Activity Cohort Study.

    Science.gov (United States)

    Malagón, Talía; Burchell, Ann; El-Zein, Mariam; Guénoun, Julie; Tellier, Pierre-Paul; Coutlée, François; Franco, Eduardo L

    2017-08-04

    Y chromosome DNA from male epithelial and sperm cells was detected in vaginal samples after unprotected sex in experimental studies. We assessed the strength of this association in an observational setting to examine the utility of Y chromosome DNA as a biomarker of recent sexual behaviors in epidemiological studies. The HPV (human papillomavirus) Infection and Transmission Among Couples Through Heterosexual Activity cohort study enrolled 502 women attending a university or college in Montréal, Canada, and their male partners from 2005 to 2010. Participants completed self-administered questionnaires. We used real-time polymerase chain reaction to test women's baseline vaginal samples for Y chromosome DNA and assessed which sexual behaviors were independent predictors of Y chromosome DNA positivity and quantity with logistic and negative binomial regression. Y chromosome DNA positivity decreased from 77% in women in partnerships reporting vaginal sex 0 to 1 day ago to 13% in women in partnerships reporting last vaginal sex of 15 or more days ago (adjusted odds ratio, 0.09; 95% confidence interval, 0.02-0.36). The mean proportion of exfoliated vaginal sample cells with Y chromosome DNA was much lower for women who reported always using condoms (0.01%) than for women who reported never using condoms (2.07%) (adjusted ratio, 26.8; 95% confidence interval, 8.9-80.5). No association was found with reported oral/digital sex frequency or concurrency of partnerships. Y chromosome DNA quantity is strongly associated with days since last vaginal sex and lack of condom use in observational settings. Y chromosome DNA quantity may prove useful as a correlate of recent vaginal sex in observational studies lacking data on sexual behavior, such as surveillance studies of human papillomavirus infection prevalence.

  14. Cytohistological discrepancies of cervico-vaginal smears and HPV status.

    Science.gov (United States)

    Alanbay, İbrahim; Öztürk, Mustafa; Fıratlıgil, Fahri Burçin; Karaşahin, Kazım Emre; Yenen, Müfit Cemal; Bodur, Serkan

    2017-01-01

    Discrepancies between abnormal cervical cytology or high-risk human papillomavirus (HR-HPV) status (cytolo-gy negative/HPV positive) and subsequent histological findings are a common occurrence. After using co-testing, the dis-crepancies between the HR-HPV status and cervical cytology have become an issue. In this study, we aimed to determine the characteristics of women with a discrepancy between histology and cytology/HR-HPV status, in terms of diagnosis, review and identification. A total of 52 women, patients of the University Hospital between 2013-2015, with cytohistologi-cal or HR-HPV status discrepancy were recruited for the study and retrospectively analyzed. The cytological samples were liquid-based Pap smears, classified according to the 2001 Bethesda system. The HR-HPV status was identified using the Hybrid Capture 2 HR-HPV DNA assay. The histological samples were obtained by cervical biopsy as well as large loop exci-sion of the transformation zone (LLETZ). A cytohistological discrepancy was demonstrated in patients with (-)cytology/HR-HPV(+), ASCUS, LSIL, ASC-H, HSIL, AGC-NOS: 17.3%, 23.07%, 26.9%, 9.5%, 17.3% and 5.7%, respectively. When the degree of atypia in cytology increases, the concurrency of cervical cytology with biopsy also increases. A positive HR-HPV co-test result (19/24, 79.1%) was observed in nearly all CIN2 ≥ (+) cases. Our study emphasizes the significance of HR-HPV testing to determine CIN2 ≥ (+) cases, even in the presence of a normal cytological result. In case of cytohistological or HR-HPV discrepancies, a careful review of the HR-HPV status and the degree of cytological atypia should be performed before further intervention.

  15. HPV in HIV-Infected Women: Implications for Primary Prevention

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    Nathalie Dauphin Mckenzie

    2014-08-01

    Full Text Available Background: There is growing evidence that HIV-infected women might have a different HPV type distribution in cervical dysplasia specimens as compared to the general population. This has implications for primary prevention.Objective: We aimed to obtain preliminary data on the human papillomavirus (HPV genotypes prevalent in histological samples of HIV-infected women with CIN 3/ CIS of the cervix in Miami, Florida. Method: Retrospective data were collected on HIV-infected women referred to the UM-JMH colposcopy clinic between years 2000 and 2008. The histology slides of CIN3/CIS biopsies underwent pathological review and sections were cut from these archived specimens for HPV DNA extraction. HPV genotyping was then performed using the GeneSquare™ HPV genotyping assay. We report on our first set of 23 samples.Results: Eight high risk HPV (HR-HPV types were detected. Types in decreasing order of frequency were 16, 35, 45, 52, 59, 31, 58, and 56. Most cases had multiple infections. HPV type 16 was the most common (45% followed by HPV-35 and -45 with equal frequency (40%. No samples contained HPV-18Conclusion: Our preliminary data suggest that cervical dysplasia specimens of HIV-infected women more likely (55% contain non -16 and -18 high risk HPV types. We show that this held true for histologically confirmed carcinoma in situ. Epidemiological studies guide vaccine development, therefore HPV type prevalence in CIS and invasive cervical cancer among HIV-infected women should be more rigorously explored to ensure that this highly vulnerable population receives appropriate primary prevention.

  16. Outcomes of HPV-related nasal squamous cell carcinoma.

    Science.gov (United States)

    Chowdhury, Naweed; Alvi, Sameer; Kimura, Kyle; Tawfik, Ossama; Manna, Pradip; Beahm, David; Robinson, Ann; Kerley, Spencer; Hoover, Larry

    2017-07-01

    Human papilloma virus (HPV) infection has been shown to play an integral role in the development and prognosis of various head and neck cancers. Generational changes in sexual behavior may have led to an increased incidence of positivity in recent years. HPV positivity in both benign and malignant lesions of the sinonasal cavities has been shown in previous studies (estimates range from 20%-30% for malignancy). We intend to investigate if HPV positivity affected survival outcomes in our patient cohort. Twenty-six patients diagnosed pathologically for sinonasal squamous cell carcinoma (SCC) with available archived biopsy specimens were retrospectively analyzed to obtain HPV status using a real-time, multiplex polymerase chain reaction assay that detects and quantifies 15 known high-risk HPV types. Demographic information was collected, and survival analyses were performed using the Kaplan-Meier estimation. Sixteen of 26 (62%) SCC tumors in the patient cohort were positive for HPV DNA. HPV types 16 and 18 were the most common (n = 8 and 2, respectively), although a wide range of HPV types across the 15 tested were positive. Survival analyses showed a statistically significant survival advantage (median survival of 12 vs. 54 months) when accounting for HPV positivity using log-rank testing (P HPV positivity appears to be present in a significant proportion of squamous cell carcinoma cases of the nasal cavity. In our limited patient population there does appear to be a survival advantage to HPV positivity. Further prospective, multi-institutional trials with standardized treatment protocols are needed to elucidate the true impact of HPV positivity in this subset of head and neck cancers. 4. Laryngoscope, 127:1600-1603, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  17. Characterisation of human papillomavirus (HPV) genotypes in the Azorean population, Terceira island.

    Science.gov (United States)

    Dutra, Isa; Santos, Margarida R; Soares, Marta; Couto, Ana R; Bruges-Armas, Maria; Teixeira, Fernando; Monjardino, Luísa; Hodgson, Shirley; Bruges-Armas, Jácome

    2008-04-21

    Human papillomavirus detection is very important for the evaluation of prevention strategies in cervical cancer. In the Azorean population, the virus prevalence has never been studied, and there is no data available to preview a successful outcome with HPV vaccination. In this article, our objective is to characterise the HPV genotypes in Terceira Island, contributing for the epidemiological knowledge on the virus infection. Cervical samples were collected from 289 women aged 16-81 in the Gynaecological Outpatient Clinic of the Hospital de Santo Espírito de Angra do Heroísmo (HSEAH). HPV DNA was amplified by Polymerase Chain Reaction using the general consensus primers PGMYO9/PGMY11. Commercially available Papillomavirus Clinical Arrays kits (Genomica) were used to perform HPV genotyping. 30 women were HPV positive, with a median age of 41 years old. Our results show that the overall HPV prevalence was 10.49%. Seventeen genotypes were identified, including 58.82% high risk, 17.65% low risk and 23.53% undetermined risk. Unlike other epidemiological studies, HPV31 was the most frequent type (26.67%) in Terceira Island, followed by HPV16 (10.00%), HPV51, HPV53, HPV70 and HPV82 (6.67%). Further studies are needed to investigate if the HPV types found in our population are associated with the risk of progression to high-grade squamous intraepithelial lesions or cervical cancer.

  18. Characterisation of human papillomavirus (HPV genotypes in the Azorean population, Terceira island

    Directory of Open Access Journals (Sweden)

    Teixeira Fernando

    2008-04-01

    Full Text Available Abstract Background Human papillomavirus detection is very important for the evaluation of prevention strategies in cervical cancer. In the Azorean population, the virus prevalence has never been studied, and there is no data available to preview a successful outcome with HPV vaccination. In this article, our objective is to characterise the HPV genotypes in Terceira Island, contributing for the epidemiological knowledge on the virus infection. Results Cervical samples were collected from 289 women aged 16–81 in the Gynaecological Outpatient Clinic of the Hospital de Santo Espírito de Angra do Heroísmo (HSEAH. HPV DNA was amplified by Polymerase Chain Reaction using the general consensus primers PGMYO9/PGMY11. Commercially available Papillomavirus Clinical Arrays® kits (Genomica were used to perform HPV genotyping. 30 women were HPV positive, with a median age of 41 years old. Our results show that the overall HPV prevalence was 10.49%. Seventeen genotypes were identified, including 58.82% high risk, 17.65% low risk and 23.53% undetermined risk. Conclusion Unlike other epidemiological studies, HPV31 was the most frequent type (26.67% in Terceira Island, followed by HPV16 (10.00%, HPV51, HPV53, HPV70 and HPV82 (6.67%. Further studies are needed to investigate if the HPV types found in our population are associated with the risk of progression to high-grade squamous intraepithelial lesions or cervical cancer.

  19. Integrative analyses reveal novel strategies in HPV11,-16 and-45 early infection

    DEFF Research Database (Denmark)

    Kaczkowski, Bogumil; Rossing, Maria; Andersen, Ditte

    2012-01-01

    The interaction between human papillomavirus (HPV) and host cells is not well understood. We investigate the early stage of HPV infections by global expression profiling in a cell model, in which HaCaT cells were transfected with HPV11, HPV16 or HPV45 genomes. We report the differential expression...... of genes not previously implicated in HPV biology, such as the PSG family and ANKRD1, and of genes implicated in the biology of other viruses, e. g. MX1, IFI44 and DDX60. Carcinogenesis-related genes, e. g. ABL2, MGLL and CYR61, were upregulated by high-risk HPV16 and -45. The integrative analysis revealed...... the suppression of DNA repair by HPV11 and -16, and downregulation of cytoskeleton genes by all HPV types. Various signalling pathways were affected by the HPVs: IL-2 by HPV11; JAK-STAT by HPV16; and TGF-beta, NOTCH and tyrosine kinase signalling by HPV45. This study uncovered novel strategies employed by HPV...

  20. Comparison of the performance in detection of HPV infections between the high-risk HPV genotyping real time PCR and the PCR-reverse dot blot assays.

    Science.gov (United States)

    Zhang, Lahong; Dai, Yibei; Chen, Jiahuan; Hong, Liquan; Liu, Yuhua; Ke, Qiang; Chen, Yiwen; Cai, Chengsong; Liu, Xia; Chen, Zhaojun

    2018-01-01

    A new multiplex real-time PCR assay, the high-risk HPV genotyping real time PCR assay (HR HPV RT-PCR), has been developed to detect 15 high-risk HPV types with respective viral loads. In this report, a total of 684 cervical specimens from women diagnosed with vaginitis were assessed by the HR HPV RT-PCR and the PCR reaction and reverse dot blot (PCR-RDB) assays, using a PCR-sequencing method as a reference standard. A total coincidence of 97.7% between the HR HPV RT PCR and the PCR-RDB assays was determined with a Kappa value of 0.953. The HR HPV RT PCR assay had sensitivity, specificity, and concordance rates (accuracy) of 99.7%, 99.7%, and 99.7%, respectively, as confirmed by PCR-sequencing, while the PCR-RDB assay had respective rates of 98.8%, 97.1%, and 98.0%. The overall rate of HPV infection, determined by PCR-sequencing, in women diagnosed with vaginitis was 49.85%, including 36.26% of single infection and 13.6% of multiple infections. The most common infections among the 15 high-risk HPV types in women diagnosed with vaginitis were HPV-52, HPV-16, and HPV-58, with a total detection rate of 10.23%, 7.75%, and 5.85%, respectively. We conclude that the HR HPV RT PCR assay exhibits better clinical performance than the PCR-RDB assay, and is an ideal alternative method for HPV genotyping. In addition, the HR HPV RT PCR assay provides HPV DNA viral loads, and could serve as a quantitative marker in the diagnosis and treatment of single and multiple HPV infections. © 2017 Wiley Periodicals, Inc.

  1. Looking beyond human papillomavirus (HPV) genotype 16 and 18: Defining HPV genotype distribution in cervical cancers in Australia prior to vaccination.

    Science.gov (United States)

    Brotherton, Julia M L; Tabrizi, Sepehr N; Phillips, Samuel; Pyman, Jan; Cornall, Alyssa M; Lambie, Neil; Anderson, Lyndal; Cummings, Margaret; Payton, Diane; Scurry, James P; Newman, Marsali; Sharma, Raghwa; Saville, Marion; Garland, Suzanne M

    2017-10-15

    Australia has implemented a high-coverage HPV vaccination program but has not, to date, established the distribution of HPV types that occur in cervical cancers in Australia. This information is important for determining the potential for cervical cancer prevention with both current and broader spectrum HPV vaccines. We analysed 847 cervical cancers diagnosed 2005 to 2015 in tertiary centres in the three most populous Australian states with resolution of specimens containing multiple HPV types using laser-capture microdissection. Archived FFPE tissue was reviewed by specialist pathologists, sandwich sectioned, and initially whole-tissue sections genotyped for HPV. Samples were first genotyped using SPF10-LiPA25 (version 1). Negative samples were screened with DNA ELISA kit HPV SPF10, followed by genotyping with SPF+ LiPA if ELISA positive. If still negative, samples were tested on a qPCR assay targeting the E6 region of HPV16, 18, 45 and 33. Of the 847 cancers (65.1% squamous, 28.7% adenocarcinoma, 4.3% adenosquamous, 2.0% other), 92.9% had HPV detected. Of the HPV-positive cancers, 607 of 787 (77.1%) contained HPV16 or 18, 125 of 787 (15.9%) contained HPV31/33/45/52 or 58, and 55 (7.0%) another HPV type. There was a strong correlation between HPV type and age, with younger women most likely to have HPV16/18 detected and least likely HPV negative. Our findings indicate that cervical cancers diagnosed in Australia more frequently contain HPV16/18 than in international series. This could be due to cervical screening in Australia increasing the proportion of adenocarcinomas, in which types 18 and 16 more strongly predominate, due to prevention of squamous cancers. © 2017 UICC.

  2. A randomized controlled trial of Human Papillomavirus (HPV testing for cervical cancer screening: trial design and preliminary results (HPV FOCAL Trial

    Directory of Open Access Journals (Sweden)

    Smith Laurie W

    2010-03-01

    Full Text Available Abstract Background In the HPV FOCAL trial, we will establish the efficacy of hr-HPV DNA testing as a stand-alone screening test followed by liquid based cytology (LBC triage of hr-HPV-positive women compared to LBC followed by hr-HPV triage with ≥ CIN3 as the outcome. Methods/Design HPV-FOCAL is a randomized, controlled, three-armed study over a four year period conducted in British Columbia. It will recruit 33,000 women aged 25-65 through the province's population based cervical cancer screening program. Control arm: LBC at entry and two years, and combined LBC and hr-HPV at four years among those with initial negative results and hr-HPV triage of ASCUS cases; Two Year Safety Check arm: hr-HPV at entry and LBC at two years in those with initial negative results with LBC triage of hr-HPV positives; Four Year Intervention Arm: hr-HPV at entry and combined hr-HPV and LBC at four years among those with initial negative results with LBC triage of hr-HPV positive cases Discussion To date, 6150 participants have a completed sample and epidemiologic questionnaire. Of the 2019 women enrolled in the control arm, 1908 (94.5% were cytology negative. Women aged 25-29 had the highest rates of HSIL (1.4%. In the safety arm 92.2% of women were hr-HPV negative, with the highest rate of hr-HPV positivity found in 25-29 year old women (23.5%. Similar results were obtained in the intervention arm HPV FOCAL is the first randomized trial in North America to examine hr-HPV testing as the primary screen for cervical cancer within a population-based cervical cancer screening program. Trial Registration International Standard Randomised Controlled Trial Number Register, ISRCTN79347302

  3. The prevalence of "high-risk" HPV types in penile condyloma-like lesions: correlation between HPV type and morphology.

    Science.gov (United States)

    Löwhagen, G B; Bolmstedt, A; Ryd, W; Voog, E

    1993-04-01

    To evaluate the prevalence of "high-risk" human papilloma virus (HPV) types in penile condyloma-like lesions and to correlate HPV types with clinical and histological features. The study included 94 male patients with signs of penile HPV infection. From acuminate, papular and macular lesions, specimens were collected for HPV DNA hybridisation, using the dot blot and Southern blot techniques. Biopsy specimens from 51 cases were examined by light microscopy for signs of koilocytosis and dysplasia. The STD outpatient clinic of the Department of Dermatovenereology of Sahlgrenska Hospital, Göteborg, Sweden. In 79 (90%) of 88 patients HPV DNA was detected by dot blot. Of 51 cases examined by histology 88% disclosed an evident koilocytosis. "High-risk" HPV types (16, 18, 31, 33, 35) were demonstrated in 8% of acuminate, 24% of papular and 56% of macular lesions. In 29% of 51 lesions examined histologically moderate to severe dysplasia was observed. There was a significant correlation between "high-risk" HPV types and dysplasia. "High-risk" HPV types are prevalent in papular and especially macular penile condyloma-like lesions. The histological finding of koilocytosis concomitant with dysplasia strongly indicates infection with a "high-risk" HPV type. Although the risk of penile cancer is low, it is from an epidemiological point of view important to diagnose these lesions. Until simple tests for HPV typing are available, biopsy for light microscopy (histology) should be obtained liberally from papular and macular condyloma-like lesions. In atypical cases of balanoposthitis HPV aetiology should also be considered.

  4. Impact of an HPV6/11/16/18 L1 virus-like particle vaccine on progression to cervical intraepithelial neoplasia in seropositive women with HPV16/18 infection

    DEFF Research Database (Denmark)

    Haupt, Richard M; Wheeler, Cosette M; Brown, Darron R

    2011-01-01

    prevaccination. Incidence is expressed as the number of women with an endpoint per 100 person-years-at-risk. In total, 419 vaccine and 446 placebo recipients were both seropositive and DNA positive to HPV16 or HPV18 prevaccination and had at least one follow-up visit. In Protocol 013, the incidence of HPV16...

  5. Extracellular DNA as an essential component and therapeutic target of microbial biofilm

    OpenAIRE

    Urszula Wnorowska; Marzena Wątek; Bonita Durnaś; Katarzyna Głuszek; Ewelina Piktel; Katarzyna Niemirowicz; Robert Bucki

    2015-01-01

    The dominant part of human infections is associated with biofilm formations. Biofilm represents structured communities of bacterial or fungal cells enclosed in self-produced polymeric matrixes adherent to supporting surfaces. Microbial DNA and the host cell DNA, after their release at the infection site, show the ability to promote biofilm formation. Between the different constituents of biofilm matrixes, extracellular DNA (eDNA) may be the only component indispensable for the initial attachm...

  6. Carcinogenic HPV infection in the cervical squamo-columnar junction.

    Science.gov (United States)

    Mirkovic, Jelena; Howitt, Brooke E; Roncarati, Patrick; Demoulin, Stephanie; Suarez-Carmona, Meggy; Hubert, Pascale; McKeon, Frank D; Xian, Wa; Li, Anita; Delvenne, Philippe; Crum, Christopher P; Herfs, Michael

    2015-07-01

    Recent studies have suggested the involvement of a unique population of cells at the cervical squamo-columnar junction (SCJ) in the pathogenesis of early (squamous intraepithelial lesion or SIL) and advanced (squamous cell and adeno-carcinomas) cervical neoplasia. However, there is little evidence to date showing that SCJ cells harbour carcinogenic HPV or are instrumental in the initial phases of neoplasia. This study was designed to (1) determine if normal-appearing SCJ cells contained evidence of carcinogenic HPV infection and (2) trace their transition to early SIL. Sections of cervix from high-risk reproductive age women were selected and SCJ cells were analysed by using several techniques which increasingly implicated HPV infection: HPV DNA (genotyping and in situ hybridization)/RNA (PCR), immunostaining for HPV16 E2 (an early marker of HPV infection), p16(ink4), Ki67, and HPV L1 protein. In 22 cases with a history of SIL and no evidence of preneoplastic lesion in the excision specimen, HPV DNA was isolated from eight of ten with visible SCJ cells, six of which were HPV16/18 DNA-positive. In five of these latter cases, the SCJ cells were positive for p16(ink4) and/or HPV E2. Transcriptionally active HPV infection (E6/E7 mRNAs) was also detected in microdissected SCJ cells. Early squamous atypia associated with the SCJ cells demonstrated in addition diffuse p16(ink4) immunoreactivity, elevated proliferative index, and rare L1 antigen positivity. We present for the first time direct evidence that normal-appearing SCJ cells can be infected by carcinogenic HPV. They initially express HPV E2 and their progression to SIL is heralded by an expanding metaplastic progeny with increased proliferation and p16(ink4) expression. Whether certain SCJs are more vulnerable than others to carcinogenic HPV genotypes and what variables determine transition to high-grade SIL remain unresolved, but the common event appears to be a vulnerable cell at the SCJ. Copyright © 2015

  7. US assessment of HPV types in cancers: implications for current and 9-valent HPV vaccines.

    Science.gov (United States)

    Saraiya, Mona; Unger, Elizabeth R; Thompson, Trevor D; Lynch, Charles F; Hernandez, Brenda Y; Lyu, Christopher W; Steinau, Martin; Watson, Meg; Wilkinson, Edward J; Hopenhayn, Claudia; Copeland, Glenn; Cozen, Wendy; Peters, Edward S; Huang, Youjie; Saber, Maria Sibug; Altekruse, Sean; Goodman, Marc T

    2015-06-01

    This study sought to determine the prevaccine type-specific prevalence of human papillomavirus (HPV)-associated cancers in the United States to evaluate the potential impact of the HPV types in the current and newly approved 9-valent HPV vaccines. The Centers for Disease Control and Prevention partnered with seven US population-based cancer registries to obtain archival tissue for cancers diagnosed from 1993 to 2005. HPV testing was performed on 2670 case patients that were fairly representative of all participating cancer registry cases by age and sex. Demographic and clinical data were evaluated by anatomic site and HPV status. Current US cancer registry data and the detection of HPV types were used to estimate the number of cancers potentially preventable through vaccination. HPV DNA was detected in 90.6% of cervical, 91.1% of anal, 75.0% of vaginal, 70.1% of oropharyngeal, 68.8% of vulvar, 63.3% of penile, 32.0% of oral cavity, and 20.9% of laryngeal cancers, as well as in 98.8% of cervical cancer in situ (CCIS). A vaccine targeting HPV 16/18 potentially prevents the majority of invasive cervical (66.2%), anal (79.4%), oropharyngeal (60.2%), and vaginal (55.1%) cancers, as well as many penile (47.9%), vulvar (48.6%) cancers: 24 858 cases annually. The 9-valent vaccine also targeting HPV 31/33/45/52/58 may prevent an additional 4.2% to 18.3% of cancers: 3944 cases annually. For most cancers, younger age at diagnosis was associated with higher HPV 16/18 prevalence. With the exception of oropharyngeal cancers and CCIS, HPV 16/18 prevalence was similar across racial/ethnic groups. In the United States, current vaccines will reduce most HPV-associated cancers; a smaller additional reduction would be contributed by the new 9-valent vaccine. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  8. Hepatitis B surface antigen fusions delivered by DNA vaccination elicit CTL responses to human papillomavirus oncoproteins associated with tumor protection.

    Science.gov (United States)

    Haigh, O; Kattenbelt, J; Cochrane, M; Thomson, S; Gould, A; Tindle, R

    2010-10-01

    We describe the construction and evaluation of a recombinant hepatitis B surface antigen (HBsAg)-vectored DNA vaccine encoding the E7 and E6 tumor-associated oncoproteins of human papillomavirus (HPV) type 16. We show the induction of effector and memory cytotoxic T lymphocyte responses to E7 and E6 class I-restricted epitopes after a single immunization, which were associated with tumor prevention and therapy. The findings vindicate the use of a HBsAg-based DNA vaccine as a vehicle to elicit responses to co-encoded tumor antigens, and have specific implications for the development of a therapeutic vaccine for HPV-associated squamous carcinomas.

  9. Constitutive activation of the DNA damage response pathway as a novel therapeutic target in diffuse large B-cell lymphoma

    Science.gov (United States)

    Derenzini, Enrico; Agostinelli, Claudio; Imbrogno, Enrica; Iacobucci, Ilaria; Casadei, Beatrice; Brighenti, Elisa; Righi, Simona; Fuligni, Fabio; Di Rorà, Andrea Ghelli Luserna; Ferrari, Anna; Martinelli, Giovanni; Pileri, Stefano; Zinzani, Pier Luigi

    2015-01-01

    The recent finding that MYC-driven cancers are sensitive to inhibition of the DNA damage response (DDR) pathway, prompted us to investigate the role of DDR pathway as therapeutic target in diffuse large B-cell lymphoma (DLBCL), which frequently overexpresses the MYC oncogene. In a preliminary immunohistochemical study conducted on 99 consecutive DLBCL patients, we found that about half of DLBCLs showed constitutive expression of the phosphorylated forms of checkpoint kinases (CHK) and CDC25c, markers of DDR activation, and of phosphorylated histone H2AX (γH2AX), marker of DNA damage and genomic instability. Constitutive γH2AX expression correlated with c-MYC levels and DDR activation, and defined a subset of tumors characterised by poor outcome. Next, we used the CHK inhibitor PF-0477736 as a tool to investigate whether the inhibition of the DDR pathway might represent a novel therapeutic approach in DLBCL. Submicromolar concentrations of PF-0477736 hindered proliferation in DLBCL cell lines with activated DDR pathway. These results were fully recapitulated with a different CHK inhibitor (AZD-7762). Inhibition of checkpoint kinases induced rapid DNA damage accumulation and apoptosis in DLBCL cell lines and primary cells. These data suggest that pharmacologic inhibition of DDR through targeting of CHK kinases may represent a novel therapeutic strategy in DLBCL. PMID:25544753

  10. Detection of HPV and the role of p16INK4A overexpression as a surrogate marker for the presence of functional HPV oncoprotein E7 in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Lardon Filip

    2010-03-01

    Full Text Available Abstract Background Based on the well-recognized etiological role of human papillomavirus (HPV in cervical, anogenital and oropharyngeal carcinogenesis, a potential role of HPV in colorectal carcinogenesis has been suggested. For that reason, the aim of the present study was to investigate the presence of HPV DNA in colorectal carcinomas (CRC and to study overexpression of p16INK4A as a marker for the presence of an active HPV oncoprotein E7. These findings were correlated with clinical and pathological prognostic factors of CRC. Methods The presence of HPV was assessed using a multiplex PCR system of 10 non-biotinylated primers. The amplified fragments of HPV positive samples were further analyzed by a highly sensitive, broad spectrum SPF10 PCR and subsequently genotyped using reverse hybridization in a line probe assay. P16INK4A protein expression was investigated in a subset of 90 (30 HPV positive and 60 HPV negative CRC samples by immunohistochemistry. Results HPV DNA was found in 14.2% of the CRC samples with HPV16 as the most prevalent type. No significant differences in clinical and pathological variables were found between HPV positive and negative CRCs, except for age. HPV positive patients were significantly younger (p = 0.05. There was no significant correlation between the presence of HPV and overexpression of p16INK4A (p = 0.325. Conclusions In conclusion, the presence of oncogenic HPV DNA in a small cohort of CRC samples may suggest that HPV may be involved in the carcinogenesis of some CRC. However, contrary to what has been observed in head and neck squamous cell cancer and cancer of the uterine cervix, p16INK4A does not seem to be a surrogate marker for an active HPV infection in CRC. Therefore, further functional analyses are necessary to elucidate the role of HPV in CRC.

  11. Therapeutic silencing of HPV 16 E7 by systemic administration of siRNA-neutral DOPC nanoliposome in a murine cervical cancer model with obesity.

    Science.gov (United States)

    Chapoy-Villanueva, Hector; Martinez-Carlin, Ivonne; Lopez-Berestein, G; Chavez-Reyes, Arturo

    2015-01-01

    To evaluate the effectiveness of a neutral DOPC nanoliposome system for the delivery of siRNA to tumor cells in an obese murine cervical cancer model. In vitro silencing of E6-E7 mRNA and E7 protein using siRNAE6 or siRNAE7 was analyzed in TC-1 cells by RT-PCR and Western blot. Silencing and antitumor capacities of siRNAE7-DOPC-nanoparticles (NP) were tested in vivo in both normal and obese mice using qPCR. These NPs were administered twice a week for 15 days and tumor volume and weight were recorded. Levels of in vitro E6-E7 silencing were 90% for mRNA and 60% for protein when siRNAE7 was used. On the other hand when siRNAE6 was used, the levels of silencing were 50% for E6-E7 mRNA and only 20% for protein. In vivo E7 mRNA silencing by siRNAE7-DOPC-NP was similar (60%) in both non-obese and obese mouse models. The therapeutic study showed a 65% decrease in tumor volume and a 57% reduction in tumor weight as compared to the control groups. There was no negative impact of obesity on the antitumor activity of siRNA-DOPC-NP in obese mice.

  12. Extracellular DNA as an essential component and therapeutic target of microbial biofilm

    Directory of Open Access Journals (Sweden)

    Urszula Wnorowska

    2015-07-01

    Full Text Available The dominant part of human infections is associated with biofilm formations. Biofilm represents structured communities of bacterial or fungal cells enclosed in self-produced polymeric matrixes adherent to supporting surfaces. Microbial DNA and the host cell DNA, after their release at the infection site, show the ability to promote biofilm formation. Between the different constituents of biofilm matrixes, extracellular DNA (eDNA may be the only component indispensable for the initial attachment and early biofilm formation through an enhanced matrix structural integrity. The effect of DNA on bacterial/fungal attachment is non-specific, as indicated by the stimulatory effect of plasmid, chromosome, or eukaryotic DNA. DNase I impaired bacterial biofilm growth and the targeting eDNA were recently proposed to eliminate and/or prevent different microbial infections associated with biofilm formations.

  13. Diversity of HPV types in cancerous and pre-cancerous penile lesions of South African men: implications for future HPV vaccination strategies.

    Science.gov (United States)

    Lebelo, Ramokone L; Boulet, Gaëlle; Nkosi, Cornelius M; Bida, Mechack N; Bogers, John-Paul; Mphahlele, M Jeffrey

    2014-02-01

    This study reports the detection of HPV types from cancerous and pre-cancerous penile lesions that were diagnosed histologically. Sixty-six (22 pre-cancerous and 44 cancerous lesions) tissue biopsies, received between 2004 and 2011 by the Anatomical Pathology Department at Dr. George Mukhari Hospital were selected for this study. Total DNA was extracted and genotyped using type specific real-time quantitative polymerase chain reaction (qPCR) for 18 HPV types. Of 66 samples, only 51 were included in the analysis. Overall, HPV 11 (50.9%) and HPV 16 (49.1%) showed almost similar incidence in the study patients. In pre-cancerous lesions, HPV 11 was more frequent (80.0%), followed by HPV 31 and HPV 16 at 25.0% each and other HPV types included 35 (15.0%), 59 (15.0%), 53 (10.0%), 33 (10.0%), 18 (5.0%), 51 (5.0%), 52 (5.0%), 56 (5.0%), and 67 (5.0%). For cancerous lesions, HPV 16 was the most detected (62.9%), followed by HPV 11 (34.3%), and other HPV types included 18 (11.4%), 33 (5.7%), 39 (5.7%), 45 (5.7%), 66 (5.7%), 52 (2.9%), 58 (2.9%), 6 (2.9%), and 67 (2.9%). Several lesions demonstrated multiple HPV infections, ranging from two to six different types in one lesion. The study showed high diversity of HPV types in cancerous and pre-cancerous lesions of South African males with the most frequent being HPV types 11 and 16. The data suggest that boys could directly benefit from vaccination as they are exposed to variety of HPV types as early as 10 years of age in Africa. © 2013 Wiley Periodicals, Inc.

  14. HPV in HIV-Infected Women: Implications for Primary Prevention

    Science.gov (United States)

    McKenzie, Nathalie Dauphin; Kobetz, Erin N.; Ganjei-Azar, Parvin; Rosa-Cunha, Isabella; Potter, JoNell E.; Morishita, Atsushi; Lucci, Joseph A.; Guettouche, Toumy; Hnatyszyn, James H.; Koru-Sengul, Tulay

    2014-01-01

    Background: There is growing evidence that human immunodeficiency virus (HIV)-infected women might have a different human papillomavirus (HPV) type distribution in cervical dysplasia specimens as compared to the general population. This has implications for primary prevention. Objective: We aimed to obtain preliminary data on the HPV genotypes prevalent in histological samples of HIV-infected women with cervical intraepithelial neoplasia (CIN) 3/CIS of the cervix in Miami, FL, USA. Methods: Retrospective data were collected on HIV-infected women referred to the University of Miami-Jackson Memorial Hospital colposcopy clinic between years 2000 and 2008. The histology slides of CIN 3/CIS biopsies underwent pathological review and sections were cut from these archived specimens for HPV DNA extraction. HPV genotyping was then performed using the GeneSquare™ HPV genotyping assay. We report on our first set of 23 samples. Results: Eight high-risk HPV types were detected. Types in decreasing order of frequency were 16, 35, 45, 52, 59, 31, 58, and 56. Most cases had multiple infections. HPV type 16 was the most common (45%) followed by HPV-35 and -45 with equal frequency (40%). No samples contained HPV-18. Conclusion: Our preliminary results suggest that cervical dysplasia specimens of HIV-infected women more likely (55%) contain non-16 and -18 high-risk HPV types. We show that this held true for histologically confirmed severe dysplasia and carcinoma-in situ. Epidemiological studies guide vaccine development, therefore HPV type prevalence in CIS and invasive cervical cancer among HIV-infected women should be more rigorously explored to ensure that this highly vulnerable population receives appropriate primary prevention. PMID:25161956

  15. Frequency of Human Papillomavirus (HPV) 16 and 18 Detection in Paraffin- Embedded Laryngeal Carcinoma Tissue

    Science.gov (United States)

    Hosseini, Seyed Zinab; Makvandi, Manoochehr; Samarbafzade, Alireza; Timori, Ali; Ranjbar, Nastaran; Saki, Nader; Nisi, Nilofar; Shahani, Toran; Varnaseri, Mehran; Ahmadi, Kambiz Angali

    2017-01-01

    Background and Objective: Human papilloma virus (HPV) 16 and HPV18 have been detected in head and neck squamous cell carcinomas (HNSCC) and there is evidence that detection of HPVs would have better prognostic value than patients with HNSCC negative for HPVs. Thus, this study was conducted to evaluate frequency of HPV 16 and HPV 18 genotypes in patients with laryngeal carcinoma. Materials and methods: Fifty formalin-fixed, paraffin-embedded (FFPE) tissue blocks of laryngeal cancers were collected. Sections were prepared at 5 µm and DNA was extracted from each sample and subjected to the polymerase chain reaction (PCR) to detect HPV-16/18 DNA s. Results: All samples were squamous cell carcinomas (SCCs). Overall 14/50 (28%) were positive for HPVs, 8 (18%) with HPV-16 and 6 (12%) with HPV-18. Additionally, 2 (4%) mixed infections of HPV 16 and 18 genotypes were observed among these cases. Conclusions: Overall, 28% of HNSCC samples proved positive for HPV16 and HPV18 genotypes, two high-risk HPV types. It is important to further assess whether such viral infection, could be a risk factor in HNSCC progression. PMID:28545184

  16. Correlation between HPV status at T and N sites of oropharyngeal squamous cell carcinomas.

    Science.gov (United States)

    Josiassen, Michael Vallop; Charabi, Birgitte; Lajer, Christel Braemer; Garnaes, Emilie; Hamilton Therkildsen, Marianne; Norrild, Bodil; Specht, Lena; Nielsen, Finn Cilius; von Buchwald, Christian

    2017-12-01

    Human papilloma virus (HPV) is known to be associated with oropharyngeal squamous cell carcinomas (OPSCC) and may potentially play a vital role in tumor metastasis. The purpose of this study was to correlate HPV status of cervical lymph node metastases with their respective primary OPSCC tumor. Formalin-fixed, paraffin-embedded (FFPE) tissue samples obtained from 34 patients with cervical lymph node metastases were analyzed with HPV 16 DNA polymerase chain reaction (PCR), p16 immunohistochemistry and HPV typing. The results were correlated with the HPV status and type found in the primary tumors of OPSCC. Comparing HPV DNA status with p16 we found that 21 primary tumors and lymph node metastases were HPV positive (61.8%) and seven primary tumors and lymph node metastases were HPV negative (20.6%). Six patient samples differed when correlating the primary tumor and lymph node metastasis (17.6%). In this study, HPV status in OPSCCs and their cervical lymph node metastases correlated in the vast majority of cases. However, HPV detection methods may have certain limitations resulting in varying degree of non-correlation. This should be taken into account when stratifying treatment in regard to HPV status.

  17. Prevalence of human papillomavirus in saliva of women with HPV genital lesions.

    Science.gov (United States)

    Visalli, Giuseppa; Currò, Monica; Facciolà, Alessio; Riso, Romana; Mondello, Placido; Laganà, Pasqualina; Di Pietro, Angela; Picerno, Isa; Spataro, Pasquale

    2016-01-01

    The human papilloma viruses (HPVs) are DNA viruses associated with benign and malignant lesions of skin and mucous membranes. The HPVs has been implicated as the cause of virtually all cervical cancers worldwide but studies showed that these viruses can cause numerous cancers in several tissues including Oral Squamous Cell Carcinoma (OSCC). At least 90 % of HPV-positive OSCCs are associated with high-risk (or oncogenic) HPV-16 and oral infection confers an approximate 50-fold increase in risk for HPV-positive OSCC. HPV-positive OSCCs are associated with sexual behaviors in contrast to HPV-negative OSCCs that are associated with chronic tobacco and alcohol use. The aim of this study was to estimate the prevalence of HPV-DNA in saliva samples collected from women in which it has been previously established the HPV infection of the cervix with relative genotyping and, then, to study the possible correlation. Saliva samples were collected from 100 women with HPV cervical lesions, aged between 22 and 52 years old, and 25 healthy women with normal cytology (control group), aged between 20 and 49 years old. PCR assay was used to detect HPV DNA. The prevalence of oral HPV infection in saliva samples was 24 % in women with HPV cervical lesions while in the control group was 8 %. It has been demonstrated a strong association between high grade squamous intraepithelial lesion and oral infection due to HPV16 and 18, that are the most frequently detected HPV genotypes. This study shows that patients with genital HPV infection are at risk for oral infection and, consequently, for the development of OSCC.

  18. Gene expression profiles in HPV-infected head and neck cancer.

    Science.gov (United States)

    Schlecht, N F; Burk, R D; Adrien, L; Dunne, A; Kawachi, N; Sarta, C; Chen, Q; Brandwein-Gensler, M; Prystowsky, M B; Childs, G; Smith, R V; Belbin, T J

    2007-11-01

    Epidemiological and laboratory evidence indicate that, in addition to tobacco and alcohol, human papillomaviruses (HPV) play an important aetiological role in a subset of head and neck squamous cell carcinoma (HNSCC). To evaluate the molecular pathogenesis of HPV-infected HNSCC, we compared gene expression patterns between HPV-positive and -negative HNSCC tumours using cDNA microarrays. Tumour tissue was collected from 42 histologically confirmed HNSCC patients from an inner-city area of New York. Total DNA and RNA were extracted and purified from frozen tumour samples and gene expression levels were compared to a universal human reference RNA standard using a 27 323 cDNA microarray chip. HPV detection and genotyping were performed using an MY09/11-PCR system and RT-PCR. HPV was detected in 29% of HNSCC tumours. Most harboured only HPV16 and expressed the HPV16-E6 oncogene. HPV prevalence was highest in pharyngeal tumours (45%). Gene expression patterns that differentiated HPV-positive from negative tumours were compared by supervised classification analysis, and a multiple-gene signature was found to predict HPV16 prevalence in primary HNSCC with a false discovery rate HPV16-positive HNSCC. Overexpressed genes in HPV-positive HNSCC tumours included the retinoblastoma-binding protein (p18), replication factor-C gene, and an E2F-dimerization partner transcription factor (TFDP2) that have also been found to be overexpressed in cervical cancer. An additional subset of genes involved in viral defence and immune response, including interleukins and interferon-induced proteins, was found to be down-regulated in HPV-positive tumours, supporting a characteristic and unique transcriptional profile in HPV-induced HNSCC. Copyright 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  19. Application of molecular genotyping to determine prevalence of HPV strains in Pap smears of Kazakhstan women.

    Science.gov (United States)

    Niyazmetova, Luiza; Aimagambetova, Gulzhanat; Stambekova, Nazigul; Abugalieva, Zaurech; Seksembayeva, Korlukain; Ali, Syed; Azizan, Azliyati

    2017-01-01

    Human papillomavirus is the main causative agent for cervical cancer. However, few data are available about HPV prevalence in Kazakhstan. The aims of this study were to genotype HPV DNA in Pap smear samples of women to determine prevalence of carcinogenic HPV types in Astana, Kazakhstan and to analyze the association between HPV positivity and the cytology results of patient samples. Pap smear materials were obtained from 140 patients aged 18-59, who visited the outpatient gynecological clinic. Microscopic examination was done to detect dysplasia, and HPV genotyping was done using real-time multiplex PCR. HPV testing showed that among 61 HPV positive patients, the most prevalent types were 16 and 18. Microscopic examination showed that 79% of the samples had normal cytology, while 13% had CIN grade I, 5% had CIN grade II, and 3% had CIN grade III. The analysis revealed that 12% of the samples had CIN cytology and presence of HPV. Approximately 31% had HPV without cervical dysplasia, while 8% of samples were CIN positive without HPV infection. A statistically significant relationship between HPV 16 and HPV 33 positive samples and CIN grade II and III was found. Overall, this study will help to strengthen and guide health policy implementation of primary and secondary cervical cancer prevention strategies in Kazakhstan. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  20. HPV-specific immunotherapy: key role for immunomodulators.

    Science.gov (United States)

    Van de Wall, Stephanie; Nijman, Hans W; Daemen, Toos

    2014-02-01

    Cervical cancer is the second most common malignancy among women worldwide. The prime causal factor of the disease is a persistent infection with human papillomavirus (HPV) with individuals failing to mount a sufficient immune response against the virus. Despite the current success of HPV16- and 18-specific prophylactic vaccination, established HPV infections and associated neoplasia require therapeutic vaccines with the induction of cellular immunity. The sustained expression of early proteins E6 and E7 from major oncogenic HPV genotypes in cervical lesions are ideal targets for the design of immunotherapeutic strategies. These strategies, particularly subunit vaccines, may require additional help from immunomodulators to enhance HPV-specific cellular responses. This review discusses recent studies, published since 2008, relating to immunotherapeutic strategies against HPV that include immunomodulators. These immunomodulators fall within the category of toll-like receptor adjuvants for innate immune activation, adjuvants directly contributing to adaptive immunity, such as cytokines and costimulatory molecules, and those that target tumor-induced immunosuppressive mechanisms. Using a combination of these strategies with delivery-based approaches may be most beneficial for the success of therapeutic vaccines against HPV-induced neoplasia in the clinic.

  1. Genetic Diversity in the Major Capsid L1 Protein of HPV-16 and HPV-18 in the Netherlands.

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    Audrey J King

    Full Text Available Intratypic molecular variants of human papillomavirus (HPV type-16 and -18 exist. In the Netherlands, a bivalent vaccine, composed of recombinant L1 proteins from HPV-16 and -18, is used to prevent cervical cancer since 2009. Long-term vaccination could lead to changes in HPV-16 and -18 virus population, thereby hampering vaccination strategies. We determined the genetic diversity of the L1 gene in HPV-16 and -18 viral strains circulating in the Netherlands at the start of vaccination in order to understand the baseline genetic diversity in the Dutch population.DNA sequences of the L1 gene were determined in HPV-16 (n = 241 and HPV-18 (n = 108 positive anogenital samples collected in 2009 and 2011 among Dutch 16- to 24-year old female and male attendees of the sexually transmitted infection (STI clinics. Phylogenetic analysis was performed and sequences were compared to reference sequences HPV-16 (AF536179 and HPV-18 (X05015 using BioNumerics 7.1.For HPV-16, ninety-five single nucleotide polymorphism (SNPs were identified, twenty-seven (28% were non-synonymous variations. For HPV-18, seventy-one SNPs were identified, twenty-nine (41% were non-synonymous. The majority of the non-silent variations were located in sequences encoding alpha helix, beta sheet or surface loops, in particular in the immunodominant FG loop, and may influence the protein secondary structure and immune recognition.This study provides unique pre-vaccination/baseline data on the genetic L1 diversity of HPV-16 and -18 viruses circulating in the Netherlands among adolescents and young adults.

  2. Immunotherapy in new pre-clinical models of HPV-associated oral cancers.

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    Paolini, Francesca; Massa, Silvia; Manni, Isabella; Franconi, Rosella; Venuti, Aldo

    2013-03-01

    Cervical, anal, penile and a sub-set of head and neck (HN) tumors are critical health problems caused by high risk Human Papilloma Viruses (HPVs), like HPV type 16. No specific/effective pharmacological treatments exist. A valid preventive vaccination as well as the immunotherapy of persistent infections, pre-cancerous lesions or early-stage cancers could drive the HPV disease burden down. These treatments might be featured through low-cost platforms like those based on DNA and plant biotechnologies to produce tailored and enhanced formulations taking profit from the use of plants as bio-factories and as a source of immune-stimulators. Finally, and regardless of the formulation type, pre-clinical tests and models are crucial to foresee efficacy of immunotherapy before clinical trials.   In this study, we created an orthotopic mouse model for HPV-related oral tumors, a subset of HN tumors for which no models have been generated before. The model was obtained by inducing the stable expression of the HPV16 E7 protein into the mouse oral squamous cell carcinoma (OSCC) AT-84 (AT-84 E7). The AT-84 E7 cells were injected into the mouth pavement of C3H mice via an extra-oral route to obtain orthotopic tumors. The model turned out to mimic the natural history of the human HPV oral cancer. From AT-84 E7, through engineering to express luciferase, the bioluminescent AT-84 E7-Luc cells were obtained for a fast and easy monitoring by imaging. The AT-84 E7 and the AT-84 E7-Luc tumors were used to test the efficacy of E7-based therapeutic vaccines that we had previously generated and that had been already proven to be active in mice against non-orthotopic E7-expressing tumors (TC-1 cells). In particular, we used genetic and plant-derived formulations based on attenuated HPV16 E7 variants either fused to plant virus genes with immunological activity or produced by tobacco plants. Mice were monitored by imaging allowing to test the size reduction of the mouth implanted

  3. Comparison of the immunogenicity of the human papillomavirus (HPV)-16/18 vaccine and the HPV-6/11/16/18 vaccine for oncogenic non-vaccine types HPV-31 and HPV-45 in healthy women aged 18-45 years.

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    Einstein, Mark H; Baron, Mira; Levin, Myron J; Chatterjee, Archana; Fox, Bradley; Scholar, Sofia; Rosen, Jeffrey; Chakhtoura, Nahida; Lebacq, Marie; van der Most, Robbert; Moris, Philippe; Giannini, Sandra L; Schuind, Anne; Datta, Sanjoy K; Descamps, Dominique

    2011-12-01

    Protection against oncogenic non-vaccine types (cross-protection) offered by human papillomavirus (HPV) vaccines may provide a significant medical benefit. Available clinical efficacy data suggest the two licensed vaccines (HPV-16/18 vaccine, GlaxoSmithKline Biologicals (GSK), and HPV-6/11/16/18 vaccine, Merck & Co., Inc.) differ in terms of protection against oncogenic non-vaccine HPV types -31/45. The immune responses induced by the two vaccines against these two non-vaccine HPV types (cross-reactivity) was compared in an observer-blind study up to Month 24 (18 mo post-vaccination), in women HPV DNA-negative and seronegative prior to vaccination for the HPV type analyzed (HPV-010 [NCT00423046]). Geometric mean antibody titers (GMTs) measured by pseudovirion-based neutralization assay (PBNA) and enzyme-linked immunosorbent assay (ELISA) were similar between vaccines for HPV-31/45. Seropositivity rates for HPV-31 were also similar between vaccines; however, there was a trend for higher seropositivity with the HPV-16/18 vaccine (13.0-16.7%) versus the HPV-6/11/16/18 vaccine (0.0-5.0%) for HPV-45 with PBNA, but not ELISA. HPV-31/45 cross-reactive memory B-cell responses were comparable between vaccines. Circulating antigen-specific CD4+ T-cell frequencies were higher for the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (HPV-31 [geometric mean ratio [GMR] =2.0; p=0.0002] and HPV-45 [GMR=2.6; p=0.0092]), as were the proportion of T-cell responders (HPV-31, p=0.0009; HPV-45, p=0.0793). In conclusion, immune response to oncogenic non-vaccine HPV types -31/45 was generally similar for both vaccines with the exception of T-cell response which was higher with the HPV-16/18 vaccine. Considering the differences in cross-protective efficacy between the two vaccines, the results might provide insights into the underlying mechanism(s) of protection.

  4. Protection of mice by a λ-based therapeutic vaccine against cancer associated with human papillomavirus type 16.

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    Ghaemi, Amir; Soleimanjahi, Hoorieh; Gill, Pooria; Hassan, Zuhair M; Razeghi, Soodeh; Fazeli, Maryam; Razavinikoo, Seyed Mohammad H

    2011-01-01

    Human papillomavirus (HPV) oncoproteins (i.e. E6 and E7) are constitutively expressed in cervical cancer cells. The proteins are ideal targets to be used for developing therapeutic vaccines against existing HPV-associated carcinomas. To date, whole bacteriophage ('phage')-λ particles, rather than purified 'naked' DNA, have been described as highly efficient delivery vehicles for a DNA vaccine. In this study, a safe and efficient λ-based therapeutic cancer vaccine, recombinant λ-ZAP E7 phage, was developed by inserting a HPV16 E7 gene into the Lambda ZAP® cytomegalovirus vector. λ-ZAP E7 phages were employed to immunize mice against the E7-expressing murine tumor cell line (TC-1), which is used as a tumor model in an H-2b murine system. The tumor-bearing mice indicated a significant inhibition of tumor growth after 3 injections of 2 × 10(12) particles of recombinant phages. Released lactate dehydrogenase, interferon-γ and granzyme B from spleen cells and lymphocyte proliferation of spleen cells, which all demonstrate the enhancement of cell-mediated immunity, suggested the phages could be a potent gene delivery system in animal models. Our results suggest the recombinant phages can be used as effective biological tools for inducing E7-specific protective immune responses. Hence, the study introduces a possible therapeutic strategy against cervical cancer and other HPV-related neoplasia. Copyright © 2010 S. Karger AG, Basel.

  5. DETEKSI INFEKSI Human palillomavirus (HPV 16/18 PADA KARSINOMA SEL SKUAMOSA RONGGA MULUT DENGAN NESTED PCR

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    Siti Hamidatul Aliyah

    2016-05-01

    Full Text Available ABSTRACTHead and neck cancer ranks fourth nationally cancer incidence in Indonesia. Oral SCC is one of Head and neck cancer incidence. Oral SCC related to several factors, including  smoking, alcohol, viral infection human papillomavirus (HPV 16/18 and genetic On the other hand, HPV E6 oncoprotein binds and inactivates TP53, and result in loss of control of the cell cycle. This study aimed to detect HPV 16/18 infection in oral SCC. Detection of HPV serotypes 16 and 18 performed on FFPE DNA isolates oral SCC with the method of nested Polymerase Chain Reaction (PCR. Nested PCR was performed in two stages, namely amplification with L1 primer, followed by specific PCR E6 HPV-16 and HPV-18. A total of 33% (11/33 FFPE samples showed positive for HPV 18 infection (single-sized DNA bands 415bp and not detected the presence of infection with HPV 16. It can be concluded that the type of FFPE biosampel can be used for studies related to HPV infection. Furthermore, it should be tested on different types biosampel by a larger amount so as to represent the prevalence of oncogenic HPV infection in Indonesia.Keyword: Oral SCC, HPV 16/18, PCR, FFPE ABSTRAKKanker kepala dan leher menempati urutan kejadian kanker keempat di Indonesia. KSS rongga mulut merupakan salah satu kejadian kepala dan kanker leher. KSS rongga mulut terkait dengan beberapa faktor, termasuk merokok, alkohol, infeksi virus human papillomavirus (HPV 16/18 dan genetik Di sisi lain, HPV E6 mengikat onkoprotein dan menginaktivasi TP53, dan mengakibatkan hilangnya kontrol dari siklus sel. Penelitian ini bertujuan untuk mendeteksi HPV 16/18 infeksi pada KSS rongga mulut Deteksi HPV serotipe 16 dan 18 dilakukan pada FFPE DNA isolat SCC lisan dengan metode bersarang Polymerase Chain Reaction (PCR. Nested PCR dilakukan dalam dua tahap, yaitu amplifikasi dengan L1 primer, diikuti dengan PCR spesifik E6 HPV-16 dan HPV-18. Sebanyak 33% (11/33 sampel FFPE menunjukkan hasil positif untuk HPV 18 infeksi

  6. Anal, penile, and oral high-risk HPV infections and HPV seropositivity in HIV-positive and HIV-negative men who have sex with men.

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    Vera M van Rijn

    Full Text Available The effects of single or multiple concordant HPV infections at various anatomical sites on type-specific HPV seropositivity are currently unknown. In this cross-sectional study we assessed whether high-risk HPV infections at various anatomical sites (i.e., anal canal, penile shaft, and oral cavity, as well as concordant infections at multiple anatomical sites, were associated with type-specific seropositivity in HIV-positive and HIV-negative MSM. MSM aged ≥ 18 years were recruited in Amsterdam, the Netherlands (2010-2011. Baseline anal, penile, and oral samples were analyzed for HPV DNA and genotyped using a highly sensitive PCR and reverse line blot assay. Virus-like particle (VLP based multiplex immunoassay was used to asses HPV-specific serum antibodies against L1 VLPs. The associations between HPV infections and type-specific seropositivity of seven high-risk HPV types (7-hrHPV: types 16, 18, 31, 33, 45, 52, 58 were estimated using logistic regression analyses with generalized estimating equations. We found that 86% of 306 HIV-positive MSM and 62% of 441 HIV-negative MSM were seropositive for at least one 7-hrHPV type. 69% of HIV-positive and 41% of HIV-negative MSM were infected with at least one 7-hrHPV type at the anus, penis, or oral cavity. In multivariable analyses, 7-hrHPV seropositivity was associated with type-specific anal (and not penile 7-hrHPV infection, and did not significantly increase with a higher number of infected anatomical sites. Oral 7-hrHPV infection showed a positive, albeit non-significant, association with seropositivity. In conclusion, seropositivity among MSM appears to be largely associated with anal HPV infection, irrespective of additionally infected anatomical sites.

  7. DNA and aptamer stabilized gold nanoparticles for targeted delivery of anticancer therapeutics

    Science.gov (United States)

    Latorre, Alfonso; Posch, Christian; Garcimartín, Yolanda; Celli, Anna; Sanlorenzo, Martina; Vujic, Igor; Ma, Jeffrey; Zekhtser, Mitchell; Rappersberger, Klemens; Ortiz-Urda, Susana; Somoza, Álvaro

    2014-06-01

    Gold nanoparticles (GNPs) can be used as carriers of a variety of therapeutics. Ideally, drugs are released in the target cells in response to cell specific intracellular triggers. In this study, GNPs are loaded with doxorubicin or AZD8055, using a self-immolative linker which facilitates the release of anticancer therapeutics in malignant cells without modifications of the active compound. An additional modification with the aptamer AS1411 further increases the selectivity of GNPs towards cancer cells. Both modifications increase targeted delivery of therapeutics with GNPs. Whereas GNPs without anticancer drugs do not affect cell viability in all cells tested, AS1411 modified GNPs loaded with doxorubicin or AZD8055 show significant and increased reduction of cell viability in breast cancer and uveal melanoma cell lines. These results highlight that modified GNPs can be functionalized to increase the efficacy of cancer therapeutics and may further reduce toxicity by increasing targeted delivery towards malignant cells.Gold nanoparticles (GNPs) can be used as carriers of a variety of therapeutics. Ideally, drugs are released in the target cells in response to cell specific intracellular triggers. In this study, GNPs are loaded with doxorubicin or AZD8055, using a self-immolative linker which facilitates the release of anticancer therapeutics in malignant cells without modifications of the active compound. An additional modification with the aptamer AS1411 further increases the selectivity of GNPs towards cancer cells. Both modifications increase targeted delivery of therapeutics with GNPs. Whereas GNPs without anticancer drugs do not affect cell viability in all cells tested, AS1411 modified GNPs loaded with doxorubicin or AZD8055 show significant and increased reduction of cell viability in breast cancer and uveal melanoma cell lines. These results highlight that modified GNPs can be functionalized to increase the efficacy of cancer therapeutics and may further

  8. Depletion of HPV16 early genes induces autophagy and senescence in a cervical carcinogenesis model, regardless of viral physical state.

    Science.gov (United States)

    Hanning, Jennifer E; Saini, Harpreet K; Murray, Matthew J; Caffarel, Maria M; van Dongen, Stijn; Ward, Dawn; Barker, Emily M; Scarpini, Cinzia G; Groves, Ian J; Stanley, Margaret A; Enright, Anton J; Pett, Mark R; Coleman, Nicholas

    2013-11-01

    In cervical carcinomas, high-risk human papillomavirus (HR-HPV) may be integrated into host chromosomes or remain extra-chromosomal (episomal). We used the W12 cervical keratinocyte model to investigate the effects of HPV16 early gene depletion on in vitro cervical carcinogenesis pathways, particularly effects shared by cells with episomal versus integrated HPV16 DNA. Importantly, we were able to study the specific cellular consequences of viral gene depletion by using short interfering RNAs known not to cause phenotypic or transcriptional off-target effects in keratinocytes. We found that while cervical neoplastic progression in vitro was characterized by dynamic changes in HPV16 transcript levels, viral early gene expression was required for cell survival at all stages of carcinogenesis, regardless of viral physical state, levels of early gene expression or histology in organotypic tissue culture. Moreover, HPV16 early gene depletion induced changes in host gene expression that were common to both episome-containing and integrant-containing cells. In particular, we observed up-regulation of autophagy genes, associated with enrichment of senescence and innate immune-response pathways, including the senescence-associated secretory phenotype (SASP). In keeping with these observations, HPV16 early gene depletion induced autophagy in both episome-containing and integrant-containing W12 cells, as evidenced by the appearance of autophagosomes, punctate expression of the autophagy marker LC3, conversion of LC3B-I to LC3B-II, and reduced levels of the autophagy substrate p62. Consistent with the reported association between autophagy and senescence pathways, HPV16 early gene depletion induced expression of the senescence marker beta-galactosidase and increased secretion of the SASP-related protein IGFBP3. Together, these data indicate that depleting HR-HPV early genes would be of potential therapeutic benefit in all cervical carcinogenesis pathways, regardless of viral

  9. Association of HPV infection and Chlamydia trachomatis seropositivity in cases of cervical neoplasia in Midwest Brazil.

    Science.gov (United States)

    da Silva Barros, Narriman Kennia; Costa, Maria Cecília; Alves, Rosane Ribeiro Figueiredo; Villa, Luísa Lina; Derchain, Sophie Françoise Mauricette; Zeferino, Luiz Carlos; Dos Santos Carneiro, Megmar Aparecida; Rabelo-Santos, Silvia Helena

    2012-07-01

    High-risk human papillomavirus (HPV) is considered the main etiological agent for cervical neoplasia. However, the presence of a single type HPV infection alone is unlikely to be sufficient to cause cervical cancer. There is epidemiologic evidence suggesting that HPV and Chlamydia trachomatis play a central role in the etiology of cervical intraepithelial neoplasia and subsequent cervical cancer. To evaluate the HPV prevalence and the seropositivity for C. trachomatis in women referred to the colposcopy clinic due to an abnormal cervical smear and to examine the effect of this association on the severity of cervical neoplasia. Following enrollment, 131 patients underwent colposcopy and biopsies when necessary. HPV DNA was detected by the polymerase chain reaction (PCR) and genotyping was performed by reverse line-blot hybridization assay. C. trachomatis seropositivity was tested by ELISA for the detection of IgG antibodies. The prevalence of HPV infection was 86.3%. Seropositivity for C. trachomatis was 26%. Thirty-one women (27.4%) were positive for C. trachomatis antibodies and HPV-DNA. The most prevalent HPV type in C. trachomatis-seropositive women were HPV 16 (51.6%) and this HPV type was present mainly in neoplasia cases. Positivity for HPV, particularly HPV types 16 and 18, and C. trachomatis seropositivity was significantly associated with a diagnosis of high grade neoplasia. Borderline significance was observed after adjustment for HPV. C. trachomatis seropositivity is associated with high grade neoplasia in women infected with HPV, mainly when the types 16 and 18 were involved. Copyright © 2012 Wiley Periodicals, Inc.

  10. Intraindividual homogeneity of (18)F-FDG PET/CT parameters in HPV-positive OPSCC.

    Science.gov (United States)

    Sharma, Shachi Jenny; Wittekindt, Claus; Knuth, Jennifer; Steiner, Dagmar; Wuerdemann, Nora; Laur, Maren; Kroll, Tobias; Wagner, Steffen; Klussmann, Jens Peter

    2017-10-01

    (18)F-FDG PET/CT is widely used in clinical oncology. Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) represents an emerging disease that differs from HPV-negative OPSCC in clinical behavior and tumour biology. In these tumours, HPV-oncogenes might lead to distinct alterations in metabolic pathways. Therefore, we compared metabolic parameters using (18)F-FDG PET/CT in HPV-positive and HPV-negative OPSCC in relation to histopathological findings. Eighty-six patients with OPSCC received pre-therapeutic (18)F-FDG PET/CT. Standardised uptake volume (SUV), total lesion glycolysis (TLG) and metabolic tumour volume (MTV) were analysed for the primary tumour. SUVmax was determined for neck lymph nodes. HPV-status was determined; overall survival rates (OS) were estimated. 32/86 patients (37.2%) had HPV-related OPSCC. Overall, PET-parameters in primary tumours of both groups did not differ significantly. Comparing early with locally advanced primary tumours, there was a significant increase in (18)F-FDG uptake in HPV-negative patients (pHPV-related OPSCC showed significantly higher SUVmax values (p=0.039) compared to HPV-negative OPSCC. Strikingly, there was a higher intraindividual homogeneity of (18)F-FDG uptake between primary and respective positive nodes in HPV-related primary OPSCC (p=0.001). SUV-max and -mean values did not correlate with OS in HPV-related OPSCC. The intraindividual homogeneity of 18F-FDG uptake in HPV-related OPSCC could reflect the more homogenously, HPV-triggered carcinogenesis compared to the mutation-driven carcinogenesis in the HPV-negative OPSCC with heterogenic (18)F-FDG uptake. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Human Papillomavirus (HPV) Vaccines

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    ... caused by persistent infection and genital warts ( 22 ). Analyses of data from women participating in a clinical ... is to contact the insurance plan or the clinic. Most private insurance plans cover HPV vaccination. The ...

  12. The HPV Vaccination Crisis

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    Following the release of a consensus statement from the NCI-Designated Cancer Centers urging HPV vaccination in the United States, Dr. Noel Brewer discusses the country’s low vaccination rates and how clinicians can help to improve them.

  13. Human Papillomavirus (HPV) Screening

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search The CDC Human Papillomavirus (HPV) Note: Javascript is disabled or is ... 6348 Email CDC-INFO U.S. Department of Health & Human Services HHS/Open USA.gov TOP

  14. Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability

    Science.gov (United States)

    Akagi, Keiko; Li, Jingfeng; Broutian, Tatevik R.; Padilla-Nash, Hesed; Xiao, Weihong; Jiang, Bo; Rocco, James W.; Teknos, Theodoros N.; Kumar, Bhavna; Wangsa, Danny; He, Dandan; Ried, Thomas; Symer, David E.; Gillison, Maura L.

    2014-01-01

    Genomic instability is a hallmark of human cancers, including the 5% caused by human papillomavirus (HPV). Here we report a striking association between HPV integration and adjacent host genomic structural variation in human cancer cell lines and primary tumors. Whole-genome sequencing revealed HPV integrants flanking and bridging extensive host genomic amplifications and rearrangements, including deletions, inversions, and chromosomal translocations. We present a model of “looping” by which HPV integrant-mediated DNA replication and recombination may result in viral–host DNA concatemers, frequently disrupting genes involved in oncogenesis and amplifying HPV oncogenes E6 and E7. Our high-resolution results shed new light on a catastrophic process, distinct from chromothripsis and other mutational processes, by which HPV directly promotes genomic instability. PMID:24201445

  15. Perceptions and Experiences of Human Papillomavirus (HPV Infection and Testing among Low-Income Mexican Women.

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    Leith León-Maldonado

    Full Text Available HPV infection causes cervical cancer, a major contributor to morbidity and mortality among low-income Mexican women. Human papillomavirus (HPV DNA testing is now a primary screening strategy in Mexico's early cervical cancer detection program (ECDP. Research on Mexican women's perceptions of HPV and testing is necessary for establishing culturally appropriate protocols and educational materials. Here, we explore perceptions about HPV and HPV-related risk factors among low-income Mexican ECDP participants.We conducted semi-structured interviews with 24 ECDP participants from two primary care health clinics in Michoacán state, Mexico. Interviews addressed women's understandings of and experiences with HPV and HPV testing. Analysis was inductive and guided by the Health Belief Model with a focus on gender.Women's confusion about HPV and HPV screening caused emotional distress. They understood HPV to be a serious disease that would always cause severe symptoms, often characterizing it as analogous to HIV or inevitably carcinogenic. Women also attributed it to men's sexual behaviors, specifically infidelity and poor hygiene. Women described both sexes' desire for sex as natural but understood men's negative practices of masculinity, like infidelity, as the causes of women's HPV infection. Some women believed dirty public bathrooms or heredity could also cause HPV transmission.These results are consistent with prior findings that geographically and economically diverse populations lack clear understandings of the nature, causes, or symptoms of HPV, even among those receiving HPV testing. Our findings also reveal that local cultural discourse relating to masculinity, along with failure to provide sufficient education to low-income and indigenous-language speaking patients, exacerbate women's negative emotions surrounding HPV testing. While negative emotions did not deter women from seeking testing, they could be ameliorated with better health

  16. The epidemiology of oral HPV infection among a multinational sample of healthy men.

    Science.gov (United States)

    Kreimer, Aimee R; Villa, Alessandro; Nyitray, Alan G; Abrahamsen, Martha; Papenfuss, Mary; Smith, Danelle; Hildesheim, Allan; Villa, Luisa L; Lazcano-Ponce, Eduardo; Giuliano, Anna R

    2011-01-01

    Oral human papillomavirus type-16 (HPV16) infection is a risk factor for oropharyngeal cancer. We examined oral HPV infection among healthy men. Oral rinse/gargle specimens and questionnaire data were collected from 1,688 healthy men aged 18 to 74 (median = 31 years), from the United States, Mexico, and Brazil. HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59, and noncarcinogenic HPV types were detected using Roche Linear Array. Oral HPV DNA was detected in 67 of 1,680 (4.0%, 95% CI = 3.1%-5.0%) β-globin-positive specimens; carcinogenic HPVs were detected in 1.3% (95% CI = 0.8%-2.0%; n = 22) and HPV16 was the most commonly detected carcinogenic HPV type (0.6%, 95% CI = 0.2%-1.1%; n = 10). The prevalence of oral HPV infection was similar by country except for HPV55, which had notably higher prevalence in Mexico (3.0%) than Brazil (0%) or the United States (0.2%). Oral HPV prevalence nonsignificantly increased over increasing age categories (P(trend) = 0.096). The strongest predictor of oral HPV was current tobacco use, which increased the odds 2.5-fold (95% CI = 1.4-4.4). Oral sexual behaviors were not associated with oral HPV infection. Oral HPV16 infection was rare in healthy men, especially at younger ages, and was positively associated with current tobacco use. Oral HPV appears to be about 10-fold less prevalent than infection at genital sites in men (4% vs. ∼40%, respectively). It remains unclear whether this reflects reduced exposure or if the oral region is more resistant to HPV infection compared with anogenital sites. ©2011 AACR.

  17. Perceptions and Experiences of Human Papillomavirus (HPV) Infection and Testing among Low-Income Mexican Women.

    Science.gov (United States)

    León-Maldonado, Leith; Wentzell, Emily; Brown, Brandon; Allen-Leigh, Betania; Torres-Ibarra, Leticia; Salmerón, Jorge; Billings, Deborah L; Thrasher, James F; Lazcano-Ponce, Eduardo

    2016-01-01

    HPV infection causes cervical cancer, a major contributor to morbidity and mortality among low-income Mexican women. Human papillomavirus (HPV) DNA testing is now a primary screening strategy in Mexico's early cervical cancer detection program (ECDP). Research on Mexican women's perceptions of HPV and testing is necessary for establishing culturally appropriate protocols and educational materials. Here, we explore perceptions about HPV and HPV-related risk factors among low-income Mexican ECDP participants. We conducted semi-structured interviews with 24 ECDP participants from two primary care health clinics in Michoacán state, Mexico. Interviews addressed women's understandings of and experiences with HPV and HPV testing. Analysis was inductive and guided by the Health Belief Model with a focus on gender. Women's confusion about HPV and HPV screening caused emotional distress. They understood HPV to be a serious disease that would always cause severe symptoms, often characterizing it as analogous to HIV or inevitably carcinogenic. Women also attributed it to men's sexual behaviors, specifically infidelity and poor hygiene. Women described both sexes' desire for sex as natural but understood men's negative practices of masculinity, like infidelity, as the causes of women's HPV infection. Some women believed dirty public bathrooms or heredity could also cause HPV transmission. These results are consistent with prior findings that geographically and economically diverse populations lack clear understandings of the nature, causes, or symptoms of HPV, even among those receiving HPV testing. Our findings also reveal that local cultural discourse relating to masculinity, along with failure to provide sufficient education to low-income and indigenous-language speaking patients, exacerbate women's negative emotions surrounding HPV testing. While negative emotions did not deter women from seeking testing, they could be ameliorated with better health education and

  18. Why Human Papillomaviruses Activate the DNA Damage Response (DDR) and How Cellular and Viral Replication Persists in the Presence of DDR Signaling.

    Science.gov (United States)

    Bristol, Molly L; Das, Dipon; Morgan, Iain M

    2017-09-21

    Human papillomaviruses (HPV) require the activation of the DNA damage response (DDR) in order to undergo a successful life cycle. This activation presents a challenge for the virus and the infected cell: how does viral and host replication proceed in the presence of a DDR that ordinarily arrests replication; and how do HPV16 infected cells retain the ability to proliferate in the presence of a DDR that ordinarily arrests the cell cycle? This raises a further question: why do HPV activate the DDR? The answers to these questions are only partially understood; a full understanding could identify novel therapeutic strategies to target HPV cancers. Here, we propose that the rapid replication of an 8 kb double stranded circular genome during infection creates aberrant DNA structures that attract and activate DDR proteins. Therefore, HPV replication in the presence of an active DDR is a necessity for a successful viral life cycle in order to resolve these DNA structures on viral genomes; without an active DDR, successful replication of the viral genome would not proceed. We discuss the essential role of TopBP1 in this process and also how viral and cellular replication proceeds in HPV infected cells in the presence of DDR signals.

  19. HPV in genital cancers (at the exception of cervical cancer) and anal cancers.

    Science.gov (United States)

    de Sanjosé, Silvia; Bruni, Laia; Alemany, Laia

    2014-12-01

    Human papillomavirus (HPV) infection has been firmly established as a central and necessary cause of invasive cervical cancer and it has been etiologically linked to other anogenital (vulva, vagina, anus and penis) and head and neck cancers, particularly oropharyngeal. Although being rare, the incidence of some of these cancers in some countries has increased in the last decades. HPV-related anogenital tumors share many risk factors with cervical cancer. The HPV aetiological contribution differs in each anatomical location reflecting differences in the natural history and viral tissue tropism. The highest prevalence of HPV DNA in cancers other than cervix has been described for anal, followed by vagina, penile and vulvar cancers. HPV16 has been described as the most common type detected in all cancer sites with different contributions being the highest in anal carcinoma (around 80% of HPV DNA positive anal cancers) and the lowest in vaginal cancers with a contribution similar to that found in cervical cancers (around 60%). Current HPV vaccines have already demonstrated their efficacy in preventing anogenital pre-neoplastic lesions caused by vaccine HPV types. HPV-based prevention tools like HPV vaccination and to a lesser extend screening (e.g. for anal cancer) can be useful measures for reducing the burden of these anogenital cancers. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  20. HPV knowledge and impact of genital warts on self esteem and sexual life in Colombian patients

    OpenAIRE

    Pi?eros, Marion; Hern?ndez-Su?rez, Gustavo; Orjuela, Liliana; Vargas, Juan Carlos; P?rez, Gonzalo

    2013-01-01

    Background Information on HPV knowledge in patients with genital warts is scarse as is the information on factors related to the impact on self-esteem and sex life among them. Methods We conducted a cross-sectional study in adult patients with a clinical diagnosis of genital warts (GW) attending a major private out-patient clinic in Bogot?, Colombia. Patients underwent biopsy for pathological diagnosis, HPV-DNA testing and completed a questionnaire assessing HPV knowledge, and the consequence...

  1. Human Papillomavirus (HPV) Detection in Cytologic Specimens: Similarities and Differences of Available Methodology.

    Science.gov (United States)

    Bihl, Michel P; Tornillo, Luigi; Kind, André B; Obermann, Ellen; Noppen, Christoph; Chaffard, Rosemarie; Wynne, Patricia; Grilli, Bruno; Foerster, Anja; Terracciano, Luigi M; Hoeller, Sylvia

    2017-03-01

    Accumulating evidence regarding the causative role of human papillomavirus (HPV) in a wide range of malignant and nonmalignant diseases highlights the importance of HPV testing. This study describes and discusses the efficacy and characteristics of 4 well-established and commercially available tests. Here, 181 cytologic specimens from cervical smears were analyzed using the HPV SIGN PQ (Diatech) and the Linear Array (Roche) method. Discrepant results were further studied with the Real Time High-Risk HPV (Abbott) method and the INNO-LiPA (Fujirebio) method. Of 181 cytologic specimens, 61 (34%) showed discrepant results. High-risk HPV was not detected in 9 cases by HPV SIGN PQ, in 16 cases by Linear Array, in 10 cases by Real Time High-Risk HPV, and in 6 cases by INNO-LiPA, respectively. Lack of DNA detection or problems in interpreting the result were seen in 9 cases with HPV SIGN PQ, 8 cases with Linear Array, 3 cases with Real Time High-Risk HPV, and 3 cases with INNO-LiPA, respectively. This study indicates that the choice of HPV detection method has a substantial influence on the HPV risk classification of tested PAP smears and clinical follow-up decisions.

  2. HPV genotypes detected in cervical cancers from Alaska Native women, 1980-2007.

    Science.gov (United States)

    Kelly, Janet J; Unger, Elizabeth R; Dunne, Eileen F; Murphy, Neil J; Tiesinga, James; Koller, Kathy R; Swango-Wilson, Amy; Philemonof, Dino; Lounmala, Xay; Markowitz, Lauri E; Steinau, Martin; Hennessy, Thomas

    2013-01-01

    Human papillomavirus (HPV) vaccine prevents cervical pre-cancers and cancers caused by HPV types 16 and 18. This study provides information on the HPV types detected in cervical cancers of Alaska Native (AN) women. Cases of invasive cervical cancer diagnosed in AN women aged 18 and above between 1980 and 2007 were identified from the Alaska Native Tumor Registry. A representative formalin-fixed, paraffin-embedded archived pathology block was retrieved and serially sectioned to allow histologic confirmation of lesion (first and last sections) and PCR testing of intervening sections. Extracted DNA was tested for HPV using Linear Array HPV Genotyping Test (Roche Diagnostics) with additional INNO-LiPA HPV Genotyping Assay (Innogenetics) testing on negative or inadequate specimens. All specimens were tested for a minimum 37 HPV types. Of 62 cervical cancer specimens evaluated, 57 (91.9%) contained one or more HPV types. Thirty-eight (61.2%) cancers contained HPV types 16 or 18, and 18 (29%) contained an oncogenic type other than type 16 or 18. Overall, almost two-thirds (61.2%) of the archived cervical cancers had detectible HPV types 16 or 18, a finding similar to studies of US women. As expected, a proportion of cancers would not be prevented by the current vaccines. HPV vaccination and cervical cancer screening are important prevention strategies for AN women.

  3. HPV genotypes detected in cervical cancers from Alaska Native women, 1980–2007

    Science.gov (United States)

    Kelly, Janet J.; Unger, Elizabeth R.; Dunne, Eileen F.; Murphy, Neil J.; Tiesinga, James; Koller, Kathy R.; Swango-Wilson, Amy; Philemonof, Dino; Lounmala, Xay; Markowitz, Lauri E.; Steinau, Martin; Hennessy, Thomas

    2013-01-01

    Background Human papillomavirus (HPV) vaccine prevents cervical pre-cancers and cancers caused by HPV types 16 and 18. This study provides information on the HPV types detected in cervical cancers of Alaska Native (AN) women. Methods Cases of invasive cervical cancer diagnosed in AN women aged 18 and above between 1980 and 2007 were identified from the Alaska Native Tumor Registry. A representative formalin-fixed, paraffin-embedded archived pathology block was retrieved and serially sectioned to allow histologic confirmation of lesion (first and last sections) and PCR testing of intervening sections. Extracted DNA was tested for HPV using Linear Array HPV Genotyping Test (Roche Diagnostics) with additional INNO-LiPA HPV Genotyping Assay (Innogenetics) testing on negative or inadequate specimens. All specimens were tested for a minimum 37 HPV types. Results Of 62 cervical cancer specimens evaluated, 57 (91.9%) contained one or more HPV types. Thirty-eight (61.2%) cancers contained HPV types 16 or 18, and 18 (29%) contained an oncogenic type other than type 16 or 18. Conclusions Overall, almost two-thirds (61.2%) of the archived cervical cancers had detectible HPV types 16 or 18, a finding similar to studies of US women. As expected, a proportion of cancers would not be prevented by the current vaccines. HPV vaccination and cervical cancer screening are important prevention strategies for AN women. PMID:23984281

  4. HPV genotypes detected in cervical cancers from Alaska Native women, 1980–2007

    Directory of Open Access Journals (Sweden)

    Janet J. Kelly

    2013-08-01

    Full Text Available Background. Human papillomavirus (HPV vaccine prevents cervical pre-cancers and cancers caused by HPV types 16 and 18. This study provides information on the HPV types detected in cervical cancers of Alaska Native (AN women. Methods. Cases of invasive cervical cancer diagnosed in AN women aged 18 and above between 1980 and 2007 were identified from the Alaska Native Tumor Registry. A representative formalin-fixed, paraffin-embedded archived pathology block was retrieved and serially sectioned to allow histologic confirmation of lesion (first and last sections and PCR testing of intervening sections. Extracted DNA was tested for HPV using Linear Array HPV Genotyping Test (Roche Diagnostics with additional INNO-LiPA HPV Genotyping Assay (Innogenetics testing on negative or inadequate specimens. All specimens were tested for a minimum 37 HPV types. Results. Of 62 cervical cancer specimens evaluated, 57 (91.9% contained one or more HPV types. Thirty-eight (61.2% cancers contained HPV types 16 or 18, and 18 (29% contained an oncogenic type other than type 16 or 18. Conclusions. Overall, almost two-thirds (61.2% of the archived cervical cancers had detectible HPV types 16 or 18, a finding similar to studies of US women. As expected, a proportion of cancers would not be prevented by the current vaccines. HPV vaccination and cervical cancer screening are important prevention strategies for AN women.

  5. Determination of Oncogenic Human Papillomavirus (HPV) Genotypes in Anogenital Cancers in Myanmar.

    Science.gov (United States)

    Mu Mu Shwe; Hlaing Myat Thu; Khin Saw Aye; Aye Aye Myint; Mya Thida; Khin Shwe Mar; Khin Khin Oo; Khin Sandar Aye; Okada, Shigeru; Kyaw Zin Thant

    2016-01-01

    Molecular and epidemiologic investigations suggest a causal role for human papillomavirus (HPV) in anogenital cancers. This study identified oncogenic HPV genotypes in anogenital cancers among men and women in a 2013 cross-sectional descriptive study in Myanmar. In total, 100 biopsy tissues of histologically confirmed anogenital cancers collected in 2008-2012 were studied, including 30 penile and 9 anal cancers from Yangon General Hospital and 61 vulvar cancers from Central Women's Hospital, Yangon. HPV-DNA testing and genotyping were performed by polymerase chain reaction-restriction fragment length polymorphism. Overall, 34% of anogenital cancers were HPV-positive. HPV was found in 44.4% of anal (4/9), 36.1% of vulvar (22/61), and 26.7% of penile (8/30) cancers. The most frequent genotypes in anal cancers were HPV 16 (75% ) and 18 (25% ). In vulvar cancers, HPV 33 was most common (40.9% ), followed by 16 (31.8% ), 31 (22.7% ), and 18 (4.6% ). In penile cancers, HPV 16 (62.5% ) was most common, followed by 33 (25% ) and 18 (12.5% ). This is the first report of evidencebased oncogenic HPV genotypes in anogenital cancers among men and women in Myanmar. This research provides valuable information for understanding the burden of HPV-associated cancers of the anus, penis, and vulva and considering the effectiveness of prophylactic HPV vaccination.

  6. Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection

    DEFF Research Database (Denmark)

    Olsson, Sven-Eric; Kjaer, Susanne K; Sigurdsson, Kristján

    2009-01-01

    In the quadrivalent (types 6/11/16/18) HPV vaccine (GARDASIL/SILGARD) clinical program, 73% of women aged 16-26 were naïve to all vaccine HPV types. In these women, prophylactic administration of the vaccine was highly effective in preventing HPV 6/11/16/18-related cervical disease....... Of the remaining women, 15% of had evidence of past infection with one or more vaccine HPV types (seropositive and DNA negative) at the time of enrollment. Here we present an analysis in this group of women to determine the efficacy of the HPV 6/11/16/18 vaccine against new cervical and external anogenital disease...... related to the same vaccine HPV type which had previously been cleared. Vaccine tolerability in this previously infected population was also assessed....

  7. Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection

    DEFF Research Database (Denmark)

    Olsson, Sven-Eric; Kjaer, Susanne K; Sigurdsson, Kristján

    2009-01-01

    Objective: In the quadrivalent (types 6/11/16/18) HPV vaccine (GARDASIL((R))/SILGARD((R))) clinical program, 73% of women aged 16-26 were naïve to all vaccine HPV types. In these women, prophylactic administration of the vaccine was highly effective in preventing HPV 6/11/16/18-related cervical...... disease. Of the remaining women, 15% of had evidence of past infection with one or more vaccine HPV types (seropositive and DNA negative) at the time of enrollment. Here we present an analysis in this group of women to determine the efficacy of the HPV 6/11/16/18 vaccine against new cervical and external...... anogenital disease related to the same vaccine HPV type which had previously been cleared. Vaccine tolerability in this previously infected population was also assessed. Results: Subjects were followed for an average of 40 months. Seven subjects in the placebo group developed cervical disease, and eight...

  8. Clinical validation of Anyplex™ II HPV HR Detection according to the guidelines for HPV test requirements for cervical cancer screening.

    Science.gov (United States)

    Hesselink, A T; Sahli, R; Berkhof, J; Snijders, P J F; van der Salm, M L; Agard, D; Bleeker, M C G; Heideman, D A M

    2016-03-01

    Anyplex™ II HPV HR Detection (Seegene, Seoul, Korea) is a multiplex real-time PCR using tagging oligonucleotide cleavage and extension (TOCE) technology for simultaneous detection and genotyping of 14 high-risk (HR) HPV types, including HPV16 and HPV18. To evaluate whether the clinical performance and reproducibility of Anyplex™ II HPV HR Detection meet the international consensus guidelines for HPV test requirements for cervical cancer screening [1]. The clinical performance of Anyplex™ II HPV HR Detection for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was determined relative to that of the reference assay, i.e., HR HPV GP5+/6+-PCR-EIA, by analysis of a total of 879 cervical liquid based cytology (LBC) specimens from a screening population, of which 60 were from women with CIN2+. The intra-laboratory reproducibility and inter-laboratory agreement were determined on 509 LBC samples, of which 172 were positive by the reference assay. Anyplex™ II HPV HR Detection showed a clinical sensitivity for CIN2+ of 98.3% (59/60; 95% CI: 89.1-99.8) and a clinical specificity for CIN2+ of 93.6% (764/816; 95% CI: 89.8-96.1). The clinical sensitivity and specificity were non-inferior to those of HR HPV GP5+/6+-PCR-EIA (non-inferiority score test: P=0.005 and P=0.023, respectively). Both intra-laboratory reproducibility (96.8%; 95% CI: 95.3-98.1; kappa value of 0.93) and inter-laboratory agreement (96.0%; 95% CI: 94.3-97.4; kappa value of 0.91) were high. Anyplex™ II HPV HR Detection performs clinically non-inferior to HR HPV GP5+/6+-PCR-EIA. Anyplex™ II HPV HR Detection complies with international consensus validation metrics for HPV DNA tests for cervical cancer screening [1]. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Specific Magnetic Isolation of E6 HPV16 Modified Magnetizable Particles Coupled with PCR and Electrochemical Detection.

    Science.gov (United States)

    Jimenez Jimenez, Ana Maria; Ruttkay-Nedecky, Branislav; Dostalova, Simona; Krejcova, Ludmila; Michalek, Petr; Richtera, Lukas; Adam, Vojtech

    2016-05-05

    The majority of carcinomas that were developed due to the infection with human papillomavirus (HPV) are caused by high-risk HPV types, HPV16 and HPV18. These HPV types contain the E6 and E7 oncogenes, so the fast detection of these oncogenes is an important point to avoid the development of cancer. Many different HPV tests are available to detect the presence of HPV in biological samples. The aim of this study was to design a fast and low cost method for HPV identification employing magnetic isolation, polymerase chain reaction (PCR) and electrochemical detection. These assays were developed to detect the interactions between E6-HPV16 oncogene and magnetizable particles (MPs) using commercial Dynabeads M-280 Streptavidin particles and laboratory-synthesized "homemade" particles called MANs (MAN-37, MAN-127 and MAN-164). The yields of PCR amplification of E6-HPV16 oncogene bound on the particles and after the elution from the particles were compared. A highest yield of E6-HPV16 DNA isolation was obtained with both MPs particles commercial M-280 Streptavidin and MAN-37 due to reducing of the interferents compared with the standard PCR method. A biosensor employing the isolation of E6-HPV16 oncogene with MPs particles followed by its electrochemical detection can be a very effective technique for HPV identification, providing simple, sensitive and cost-effective analysis.

  10. Specific Magnetic Isolation of E6 HPV16 Modified Magnetizable Particles Coupled with PCR and Electrochemical Detection

    Directory of Open Access Journals (Sweden)

    Ana Maria Jimenez Jimenez

    2016-05-01

    Full Text Available The majority of carcinomas that were developed due to the infection with human papillomavirus (HPV are caused by high-risk HPV types, HPV16 and HPV18. These HPV types contain the E6 and E7 oncogenes, so the fast detection of these oncogenes is an important point to avoid the development of cancer. Many different HPV tests are available to detect the presence of HPV in biological samples. The aim of this study was to design a fast and low cost method for HPV identification employing magnetic isolation, polymerase chain reaction (PCR and electrochemical detection. These assays were developed to detect the interactions between E6-HPV16 oncogene and magnetizable particles (MPs using commercial Dynabeads M-280 Streptavidin particles and laboratory-synthesized “homemade” particles called MANs (MAN-37, MAN-127 and MAN-164. The yields of PCR amplification of E6-HPV16 oncogene bound on the particles and after the elution from the particles were compared. A highest yield of E6-HPV16 DNA isolation was obtained with both MPs particles commercial M-280 Streptavidin and MAN-37 due to reducing of the interferents compared with the standard PCR method. A biosensor employing the isolation of E6-HPV16 oncogene with MPs particles followed by its electrochemical detection can be a very effective technique for HPV identification, providing simple, sensitive and cost-effective analysis.

  11. Clinical validation of the HPV-risk assay, a novel real-time PCR assay for detection of high-risk human papillomavirus DNA by targeting the E7 region.

    Science.gov (United States)

    Hesselink, A T; Berkhof, J; van der Salm, M L; van Splunter, A P; Geelen, T H; van Kemenade, F J; Bleeker, M G B; Heideman, D A M

    2014-03-01

    The HPV-Risk assay is a novel real-time PCR assay targeting the E7 region of 15 high-risk human papillomavirus (HPV) types (i.e., HPV16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -67, and -68), and provides additional genotype information for HPV16 and HPV18. This study evaluated the clinical performance and reproducibility of the HPV-Risk assay with cervical scraping specimens and its utility with self-collected (cervico)vaginal specimens. The clinical performance of the HPV-Risk assay for cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) with cervical scraping specimens was evaluated by a noninferiority analysis, relative to high-risk HPV GP5+/6+ PCR, following international guidelines for HPV test requirements for cervical cancer screening. The HPV-Risk assay showed clinical sensitivity for CIN2+ of 97.1% (95% confidence interval [CI], 89.1 to 99.3%; 67/69 samples) and a clinical specificity for CIN2+ of 94.3% (95% CI, 92.5 to 95.7%; 777/824 samples). The clinical sensitivity and specificity were noninferior to those of GP5+/6+ PCR (noninferiority score test, P=0.006 and 0.0003, respectively). Intralaboratory reproducibility over time (99.5% [95% CI, 98.6 to 99.8%]; 544/547 samples, kappa=0.99) and interlaboratory agreement (99.2% [95% CI, 98.6 to 99.8%]; 527/531 samples, kappa=0.98) for the HPV-Risk assay with cervical scraping specimens were high. The agreement of the HPV-Risk assay results for self-collected (cervico)vaginal specimens and clinician-obtained cervical scraping specimens was also high, i.e., 95.9% (95% CI, 85.1 to 99.0%; 47/49 samples, kappa=0.90) for self-collected lavage samples and 91.6% (95% CI, 84.6 to 95.6%; 98/107 samples, kappa=0.82) for self-collected brush samples. In conclusion, the HPV-Risk assay meets the cross-sectional clinical and reproducibility criteria of the international guidelines for HPV test requirements and can be considered clinically validated for cervical screening purposes. The

  12. Re-engineering and evaluation of anti-DNA autoantibody 3E10 for therapeutic applications.

    Science.gov (United States)

    Rattray, Zahra; Dubljevic, Valentina; Rattray, Nicholas J W; Greenwood, Deanne L; Johnson, Caroline H; Campbell, James A; Hansen, James E

    2018-01-29

    A key challenge in the development of novel chemotherapeutics is the design of molecules capable of selective toxicity to cancer cells. Antibodies have greater target specificity compared to small molecule drugs, but most are unable to penetrate cells, and predominantly target extracellular antigens. A nuclear-penetrating anti-DNA autoantibody isolated from the MRL/lpr lupus mouse model, 3E10, preferentially localizes to tumors, inhibits DNA repair, and selectively kills cancer cells with defects in DNA repair. A murine divalent single chain variable fragment of 3E10 with mutations for improved DNA binding affinity, 3E10 (D31N) di-scFv, has previously been produced in P. pastoris and yielded promising pre-clinical findings, but is unsuitable for clinical testing. The present study reports the design, expression and testing of a panel of humanized 3E10 (D31N) di-scFvs, some of which contain CDR substitution. These variants were expressed in a modified CHO system and evaluated for their physicochemical attributes and ability to penetrate nuclei to selectively cause DNA damage accumulation in and kill cancer cells with DNA repair defects. Secondary structure was conserved and most variants retained the key characteristics of the murine 3E10 (D31N) di-scFv produced in P. pastoris. Moreover, several variants with CDR substitutions outperformed the murine prototype. In conclusion, we have designed several humanized variants of 3E10 (D31N) di-scFv that have potential for application as monotherapy or conjugates for targeted nuclear drug delivery. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. Enhanced gene expression of systemically administered plasmid DNA inthe liver with therapeutic ultrasound and microbubbles

    NARCIS (Netherlands)

    Raju, B.I.; Leyvi, E.; Seip, R.; Sethuraman, S.; Luo, X.; Bird, A.; Li, S.; Koeberl, D.

    2012-01-01

    Ultrasound mediated delivery (USMD) of novel therapeutic agents in the presence of microbubbles is a potentially safe and effective method for gene therapy offering many desired characteristics such as low toxicity, potential for repeated treatment, and organ specificity.In this study we tested the

  14. A Live Vector Expressing HPV16 L1 Generates an Adjuvant-Induced Antibody Response In-vivo.

    Science.gov (United States)

    Shirbaghaee, Zeinab; Bolhassani, Azam; Mirshafiey, Abbas; Motevalli, Fatemeh; Zohrei, Negar

    2015-12-01

    The association between human papillomavirus (HPV) infections and cervical cancer has suggested the design of prophylactic and therapeutic vaccines against genital warts. The HPV capsid has made of two L1 and L2 coat proteins that have produced late in viral infections. Regarding to the recent studies, two commercial prophylactic vaccines have based on L1 viral like particles (VLPs) could strongly induce antibody responses, and protect human body from HPV infections. However, the use of these HPV vaccines has hindered due to their high cost and some limitations. Currently, among various vaccination strategies, live vector-based vaccines have attracted a great attention. Herein, a non-pathogenic strain of the protozoan organism known as Leishmania tarentolae has utilized to induce potent humoral immunity in mice model. At first, cloning of HPV16 L1 gene into Leishmania expression vector has performed and confirmed by PCR and digestion with restriction enzymes. The promastigotes of Leishmania tarentolae (L.tar) have transfected with linearized DNA construct by electroporation. Protein expression has analyzed by SDS-PAGE and western blotting. Then, the immunogenicity of leishmania expressing L1 protein (L.tar-L1) has assessed in mice model. Our data has indicated that subcutaneous immunization of mice with the recombinant L.tar-L1 has led to enhance the levels of IgG1 and lgG2a in comparison with control groups. Furthermore, there was no significant increase in antibody levels between two and three times of immunizations. The recombinant live vector was able to induce humoral immunity in mice without need of any adjuvant. However, further studies have required to increase its efficiency.

  15. HPV Involvement in Head and Neck Cancers: Comprehensive Assessment of Biomarkers in 3680 Patients.

    Science.gov (United States)

    Castellsagué, Xavier; Alemany, Laia; Quer, Miquel; Halec, Gordana; Quirós, Beatriz; Tous, Sara; Clavero, Omar; Alòs, Llúcia; Biegner, Thorsten; Szafarowski, Tomasz; Alejo, Maria; Holzinger, Dana; Cadena, Enrique; Claros, Edith; Hall, Gillian; Laco, Jan; Poljak, Mario; Benevolo, Maria; Kasamatsu, Elena; Mehanna, Hisham; Ndiaye, Cathy; Guimerà, Núria; Lloveras, Belen; León, Xavier; Ruiz-Cabezas, Juan C; Alvarado-Cabrero, Isabel; Kang, Chang-Suk; Oh, Jin-Kyoung; Garcia-Rojo, Marcial; Iljazovic, Ermina; Ajayi, Oluseyi F; Duarte, Flora; Nessa, Ashrafun; Tinoco, Leopoldo; Duran-Padilla, Marco A; Pirog, Edyta C; Viarheichyk, Halina; Morales, Hesler; Costes, Valérie; Félix, Ana; Germar, Maria Julieta V; Mena, Marisa; Ruacan, Arzu; Jain, Asha; Mehrotra, Ravi; Goodman, Marc T; Lombardi, Luis Estuardo; Ferrera, Annabelle; Malami, Sani; Albanesi, Estela I; Dabed, Pablo; Molina, Carla; López-Revilla, Rubén; Mandys, Václav; González, Manuel E; Velasco, Julio; Bravo, Ignacio G; Quint, Wim; Pawlita, Michael; Muñoz, Nubia; de Sanjosé, Silvia; Xavier Bosch, F

    2016-06-01

    We conducted a large international study to estimate fractions of head and neck cancers (HNCs) attributable to human papillomavirus (HPV-AFs) using six HPV-related biomarkers of viral detection, transcription, and cellular transformation. Formalin-fixed, paraffin-embedded cancer tissues of the oral cavity (OC), pharynx, and larynx were collected from pathology archives in 29 countries. All samples were subject to histopathological evaluation, DNA quality control, and HPV-DNA detection. Samples containing HPV-DNA were further subject to HPV E6*I mRNA detection and to p16(INK4a), pRb, p53, and Cyclin D1 immunohistochemistry. Final estimates of HPV-AFs were based on HPV-DNA, HPV E6*I mRNA, and/or p16(INK4a) results. A total of 3680 samples yielded valid results: 1374 pharyngeal, 1264 OC, and 1042 laryngeal cancers. HPV-AF estimates based on positivity for HPV-DNA, and for either HPV E6*I mRNA or p16(INK4a), were 22.4%, 4.4%, and 3.5% for cancers of the oropharynx, OC, and larynx, respectively, and 18.5%, 3.0%, and 1.5% when requiring simultaneous positivity for all three markers. HPV16 was largely the most common type. Estimates of HPV-AF in the oropharynx were highest in South America, Central and Eastern Europe, and Northern Europe, and lowest in Southern Europe. Women showed higher HPV-AFs than men for cancers of the oropharynx in Europe and for the larynx in Central-South America. HPV contribution to HNCs is substantial but highly heterogeneous by cancer site, region, and sex. This study, the largest exploring HPV attribution in HNCs, confirms the important role of HPVs in oropharyngeal cancer and drastically downplays the previously reported involvement of HPVs in the other HNCs. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Correlation of LMP10 expression and clinical outcome in Human Papillomavirus (HPV positive and HPV-Negative tonsillar and base of tongue cancer.

    Directory of Open Access Journals (Sweden)

    Nikolaos Tertipis

    Full Text Available To examine LMP10 expression and its possible impact on clinical outcome in human papillomavirus (HPV positive and HPV-negative tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC.Outcome is better in HPV-positive TSCC and BOTSCC compared to matching HPV-negative tumours, with roughly 80% vs. 40% 5-year disease free survival (DFS with less aggressive treatment than today's chemoradiotherapy. Since current treatment often results in harmful side effects, less intensive therapy, with sustained patient survival would be an attractive alternative. However, other markers together with HPV status are necessary to select patients and for this purpose LMP10 expression is investigated here in parallel to HPV status and clinical outcome.From 385 patients diagnosed between 2000 and 2007 at the Karolinska University Hospital, 278 formalin fixed paraffin embedded TSCC and BOTSCC biopsies, with known HPV DNA status, were tested for LMP10 nuclear and cytoplasmic expression (fraction of positive cells and staining intensity. The data was then correlated to clinical outcome.An absent/low compared to a moderate/high LMP10 nuclear fraction of positive cells was correlated to a better 3-year DFS in the HPV-positive group of patients (log-rank p = 0.005, but not in the HPV-negative group. In the HPV-negative group of patients, in contrast to the HPV-positive group, moderate/high LMP10 cytoplasmic fraction and weak/moderate/high LMP10 cytoplasmic intensity correlated to a better 3-year DFS (p = 0.003 and p = 0.001 and 3-year overall survival (p = 0.001 and 0.009.LMP10 nuclear expression in the HPV-positive group and LMP10 cytoplasmic expression in the HPV-negative group of patients correlated to better clinical outcome.

  17. Correlation of LMP10 expression and clinical outcome in Human Papillomavirus (HPV) positive and HPV-Negative tonsillar and base of tongue cancer.

    Science.gov (United States)

    Tertipis, Nikolaos; Haeggblom, Linnea; Nordfors, Cecilia; Grün, Nathalie; Näsman, Anders; Vlastos, Andrea; Dalianis, Tina; Ramqvist, Torbjörn

    2014-01-01

    To examine LMP10 expression and its possible impact on clinical outcome in human papillomavirus (HPV) positive and HPV-negative tonsillar and base of tongue squamous cell carcinoma (TSCC and BOTSCC). Outcome is better in HPV-positive TSCC and BOTSCC compared to matching HPV-negative tumours, with roughly 80% vs. 40% 5-year disease free survival (DFS) with less aggressive treatment than today's chemoradiotherapy. Since current treatment often results in harmful side effects, less intensive therapy, with sustained patient survival would be an attractive alternative. However, other markers together with HPV status are necessary to select patients and for this purpose LMP10 expression is investigated here in parallel to HPV status and clinical outcome. From 385 patients diagnosed between 2000 and 2007 at the Karolinska University Hospital, 278 formalin fixed paraffin embedded TSCC and BOTSCC biopsies, with known HPV DNA status, were tested for LMP10 nuclear and cytoplasmic expression (fraction of positive cells and staining intensity). The data was then correlated to clinical outcome. An absent/low compared to a moderate/high LMP10 nuclear fraction of positive cells was correlated to a better 3-year DFS in the HPV-positive group of patients (log-rank p = 0.005), but not in the HPV-negative group. In the HPV-negative group of patients, in contrast to the HPV-positive group, moderate/high LMP10 cytoplasmic fraction and weak/moderate/high LMP10 cytoplasmic intensity correlated to a better 3-year DFS (p = 0.003 and p = 0.001) and 3-year overall survival (p = 0.001 and 0.009). LMP10 nuclear expression in the HPV-positive group and LMP10 cytoplasmic expression in the HPV-negative group of patients correlated to better clinical outcome.

  18. IL-10 gene polymorphism c.-592C>A increases HPV infection susceptibility and influences IL-10 levels in HPV infected women.

    Science.gov (United States)

    Berti, Fernanda Costa Brandão; Pereira, Ana Paula Lombardi; Trugilo, Kleber Paiva; Cebinelli, Guilherme Cesar Martelossi; Silva, Lorena Flor da Rosa Santos; Lozovoy, Marcell Alysson Batisti; Simão, Andréa Name Colado; Watanabe, Maria Angelica Ehara; de Oliveira, Karen Brajão

    2017-09-01

    Interleukin-10 (IL-10) influences HPV infection and viral persistence, favoring cervical immunosuppression and cervical carcinogenesis. IL-10 levels may be influenced by HPV itself and by IL-10 polymorphisms, including rs1800872 (c.-592C>A). Therefore, we evaluated the influence of IL-10 c.-592C>A polymorphism in HPV infection and in IL-10 plasmatic/cervical levels in HPV infected and non-infected women. The study included 174 infected and 186 non-infected patients. Cervical epithelial scrapings were obtained to determine HPV DNA presence PCR. Peripheral blood samples were obtained to determine IL-10 polymorphism by PCR-RFLP, while IL-10 levels were assessed by ELISA. HPV was more prevalent among allele A carriers (pA polymorphism being associated with HPV infection. As demonstrated by binary logistic regression analysis, heterozygotes [ORadj=2.081 95% CI (1.222-3.544), p=0.007] and homozygotes [ORadj=3.745 95% CI (1.695-8.271), p=0.001] showed approximately 2 and 4 time's greater odds, respectively, of presenting HPV when compared to CC patients. Moreover, HPV infected patients carrying polymorphic allele A showed higher IL-10 cervical levels (p=0.039). Binary logistic regression analysis demonstrated that IL-10 cervical levels were not independently associated to CA+AA genotypes (p=0.162), neither to HPV's presence (p=0.061), thus IL-10 cervical levels are possibly increased because of both HPV and allele A presence. Taken together, these findings suggest that IL-10 c.-592C>A polymorphism is independently associated with HPV infection susceptibility exerting influence on IL-10 cervical levels in HPV infected women, thus contributing to cervical carcinogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. HPV Vaccine - Questions and Answers

    Science.gov (United States)

    ... and Media Resources News Newsletters Events Redirect for HPV Vaccine FAQ Recommend on Facebook Tweet Share Compartir ... to the address below. http://www.cdc.gov/hpv/parents/questions-answers.html File Formats Help: How ...

  20. A review of cross-protection against oncogenic HPV by an HPV-16/18 AS04-adjuvanted cervical cancer vaccine: importance of virological and clinical endpoints and implications for mass vaccination in cervical cancer prevention.

    Science.gov (United States)

    Jenkins, David

    2008-09-01

    Human papilloma virus (HPV)-16 and -18 are responsible for approximately 70% of invasive cervical cancers worldwide. Other oncogenic HPV types account for almost all the remainder. Importantly, HPV-45 and -31 account for approximately 10%. HPV-18 and -45, along with HPV-16, are found in over 90% of endocervical adenocarcinomas. HPV-45 is the third most frequent HPV type in cervical carcinoma and adenocarcinoma. The AS04-adjuvanted vaccine Cervarix was developed against HPV-16 and -18 focusing on preventing cervical cancer by inducing durable protection against new infection. In clinical trials, it shows evidence of cross-protection against other important oncogenic HPV types using a range of clinicopathological and virological endpoints. The current evidence suggesting the cross-protective effect comes from its overall impact on precancerous lesions and on 12-month or more persistent oncogenic HPV infection, together with specific evidence of protection against incident and new persistent infection lasting 6 months or more with individual HPV types. The use of virological endpoints for such studies is discussed, in particular for cross-protection evaluation, in view of the lower frequency of many important oncogenic HPV types other than HPV-16 or -18 in precancerous lesions and the frequent presence of multiple HPV infections. Both of these factors complicate the interpretation of type-specific, vaccine-induced protection against cervical intraepithelial neoplasia (CIN) lesions, in which other HPV DNA types are found along with HPV-16 and -18. The observed high level of overall protection against clinicopathological lesions, including CIN2+ in the vaccinated subjects (regardless of their HPV DNA status), predicts a potentially broader impact of the vaccine in the prevention of HPV-related precancers that goes beyond HPV-16 and -18. The prevention of persistent infections by individual types such as HPV-45 provides specific information on the protection against that

  1. Human Papillomavirus (HPV) Prevalence in Nasal and Antrochoanal Polyps and Association with Clinical Data.

    Science.gov (United States)

    Knör, Mareike; Tziridis, Konstantin; Agaimy, Abbas; Zenk, Johannes; Wendler, Olaf

    2015-01-01

    The pathogenesis of sinonasal polyposis remains unclear, in spite of several investigative approaches. Antrochoanal polyps, a subgroup of sinonasal polyposis along with allergic- and chronic-inflammatory nasal polyps, mostly originate from the maxillary sinus and develop as a unilateral, pedunculated mass towards the nasopharynx. The human papillomavirus (HPV) is discussed as a possible causative and influencing factor in development and progression of sinonasal polyposis. This study aims to elucidate HPV frequency in nasal polyps and antrochoanal polyps. Genomic DNA from 257 tissue specimens (166 nasal polyps, 39 antrochoanal polyps and 52 nasal turbinates) was subjected to three different established HPV- polymerase chain reaction assays, testing for 37 low- and high-risk HPV. In addition, immunohistochemical analyses for HPV16 were carried out, as well as immunohistochemistry and western blots of p16, a biomarker for HPV induced cancer. HPV-DNA was detected in 53.8% of antrochoanal polyps, 15.1% of nasal polyps, and 5.8% of nasal turbinates. HPV16 was the predominant type with a detection rate of 76% in nasal polyps and 62% in antrochoanal polyps. Immunohistochemically, HPV positive tissues stained positive for HPV16 antigens and p16 in epithelial cell layers. No significant p16 overexpression was traceable in antrochoanal polyps, nasal polyps and nasal turbinates by western blot. There was no correlation of HPV-status with sex, age, smoking, alcohol consumption or allergic background. The present study shows a significant frequency of high-risk type HPV16 in antrochoanal polyps. Absence of oncogenic transformation or correlation of the HPV-status with clinical data suggests a latent superinfection, possibly because of anatomical proximity to the oropharynx.

  2. Human Papillomavirus (HPV Prevalence in Nasal and Antrochoanal Polyps and Association with Clinical Data.

    Directory of Open Access Journals (Sweden)

    Mareike Knör

    Full Text Available The pathogenesis of sinonasal polyposis remains unclear, in spite of several investigative approaches. Antrochoanal polyps, a subgroup of sinonasal polyposis along with allergic- and chronic-inflammatory nasal polyps, mostly originate from the maxillary sinus and develop as a unilateral, pedunculated mass towards the nasopharynx. The human papillomavirus (HPV is discussed as a possible causative and influencing factor in development and progression of sinonasal polyposis. This study aims to elucidate HPV frequency in nasal polyps and antrochoanal polyps.Genomic DNA from 257 tissue specimens (166 nasal polyps, 39 antrochoanal polyps and 52 nasal turbinates was subjected to three different established HPV- polymerase chain reaction assays, testing for 37 low- and high-risk HPV. In addition, immunohistochemical analyses for HPV16 were carried out, as well as immunohistochemistry and western blots of p16, a biomarker for HPV induced cancer.HPV-DNA was detected in 53.8% of antrochoanal polyps, 15.1% of nasal polyps, and 5.8% of nasal turbinates. HPV16 was the predominant type with a detection rate of 76% in nasal polyps and 62% in antrochoanal polyps. Immunohistochemically, HPV positive tissues stained positive for HPV16 antigens and p16 in epithelial cell layers. No significant p16 overexpression was traceable in antrochoanal polyps, nasal polyps and nasal turbinates by western blot. There was no correlation of HPV-status with sex, age, smoking, alcohol consumption or allergic background.The present study shows a significant frequency of high-risk type HPV16 in antrochoanal polyps. Absence of oncogenic transformation or correlation of the HPV-status with clinical data suggests a latent superinfection, possibly because of anatomical proximity to the oropharynx.

  3. Continuing rise in oropharyngeal cancer in a high HPV prevalence area: A Danish population-based study from 2011 to 2014.

    Science.gov (United States)

    Carlander, Amanda-Louise Fenger; Grønhøj Larsen, Christian; Jensen, David Hebbelstrup; Garnæs, Emilie; Kiss, Katalin; Andersen, Luise; Olsen, Caroline Holkmann; Franzmann, Maria; Høgdall, Estrid; Kjær, Susanne K; Norrild, Bodil; Specht, Lena; Andersen, Elo; van Overeem Hansen, Thomas; Nielsen, Finn Cilius; von Buchwald, Christian

    2017-01-01

    Human papillomavirus (HPV) is a critical element in the rising incidence of oropharyngeal squamous cell carcinoma (OPSCC), although whether this trend will continue, and the types of HPV responsible, are currently unknown. We previously demonstrated an increased incidence of HPV-related OPSCC in the high HPV prevalence area of Eastern Denmark from 2000 to 2010. Therefore, we investigated if the incidence for OPSCC continued to rise, the association to HPV and putative HPV-types in Eastern Denmark from 2011 to 14. We then projected the expected incidence of OPSCC versus cervical cancer through to 2020. Patients with OPSCC (tonsillar squamous cell carcinoma [TSCC] and base of tongue squamous cell carcinoma [BSCC]) were identified via the Danish Head and Neck Cancer Group and the Danish Pathology Databank (n = 700). Tumours were re-reviewed and assessed using p16 immunohistochemistry, HPV DNA polymerase chain reaction (PCR), with genotyping by next generation sequencing. Sixty-two percent (432/700) of tumours were HPV-positive (HPV+). The total incidence rate (per 100.000) for OPSCC increased from 4.0 in 2011 to 4.5 in 2014, primarily due to a rise in HPV+ TSCCs and HPV+ BSCCs, although numbers of HPV-negative (HPV-) OPSCC also increased during the study period. The majority of HPV+ tumours were HPV16 DNA positive (86%), but we also identified HPV33 DNA (6%), HPV35 DNA (4%) and others (3%), including HPV18, 26, 31, 45, 56, 58, 59 and HPV67. An increasing incidence of OPSCC is driven primarily by HPV+ OPSCC. Sixty-two percent of tumours were HPV+, which is a high-prevalence, although the lower number of HPV- cases has yet to stabilise. HPV16 was the predominant genotype, although a significant proportion (14%) was of another genotype. Our projections suggest that the number of HPV+ OPSCC will exceed that of cervical cancer in 2016 in Eastern Denmark. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. HPV vaccines: a controversial issue?

    OpenAIRE

    Nicol, A.F.; Andrade, C.V.; Russomano, F.B.; Rodrigues, L.L.S.; Oliveira, N.S.; D.W. Provance Jr

    2016-01-01

    Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment o...

  5. Impact of vaccine protection against multiple HPV types on the cost-effectiveness of cervical screening.

    Science.gov (United States)

    Coupé, Veerle M H; Bogaards, Johannes A; Meijer, Chris J L M; Berkhof, Johannes

    2012-02-27

    Cross-protection against non-HPV16/18 types and the emergence of broad spectrum vaccines protecting against multiple HPV types will influence the cost-effectiveness of future screening. To assess this influence we used an individual-based simulation model describing the relation between 14 HPV types and cervical disease, allowing the occurrence of multiple type infections. Screening scenarios for vaccinated women were evaluated, firstly for HPV16/18 vaccination with partial cross-protection against HPV 31, 33, 45 and 58 and secondly, for broad spectrum vaccination against 5-13 HPV types. The vaccine-induced incidence reduction of type-specific infection was varied from 0 to 95% in the cross-protection setting and set at 100% in the setting of broad spectrum vaccines. Scenarios of either cytology or HPV DNA screening were considered under varying lifetime number of screening rounds. At a cost-effectiveness threshold of €20,000/QALY, four times HPV DNA screening between 30 and 60 years was the selected scenario in addition to HPV16/18 vaccination, whether or not cross-protection was conferred (€6707 and €9994/QALY, respectively). In the absence of cross-protection, a fifth screening round might be considered (ICER €22,967/QALY). In addition to broad spectrum vaccination, one screen during lifetime was cost-effective up to an 11-valent vaccine. If the vaccine-induced type-specific incidence reduction was lowered to 99%, one screen during lifetime was cost-effective even in addition to 13-valent vaccination. In conclusion, in a cohort of HPV16/18 vaccinated women, four rounds of HPV DNA screening is cost-effective. One screen during lifetime remains cost-effective in addition to broad spectrum vaccination offering protection against many high-risk HPV types. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. HPV infection in women: psychosexual impact of genital warts and intraepithelial lesions.

    Science.gov (United States)

    Graziottin, Alessandra; Serafini, Audrey

    2009-03-01

    Genital Human Papillomavirus (HPV) infection is the most commonly occurring sexually transmitted viral infection in humans. HPV is a wide family of DNA viruses, which may cause benign skin and mucosal tumors (genital, anal, or oral warts), intraepithelial neoplasias, and/or malignant cancers in different organs. Women are more susceptible to the oncogenic effect of HPVs, mostly at the genital site on the uterine cervix. This review analyzes the impact of: (i) genital warts (GWs) and their treatment; (ii) HPV-related genital, oral, and anal precancerous lesions on women's sexual function. A Medline search was carried out. Search terms were HPV, GWs, intraepithelial neoplasia, cervical cancer, anal cancer, oral cancer, epidemiology, HPV risk factors, sexual dysfunctions, desire disorders, arousal disorders, dyspareunia, vulvar vestibulitis, vulvodynia, orgasmic difficulties, sexual repertoire, couple sexual problems, depression, anxiety, pap smear, screening program, therapy, and vaccines. Sexual consequences of HPV infection in women, specifically GWs and intraepithelial HPV-related neoplasia. Psychosexual vulnerability increases with number of recurrences of HPV infections. Depression, anxiety, and anger are the emotions most frequently reported. However, to date, there is no conclusive evidence of a specific correlation between HPV infection and a specific female sexual disorder. The relationship between HPV and vulvar vestibulitis/vulvodynia-related dyspareunia seems not to be direct. Counseling problems, the role of anti-HPV vaccine, and the concept of the high-risk partner are discussed. The reader is offered a practical approach with clinically relevant recommendations that may prove useful in his/her daily practice when dealing with HPV-infected women and couples. The evidence of psychosexual consequences of HPV-related GWs and intraepithelial lesions is limited. Specific research on the sexual impact of GWs and intraepithelial HPV-related lesion in women is

  7. Smokeless tobacco increases aneuploidy in oral HPV16 E6/E7-transformed keratinocytes in vitro.

    Science.gov (United States)

    Merne, Marina; Rautava, Jaana; Ruutu, Merja; Syrjänen, Stina

    2014-10-01

    The scope of this work was to study synergism between human papillomavirus (HPV) infection and tobacco in vitro, both known to be independent risk factors for oral cancer. HPV-positive and HPV-negative oral keratinocytes and oral HPV-negative fibroblasts were exposed to smokeless tobacco extract (STE) prepared from the Scandinavian (STE1) and US-type (STE2) snuff. Cell cycle profiles were determined with flow cytometry, and HPV E6/E7 mRNA expression in HPV-positive cells was assayed using RT-qPCR. The exposure of HPV-positive keratinocytes with STE2 increased the number of aneuploid cells from 27% to 80% of which 44% were in S-phase, while none of the diploid cells were in S-phase. The changes after STE1 exposure were less than seen after STE2: from 27% to 31% of which 34% were in S-phase. STE had no effect on HPV16 E6/E7 expression in HPV-positive keratinocytes. In oral spontaneously transformed, HPV-negative keratinocytes, the number of aneuploid cells at G2-M stage increased after STE1 and STE2 exposure from 3% to 9% and 7%, respectively. In HPV-negative oral fibroblasts, the number of cells at G2-M phase increased from 11% to 21% after STE1 and 29% after STE2 exposure. The effect of STE varied in the cell lines studied. STE2 increased significantly the proportion of aneuploid cells in HPV-positive oral keratinocytes, but not HPV16 E6/E7 expression. This indicates that tobacco products may enhance the effects of HPV 16 and the risk of DNA aneuploidy increasing risk to malignant transformation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Increasing incidence of base of tongue cancers from 2000 to 2010 due to HPV

    DEFF Research Database (Denmark)

    Garnaes, E; Kiss, K; Andersen, L

    2015-01-01

    BACKGROUND: We assessed the development in the number of new base of tongue squamous-cell carcinoma (BSCC) cases per year in eastern Denmark from 2000 to 2010 and whether HPV may explain any observable increased incidence. METHODS: We performed HPV DNA PCR and p16 immunohistochemistry analysis......-positive BSCCs may explain the increasing incidence of BSCCs in eastern Denmark, 2000-2010....

  9. Perinatal transmission of human papilomavirus DNA.

    Science.gov (United States)

    Rombaldi, Renato L; Serafini, Eduardo P; Mandelli, Jovana; Zimmermann, Edineia; Losquiavo, Kamille P

    2009-06-21

    The purpose was to study the perinatal transmission of human papillomavirus DNA (HPV-DNA) in 63 mother-newborn pairs, besides looking at the epidemiological factors involved in the viral DNA transmission. The following sampling methods were used: (1) in the pregnant woman, when was recruited, in cervix and clinical lesions of the vagina, vulva and perineal region; (2) in the newborn, (a) buccal, axillary and inguinal regions; (b) nasopharyngeal aspirate, and (c) cord blood; (3) in the children, buccal was repeated in the 4th week and 6th and 12th month of life. HPV-DNA was identified using two methodologies: multiplex PCR (PGMY09 and MY11 primers) and nested-PCR (genotypes 6/11, 16, 18, 31, 33, 42, 52 and 58). Perinatal transmission was considered when concordance was found in type-specific HPV between mother/newborn or mother/child. HPV-DNA genital was detected in 49 pregnant women submitted to delivery. Eleven newborns (22.4%, n = 11/49) were HPV-DNA positive. In 8 cases (16.3%, n = 8/49) there was type specific HPV concordance between mother/newborn samples. At the end of the first month of life three children (6.1%, n = 3/49) became HPV-DNA positive, while two remained positive from birth. In 3 cases (100%, n = 3/3) there was type specific HPV concordance between mother/newborn samples. In the 6th month, a child (2%, n = 1/49) had become HPV-DNA positive between the 1st and 6th month of life, and there was type specific HPV concordance of mother/newborn samples. All the HPV-DNA positive children (22.4%, n = 11/49) at birth and at the end first month of life (6.1%, n = 3/49) became HPV-DNA negative at the age of 6 months. The HPV-DNA positive child (2%, n = 1/49) from 1st to the 6th month of life became HPV-DNA negative between the 6th and 12th month of life and one child had anogenital warts. In the twelfth month all (100%, n = 49/49) the children studied were HPV-DNA negative. A positive and significant correlation was observed between perinatal transmission

  10. Perinatal transmission of human papilomavirus DNA

    Directory of Open Access Journals (Sweden)

    Serafini Eduardo P

    2009-06-01

    Full Text Available Abstract The purpose was to study the perinatal transmission of human papillomavirus DNA (HPV-DNA in 63 mother-newborn pairs, besides looking at the epidemiological factors involved in the viral DNA transmission. The following sampling methods were used: (1 in the pregnant woman, when was recruited, in cervix and clinical lesions of the vagina, vulva and perineal region; (2 in the newborn, (a buccal, axillary and inguinal regions; (b nasopharyngeal aspirate, and (c cord blood; (3 in the children, buccal was repeated in the 4th week and 6th and 12th month of life. HPV-DNA was identified using two methodologies: multiplex PCR (PGMY09 and MY11 primers and nested-PCR (genotypes 6/11, 16, 18, 31, 33, 42, 52 and 58. Perinatal transmission was considered when concordance was found in type-specific HPV between mother/newborn or mother/child. HPV-DNA genital was detected in 49 pregnant women submitted to delivery. Eleven newborns (22.4%, n = 11/49 were HPV-DNA positive. In 8 cases (16.3%, n = 8/49 there was type specific HPV concordance between mother/newborn samples. At the end of the first month of life three children (6.1%, n = 3/49 became HPV-DNA positive, while two remained positive from birth. In 3 cases (100%, n = 3/3 there was type specific HPV concordance between mother/newborn samples. In the 6th month, a child (2%, n = 1/49 had become HPV-DNA positive between the 1st and 6th month of life, and there was type specific HPV concordance of mother/newborn samples. All the HPV-DNA positive children (22.4%, n = 11/49 at birth and at the end first month of life (6.1%, n = 3/49 became HPV-DNA negative at the age of 6 months. The HPV-DNA positive child (2%, n = 1/49 from 1st to the 6th month of life became HPV-DNA negative between the 6th and 12th month of life and one child had anogenital warts. In the twelfth month all (100%, n = 49/49 the children studied were HPV-DNA negative. A positive and significant correlation was observed between perinatal

  11. A comparison of human papillomavirus genotype-specific DNA and E6/E7 mRNA detection to identify anal precancer among HIV-infected men who have sex with men

    National Research Council Canada - National Science Library

    Castle, Philip E; Follansbee, Stephen; Borgonovo, Sylvia; Tokugawa, Diane; Schwartz, Lauren M; Lorey, Thomas S; LaMere, Brandon; Gage, Julia C; Fetterman, Barbara; Darragh, Teresa M; Rodriguez, Ana Cecilia; Wentzensen, Nicolas

    2013-01-01

    Human papillomavirus (HPV) RNA detection is reportedly more specific for the detection of anogenital precancer than HPV DNA but it is unknown whether this is due to detection of RNA or due to HPV genotype restriction...

  12. Post-hysterectomy vaginal cuff cancer secondary to HPV infection and CIN: A case report.

    Science.gov (United States)

    Liu, Xiaoxia; Yue, Ying; Zong, Shan

    2013-07-01

    We present a case report of secondary vaginal cancer after complete hysterectomy due to myoma that was complicated by low-grade cervical intraepithelial neoplasia (CIN I) and human papilloma virus (HPV) infection. After complete hysterectomy, the HPV DNA level in the vaginal tissue was obviously increased, and vaginal cancer was diagnosed 6 months later. We conclude that HPV infection can cause vaginal cancer after complete hysterectomy in cases complicated by CIN. Therefore, HPV should be regularly assessed during the postoperative follow-up period.

  13. HPV vaccines to prevent cervical cancer and genital warts: an update.

    Science.gov (United States)

    Dochez, Carine; Bogers, Johannes J; Verhelst, Rita; Rees, Helen

    2014-03-20

    Cervical cancer is an important public health problem worldwide, and especially in developing countries. The link between cervical cancer and oncogenic human papillomavirus (HPV) infection has been clearly established. Furthermore, non-oncogenic HPV are responsible for the majority of genital warts. Two prophylactic HPV vaccines are available, which have the potential of considerably reducing HPV-related morbidity and mortality. Both vaccines are based on virus-like particles of the L1 capsid protein, and are highly efficacious and immunogenic if given before exposure to HPV, i.e. to adolescent girls between 9 and 13 years of age in a three-dose schedule. This review describes the immunology of natural HPV infections and the immune response evoked through vaccination. The current duration of protection is 8.4 years with the bivalent vaccine (HPV16/18) and 5 years with the quadrivalent vaccine (HPV6/11/16/18). Research is on-going to evaluate the efficacy of the current vaccines in a two-dose schedule, as compared to the recommended three-dose schedule. To increase the protection, the development and testing of a nine-valent prophylactic HPV vaccine (HPV6/11/16/18/31/33/45/52/58) is being undertaken. Research is also directed towards therapeutic vaccines and the development of a prophylactic L2 vaccine. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Low prevalence of HPV detection and genotyping in non-muscle invasive bladder cancer using single-step PCR followed by reverse line blot.

    Science.gov (United States)

    Pichler, Renate; Borena, Wegene; Schäfer, Georg; Manzl, Claudia; Culig, Zoran; List, Sebastian; Neururer, Sabrina; Von Laer, Dorothee; Heidegger, Isabel; Klocker, Helmut; Horninger, Wolfgang; Steiner, Hannes; Brunner, Andrea

    2015-12-01

    To clarify the role of human papillomavirus (HPV) in non-muscle invasive bladder cancer, HPV-DNA was scrutinized in formalin-fixed, paraffin-embedded (FFPE) bladder cancer tissue using single-step PCR (HPV L1) for HPV detection, followed by reverse line blot (RLB) for genotyping. A total of 186 patients who underwent transurethral resection of the bladder due to primary, non-muscle invasive bladder cancer from 2006 to 2009 were reviewed. A positive control group of 22 cervical tissues with cervical carcinoma was included. Histology confirmed urothelial carcinoma in all patients: primary CIS, pTa, pT1 and pTa + pT1 in 14 (7.5 %), 134 (72 %), 36 (19.4 %) and two (1.1 %) patients, respectively. A total of 119 (63.9 %) of them were classified as low-risk, while 67 (36.1 %) were high-risk cancers. Tumor recurrence and progression (≥pT2) were seen in 79 and 11 patients (mean follow-up 45 months). The presence of HPV-DNA by single-step PCR was detected in four (2.2 %) patients. HPV 16 and HPV 6 were positive in two (1.1 %) and one (0.6 %) patient, respectively In one case, no HPV genotype listed on the RLB assay could be identified. In the control group, the HPV infection rate was 100 %: HPV 16 in 12 (54.6 %) patients, HPV 16/18 in four (18.3 %) patients, HPV 18 in two (9.1 %) patients, HPV 16/45 in one patient (4.5 %), HPV 18/33 in one (4.5 %) patient, HPV 16/33 in one (4.5 %) patient and HPV 33 in one (4.5 %) patient. Our study demonstrates low prevalence of HPV infection in FFPE bladder cancer tissue, arguing against the etiological role of HPV in non-muscle urothelial carcinogenesis.

  15. Tamoxifen Forms DNA Adducts In Human Colon After Administration Of A Single [14C]-Labeled Therapeutic Dose.

    Energy Technology Data Exchange (ETDEWEB)

    Brown, K; Tompkins, E M; Boocock, D J; Martin, E A; Farmer, P B; Turteltaub, K W; Ubick, E; Hemingway, D; Horner-Glister, E; White, I H

    2007-05-23

    Tamoxifen is widely prescribed for the treatment of breast cancer and is also licensed in the U.S. for the prevention of this disease. However, tamoxifen therapy is associated with an increased occurrence of endometrial cancer in women and there is also evidence that it may elevate the risk of colorectal cancer. The underlying mechanisms responsible for tamoxifen-induced carcinogenesis in women have not yet been elucidated but much interest has focussed on the role of DNA adduct formation. We investigated the propensity of tamoxifen to bind irreversibly to colorectal DNA when given to ten women as a single [{sup 14}C]-labeled therapeutic (20 mg) dose, {approx}18 h prior to undergoing colon resections. Using the sensitive technique of accelerator mass spectrometry, coupled with HPLC separation of enzymatically digested DNA, a peak corresponding to authentic dG-N{sup 2}-tamoxifen adduct was detected in samples from three patients, at levels ranging from 1-7 adducts/10{sup 9} nucleotides. No [{sup 14}C]-radiolabel associated with tamoxifen or its major metabolites was detected. The presence of detectable CYP3A4 protein in all colon samples suggests this tissue has the potential to activate tamoxifen to {alpha}-hydroxytamoxifen, in addition to that occurring in the systemic circulation, and direct interaction of this metabolite with DNA could account for the binding observed. Although the level of tamoxifeninduced damage displayed a degree of inter-individual variability, when present it was {approx}10-100 times higher than that reported for other suspect human colon carcinogens such as PhIP. These findings provide a mechanistic basis through which tamoxifen could increase the incidence of colon cancers in women.

  16. Prevalence and multiplicity of HPV in HIV women in Minas Gerais, Brazil Prevalência e multiplicidade do HPV em mulheres infectadas pelo HIV em Minas Gerais

    Directory of Open Access Journals (Sweden)

    Christine Miranda Corrêa

    2011-08-01

    Full Text Available OBJECTIVE: To detect the frequency and subtypes of HPV in the uterine cervix of HIV-infected women. METHODS: Sample consisted of 288 HIV-infected women, recruited from the public health system of five cities of Minas Gerais, Brazil. Women were seen from August 2003 to August 2008. Cervical samples were collected for cytological analysis and for HPV DNA detection, using polymerase chain reaction (PCR. HPV DNA was classified according to its oncogenic potential in low risk (types 6, 11 and high risk (types 16, 18, 31, 33, 35. Colposcopy was performed, followed by cervical biopsy when necessary. Categorical variables were compared using the Chi-squared test, with a significance level established at the 5% level. RESULTS: HPV prevalence was 78.8%. Most frequent genotypes were HPV-6 (63.9% and HPV-16 (48.5%. High-risk HPV were observed in 70.5% of the women; low-risk in 71.4%; both high and low-risk HPV were detected in 55.1% of the patients. Multiple HPV genotypes were detected in 64.8% of the patients; two genotypes in 23.8%, and three in 18.9%. CONCLUSION: HPV prevalence was high among HIV-infected women. Multiple HPV genotypes were common in samples from the uterine cervix of HIV-infected womenOBJETIVO: Detectar a frequência e os subtipos do HPV na cérvice uterina de mulheres infectadas pelo HIV. MÉTODOS: A amostra era composta por 288 mulheres infectadas pelo HIV, recrutadas do sistema público de saúde de cinco cidades de Minas Gerais, Brasil. As mulheres foram avaliadas de agosto de 2003 a agosto de 2008. Amostras cervicais foram coletadas para análise citológica e para detecção do HPV DNA, usando a reação em cadeia de polimerase (PCR. O HPV DNA foi classificado de acordo com seu potencial oncogênico em baixo risco (tipos 6,11 e alto risco (tipos 16, 18, 31, 33, 35. Foi realizada colposcopia, seguida de biópsia cervical, quando indicada. Variáveis categóricas foram comparadas usando o teste do quiquadrado, com nível de signific

  17. HPV DNA testing improves CIN2+ risk stratification and detection of CIN2+ in delayed triage of ASCUS and LSIL. A population-based follow-up study from Western Norway

    Science.gov (United States)

    Budal, Elisabeth B; Haugland, Hans K; Skar, Robert; Mæhle, Bjørn O; Bjørge, Tone; Vintermyr, Olav K

    2014-01-01

    In Norway, Pap smears with atypical squamous cells of uncertain significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are triaged after 6 months. The aim of the study was to evaluate effects of implementing human papillomavirus (HPV) test (2005) in delayed triage of ASCUS and LSIL in a cohort of women from Western Norway. After a survey of 119,469 cervical Pap smears during 2005–2007, a total of 1055 women with an index ASCUS or LSIL were included in the study and followed up for 3–6 years with respect to progression into cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Overall sensitivity for detection of CIN2+ with HPV testing and cytology was 96% and 72%, respectively. The sensitivity for detection of CIN2+ was not affected by age, but the specificity of the HPV test increased with age. Thus, for the age groups 50 years, the specificity of a positive HPV test to detect CIN2+ was 47%, 71%, and 82%, respectively. Positive predictive values for CIN2+ in women with positive cytology, positive HPV test, negative cytology, negative HPV test, or negative HPV and cytology tests were 52%, 41%, 8%, 1.5%, and 0.4%, respectively. HPV testing resulted in a net 22% increased detection of CIN2+. Fifty-six percent of CIN2+ was detected at an earlier time point with HPV testing in triage. Implementation of HPV testing in delayed triage of ASCUS and LSIL improved the stratification of CIN2+ risk and increased CIN2+ detection and at an earlier time point than with triage by cytology alone. PMID:24403090

  18. High prevalence of high-risk HPV genotypes other than 16 and 18 in cervical cancers of Curaçao: implications for choice of prophylactic HPV vaccine.

    Science.gov (United States)

    Hooi, Desiree J; Lissenberg-Witte, Birgit I; de Koning, Maurits N C; Pinedo, Herbert M; Kenter, Gemma G; Meijer, Chris J L M; Quint, Wim G

    2017-10-11

    Curaçao is a Dutch-Caribbean Island located in a high-risk area for cervical cancer.Prior to introduction of a prophylactic human papillomavirus (HPV) vaccine, knowledge of the prevalence of high-risk HPV vaccine genotypes (HPV16, 18, 31, 33, 45, 52 and 58) in cervical (pre)cancer is required. To investigate the prevalence of HPV genotypes in invasive cervical cancers (ICC) and cervical intraepithelial neoplasia (CIN) grade 1, 2 and 3 in Curaçao. Paraffin-embedded blocks of 104 cervical cancers (89 squamous, 15 adenocarcinoma), 41 CIN3, 39 CIN2 and 40 CIN1 lesions were analysed for the presence of HPV. Sections were stained by H&E for histopathological evaluation, and DNA was extracted using proteinase K. HPV genotypes were detected using Short PCR Fragment (SPF10) PCR DNA enzyme immunoassay and a Line Probe Assay (LiPA25) . HPV was found in 92 (88.5%) ICC; 87 (94.6%) had a single HPV infection and 86 (93.5%) were high-risk human papillomavirus (hrHPV)-type positive.The three most common HPV types in ICC were 16 (38.5%), 18 (13.5%) and 45 (6.7%), covering 58.7%.HrHPV vaccine genotypes 16, 18, 31, 35, 45, 52 and 58 were responsible for 73.1% of ICC. For precancerous lesions, the HPV attribution was 85.4% for CIN3, 66.7% for CIN2% and 42.5% for CIN1. Our study, the largest in the Caribbean region in (pre)cancer, shows that the prevalence of HPV-type 16 and 18 in cervical cancer is lower compared with the world population but no differences in prevalence of these two HPV types are seen in precancerous lesions.When considering HPV vaccination in Curaçao, the relatively high contribution of non-HPV 16/18 genotypes in ICC should be taken into account. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  19. Population-based evaluation of type-specific HPV prevalence among women in British Columbia, Canada.

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    Ogilvie, G S; Cook, D A; Taylor, D L; Rank, C; Kan, L; Yu, A; Mei, W; van Niekerk, D J; Coldman, A J; Krajden, M

    2013-02-04

    British Columbia (BC) introduced a school-based HPV vaccine program in September 2008. As part of the HPV vaccine program evaluation, we determined the type-specific HPV prevalence in a population-based sample of women presenting for routine cervical cancer screening in the province. From June 2010 to February 2011, a total of 1100 physicians from all health regions in BC were invited to return ten sequential cytobrushes used during routine office-based Pap screening to the Provincial Health Services Authority Laboratories for HPV type-specific testing. Client age was the only identifier provided. Specimens were screened by the Digene Hybrid Capture(®) 2 High-Risk (hr) HPV DNA Test (HC2). HC2 positive specimens were then genotyped using the Roche cobas(®) 4800 HPV Test, the Roche Linear Array (LA) HPV Genotyping Test and the Digene(®) HPV Genotyping LQ Test. Overall, 12.2% of the 4330 specimens with valid HC2 results were hrHPV positive. Age range was 15-69 (median 39.0). By age group, the proportion HC2 hrHPV positive was: 15-19, 25.7%; 20-24, 33.2%; 25-29, 21.9%; 30-34, 12.6%; 35-39, 9.5%; 40-44, 8.4%; ≥45, 3.4%. Overall hrHPV prevalence was 10.1% by Roche cobas(®) 4800, 10.5% by Roche LA and 10.3% by Digene LQ. For HPV 16/18, rates by age group by Roche LA were: 15-19, 5.1%/2.8%; 20-24, 9.5%/3.9%; 25-29, 6.2%/1.0%; 30-34, 2.4%/1.7%; 35-39, 1.2%/1.0%; 40-44, 1.6%/0.2%; ≥45, 0.3%/0.2%. Similar HPV 16/18 rates were obtained with the Digene LQ and Roche cobas(®) 4800 methods. Agreement between the three genotyping methods for HPV 16 and 18 was high. Comparable to other evaluations, hrHPV positivity was highest among younger women and HPV 16 was the most frequent genotype detected. These baseline estimates will be useful for monitoring the effectiveness of the HPV vaccine in BC. Type-specific analyses repeated at regular intervals over time may determine whether the use of HPV vaccine results in hrHPV genotype replacement in the province. Copyright © 2012

  20. HPV types, HIV and invasive cervical carcinoma risk in Kampala, Uganda: a case-control study

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    Kleter Bernhard

    2011-06-01

    Full Text Available Abstract Background While the association of human papillomavirus (HPV with cervical cancer is well established, the influence of HIV on the risk of this disease in sub-Saharan Africa remains unclear. To assess the risk of invasive cervical carcinoma (ICC associated with HIV and HPV types, a hospital-based case-control study was performed between September 2004 and December 2006 in Kampala, Uganda. Incident cases of histologically-confirmed ICC (N=316 and control women (N=314, who were visitors or care-takers of ICC cases in the hospital, were recruited. Blood samples were obtained for HIV serology and CD4 count, as well as cervical samples for HPV testing. HPV DNA detection and genotyping was performed using the SPF10/DEIA/LiPA25 technique which detects all mucosal HPV types by DEIA and identifies 25 HPV genotypes by LiPA version 1. Samples that tested positive but could not be genotyped were designated HPVX. Odds ratios (OR and 95% confidence intervals (CI were calculated by logistic regression, adjusting for possible confounding factors. Results For both squamous cell carcinoma (SCC and adenocarcinoma of the cervix, statistically significantly increased ORs were found among women infected with HPV, in particular single HPV infections, infections with HPV16-related types and high-risk HPV types, in particular HPV16, 18 and 45. For other HPV types the ORs for both SCC and adenocarcinoma were not statistically significantly elevated. HIV infection and CD4 count were not associated with SCC or adenocarcinoma risk in our study population. Among women infected with high-risk HPV types, no association between HIV and SCC emerged. However, an inverse association with adenocarcinoma was observed, while decrease in CD4 count was not associated with ICC risk. Conclusions The ORs for SCC and adenocarcinoma were increased in women infected with HPV, in particular single HPV infections, infections with HPV16- and 18-related types, and high-risk HPV types

  1. Spectrum of HPV types before and after treatment of cervical intraepithelial neoplasia grade 2 and 3.

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    Lindroth, Ylva; Bjelkenkrantz, Kaj; Forslund, Ola

    2017-10-31

    To monitor residual disease after treatment of high grade cervical intraepithelial neoplasia (CIN), cytology together with human papillomavirus (HPV) testing are commonly performed. To analyse the spectrum of HPV types before and after treatment. This register-based study included 446 women treated for CIN2 or 3, where cytology samples had been HPV-tested before and after treatment by the use of the MGP-PCR Luminex HPV L1-DNA-assay identifying 39 HPV types, including 12 high risk (HR) HPV types. Before and after treatment, 706 and 248 HPV isolates were detected of 36 and 34 different HPV types, respectively. Among all the HR HPV isolates, type-specific persistency was observed among 14% (76/542) after treatment, compared to 34% (31/92) of low-risk (LR) HPV isolates (pHPV isolates, 8.3% (6/72) persisted. Totally, 99% (440/446) and 40% (179/446) of the women were HPV-positive before and after treatment, respectively. At least one of the 12 HR HPV types was present in 91% (404/446) and 24% (109/446) of the women before and after treatment, respectively (pHPV types were present both before and after treatment among 23% (102/446) of the women, and 16% (71/446) manifested at least one persistent HR HPV type. The sensitivity, specificity and negative predictive value of HR HPV testing for detection of residual high grade squamous intraepithelial lesion (HSIL) was based on the first cytology after treatment, and was 91.7% (95% CI: 61.5%-99.8%), 84.1% (95% CI: 80.0%-87.7%) and 99.7% (95% CI: 98.2%-100.0%), respectively. About one out six treated women (16%) manifested at least one persistent HR HPV type, that was associated with recurrent or residual HSIL disease (odds ratio 58.1, 95% CI 7.4-457) (p=0.0001). Testing for HR HPV demonstrated high sensitivity (92%) for residual HSIL. The higher persistency rate of LR HPV types suggests that they are more likely to be outside the treated area. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Persistent Oral Human Papillomavirus (HPV) Infection is Associated with Low Salivary Levels of Matrix Metalloproteinase 8 (MMP-8).

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    Haukioja, Anna; Tervahartiala, Taina; Sorsa, Timo; Syrjänen, Stina

    2017-10-23

    A persistent human papillomavirus (HPV) infection is a prerequisite for a HPV related cancer to develop. Asymptomatic, persistent HPV infections are not only found in genital tract, but also on oral mucosa. Oral HPV persistence may be associated with behavioural factors, but data on the role of innate immunity in oral HPV infections are still limited. Salivary concentrations of matrix metalloproteinases MMP-8 and MMP-9, tissue inhibitor of MMPs (TIMP-1), myeloperoxidase, and serum concentrations of MMP-8 were analysed in women with a persistent oral HPV infection and, as a control, in women who remained HPV DNA-negative during a 6-year follow-up. The effects of smoking, lactation and alcohol use on the salivary and serum parameters were assessed, too. A nested case-control setting was used to select a subgroup of 57 women with a persistent oral HPV infection and 102 controls from the Finnish Family HPV Study. The salivary MMP-8/TIMP-1 molar ratio was lower in HPV DNA-positive women than in controls (p=0.036). The difference was more pronounced in non-smoking women, in this group also the salivary MMP-8 levels differed (p=0.047). There was a correlation between the salivary concentrations of myeloperoxidase and MMP-8 (r=0.567, pHPV infection was associated with a low salivary MMP-8 concentration indicating eventually a failure in oral anti-inflammatory defence. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Targeting DNA Replication and Repair for the Development of Novel Therapeutics against Tuberculosis

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    Michael A. Reiche

    2017-11-01

    Full Text Available Mycobacterium tuberculosis is the etiological agent of tuberculosis (TB, an infectious disease which results in approximately 10 million incident cases and 1.4 million deaths globally each year, making it the leading cause of mortality from infection. An effective frontline combination chemotherapy exists for TB; however, this regimen requires the administration of four drugs in a 2 month long intensive phase followed by a continuation phase of a further 4 months with two of the original drugs, and is only effective for the treatment of drug-sensitive TB. The emergence and global spread of multidrug-resistant (MDR as well as extensively drug-resistant (XDR strains of M. tuberculosis, and the complications posed by co-infection with the human immunodeficiency virus (HIV and other co-morbidities such as diabetes, have prompted urgent efforts to develop shorter regimens comprising new compounds with novel mechanisms of action. This demands that researchers re-visit cellular pathways and functions that are essential to M. tuberculosis survival and replication in the host but which are inadequately represented amongst the targets of current anti-mycobacterial agents. Here, we consider the DNA replication and repair machinery as a source of new targets for anti-TB drug development. Like most bacteria, M. tuberculosis encodes a complex array of proteins which ensure faithful and accurate replication and repair of the chromosomal DNA. Many of these are essential; so, too, are enzymes in the ancillary pathways of nucleotide biosynthesis, salvage, and re-cycling, suggesting the potential to inhibit replication and repair functions at multiple stages. To this end, we provide an update on the state of chemotherapeutic inhibition of DNA synthesis and related pathways in M. tuberculosis. Given the established links between genotoxicity and mutagenesis, we also consider the potential implications of targeting DNA metabolic pathways implicated in the

  4. Comparison of human papillomavirus detection by Aptima HPV and cobas HPV tests in a population of women referred for colposcopy following detection of atypical squamous cells of undetermined significance by Pap cytology.

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    Castle, Philip E; Eaton, Barbara; Reid, Jennifer; Getman, Damon; Dockter, Janel

    2015-04-01

    Few studies have compared the cobas HPV test to the Aptima HPV assay (AHPV) and the Aptima HPV 16 18/45 genotype assay (AHPV GT) for high-risk human papillomavirus (hrHPV) detection, clinical performance in detecting cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+) diagnoses, and risk stratification by partial HPV genotyping. The cobas HPV test is a DNA test that separately and concurrently detects HPV16, HPV18, and a pool of 12 other hrHPV types. AHPV is an RNA test for a pool of 14 hrHPV genotypes, and AHPV GT is an RNA test run on AHPV-positive results to detect HPV16 separately from HPV18 and HPV45, which are detected together. In a population of patients (n=988) referred for colposcopy because of a cervical Pap cytology result of atypical squamous cells of undetermined significance (ASC-US), a cervical scrape specimen was taken, placed into a ThinPrep Pap test vial containing PreservCyt liquid cytology medium, and tested in a blinded fashion with cobas and AHPV and with AHPV GT for AHPV-positive results. The final diagnoses were based on a consensus panel review of the biopsy specimen histology. AHPV and cobas were equally sensitive for CIN2+ diagnoses (89.4% each; P=1.000), and AHPV was more specific than cobas (63.1% versus 59.3%; P≤0.001). The percent total agreement, percent positive agreement, and kappa value were 90.9%, 81.1%, and 0.815, respectively. Risk stratification using partial HPV genotyping was similar for the two assays. AHPV and AHPV GT had similar sensitivity and risk stratification to cobas HPV, but they were more specific than cobas HPV. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  5. High incidence of oncogenic HPV genotypes found in women from Southern Brazil

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    Ludmila G Entiauspe

    2014-06-01

    Full Text Available Oncogenic HPV genotypes are strongly associated with premalignant and malignant cervical lesion. The purpose was to determine human papillomavirus (HPV prevalence and genotypes, and to estimate cervical cancer risk factor associations. Cervical samples were obtained from 251 women seeking gynecological care at the Pelotas School of Medicine Clinic. This is a cross-sectional study. HPV-DNA was amplified by nested-PCR using MY09/11 and GP5/6 primers, and the sequencing was used for genotyping. Sociodemographic and behavioral risk factors were obtained by closed questionnaire, and its relationship to HPV infection prevalence were analyzed. Statistical analyses were performed using SPSS 16.0 software, and differences were considered significant at p < 0.05. As results, the prevalence of HPV infection was 29.9%. The most frequent genotype was HPV-16 (41.3%, followed by HPV-18 (17.3%, and HPV-33 (9.3%. Others nine HPV genotypes were also found. On this population, prevalence of oncogenic HPV genotypes was high, but does not seem to confer relationship with the risk factors investigated. Future investigations in larger populations are necessary, for the proposition of more appropriated monitoring strategies and treatment according to the Brazilian health service reality, as well as patients.

  6. High incidence of oncogenic HPV genotypes found in women from Southern Brazil.

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    Entiauspe, Ludmila G; Silveira, Mariângela; Nunes, Emily M; Basgalupp, Suélen P; Stauffert, Dulce; Dellagostin, Odir A; Collares, Tiago; Seixas, Fabiana K

    2014-01-01

    Oncogenic HPV genotypes are strongly associated with premalignant and malignant cervical lesion. The purpose was to determine human papillomavirus (HPV) prevalence and genotypes, and to estimate cervical cancer risk factor associations. Cervical samples were obtained from 251 women seeking gynecological care at the Pelotas School of Medicine Clinic. This is a cross-sectional study. HPV-DNA was amplified by nested-PCR using MY09/11 and GP5/6 primers, and the sequencing was used for genotyping. Sociodemographic and behavioral risk factors were obtained by closed questionnaire, and its relationship to HPV infection prevalence were analyzed. Statistical analyses were performed using SPSS 16.0 software, and differences were considered significant at p HPV infection was 29.9%. The most frequent genotype was HPV-16 (41.3%), followed by HPV-18 (17.3%), and HPV-33 (9.3%). Others nine HPV genotypes were also found. On this population, prevalence of oncogenic HPV genotypes was high, but does not seem to confer relationship with the risk factors investigated. Future investigations in larger populations are necessary, for the proposition of more appropriated monitoring strategies and treatment according to the Brazilian health service reality, as well as patients.

  7. HPV Prevalence in Colombian Women with Cervical Cancer: Implications for Vaccination in a Developing Country

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    Raúl Murillo

    2009-01-01

    Full Text Available Human Papillomavirus (HPV vaccines have been considered potentially cost-effective for the reduction of cervical cancer burden in developing countries; their effectiveness in a public health setting continues to be researched. We conducted an HPV prevalence survey among Colombian women with invasive cancer. Paraffin-embedded biopsies were obtained from one high-risk and one low-middle-risk regions. GP5+/GP6+ L1 primers, RLB assays, and E7 type specific PCR were used for HPV-DNA detection. 217 cases were analyzed with 97.7% HPV detection rate. HPV-16/18 prevalence was 63.1%; HPV-18 had lower occurrence in the high-risk population (13.8% versus 9.6% allowing for the participation of less common HPV types; HPV-45 was present mainly in women under 50 and age-specific HPV type prevalence revealed significant differences. Multiple high-risk infections appeared in 16.6% of cases and represent a chance of replacement. Age-specific HPV prevalence and multiple high-risk infections might influence vaccine impact. Both factors highlight the role of HPVs other than 16/18, which should be considered in cost-effectiveness analyses for potential vaccine impact.

  8. Detection of E6/E7 HPV oncogene transcripts as biomarker of cervical intaepithelial displasia

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    Mauro Carcheri

    2009-09-01

    Full Text Available It is widely accepted that only persistent infection with high risk types of Human Papillomavirus (HPV HR is a significant risk factor for the development of an invasive squamous cervical cancer. The overexpression of viral oncogenes E6/E7 of HPV is considered a necessary process for incurring in a malignant phenotype.A HPV infection can be identified by detection of HPV DNA in biological samples, but the DNAbased tests cannot delineate between transient or persistent and potentially transforming infection. Instead there is many evidence to suggest that detection of HPV gene expression may constitute a more specific approach to highlight a clinically significant infection. Especially seems that the detection of E6/E7 transcripts can be usefully used for identify the women with a persistent HPV infection that will can induce a future cervical cancer. The aim of our study is to investigate if the detection of oncogenic viral gene activity by detecting transcripts of the E6 and E7 genes can be most usefull of HPV-DNA test in the triage of ASCUS or low grade cervical lesions. Our results confirm that HPV E6/E7 mRNA test can be considered a promising method to stratify HPV positive women for risk of future high-grade cervical lesions or cervical intaepithelial neoplasia.

  9. Anal Squamous Intraepithelial Lesions and HPV Among Young Black Men Who Have Sex with Men.

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    Keglovitz, Kristin; Richardson, Andrew D; Lancki, Nicola; Walsh, Tim; Schneider, John A

    2017-02-01

    Limited data are available on anal squamous intraepithelial lesions (ASILs) and anal human papillomavirus (HPV) infection in young, Black populations. The purpose of this study was to examine the prevalence of and relationships between ASILs and high-risk HPV infection in a young (<30 years of age), predominantly Black, men who have sex with men (MSM) population. Results of anal cytology and HPV DNA were gathered for 83 individuals. Forty-two percent of individuals (35) had atypical squamous cells of undetermined significance and 33% (27) had low-grade squamous intraepithelial lesion by cytology. Only 9% tested positive for both high-risk HPV subtypes 16 and 18. Low rates of infection with both HPV types 16 and 18 may provide further evidence that we should continue to vaccinate young, Black MSM against HPV.

  10. Impact of HPV infection on the development of head and neck cancer

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    Betiol, J.; Villa, L.L.; Sichero, L.

    2013-01-01

    Human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) is considered to be a distinct clinical entity with better prognosis than the classical tobacco- and alcohol-associated tumors. The increasing incidence of this neoplasia during the last decades highlights the need to better understand the role of HPV in the development of these cancers. Although the proportion of HNSCC attributed to HPV varies considerably according to anatomical site, overall approximately 25% of all HNSCC are HPV-DNA positive, and HPV-16 is by far the most prevalent type. In this review we discuss the existing evidence for a causal association between HPV infection and HNSCC at diverse anatomical head and neck subsites. PMID:23532264

  11. Circumcision and Sexual Behavior: Factors Independently Associated with Human Papillomavirus (HPV) Detection among Men in The HIM Study

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    Giuliano, AR; Lazcano, E; Villa, LL; Flores, R; Salmeron, J; Lee, J-H; Papenfuss, M; Abrahamsen, M; Baggio, ML; Silva, R; Quiterio, M

    2012-01-01

    There is growing interest in understanding HPV infection and related disease among men. To date there have been numerous studies reporting HPV DNA prevalence among men from several different countries, however, few have incorporated multivariable analyses to determine factors independently associated with male HPV detection. The purpose of this study was to assess the factors independently associated with HPV detection in men ages 18–70 years residing in Brazil (n=343), Mexico (n=312), and the United States (US) (n=333). In samples combined from the coronal sulcus, glans penis, shaft, and scrotum we evaluated factors associated with any, oncogenic, and non-oncogenic HPV infections. In multivariable analyses, detection of any HPV infection was significantly associated with reported race of Asian/Pacific Islander, lifetime and recent number of sexual partners, and having sex in the past three months. Oncogenic HPV detection was independently associated with lifetime and recent number of sexual partners, and having sex in the past three months. Non-Oncogenic HPV infection was independently associated with lifetime number of sexual partners. Circumcision, assessed by clinical examination, was associated with reduced risk of HPV detection across all categories of HPV evaluated. HPV detection in men in the current study was strongly related to sexual behavior and circumcision status. Interventions such as circumcision may provide a low cost method to reduce HPV infection. PMID:19089913

  12. High prevalence of genital HPV infection among long-term monogamous partners of women with cervical dysplasia or genital warts-Another reason for HPV vaccination of boys.

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    Rob, Filip; Tachezy, Ruth; Pichlík, Tomáš; Rob, Lukáš; Kružicová, Zuzana; Hamšíková, Eva; Šmahelová, Jana; Hercogová, Jana

    2017-01-01

    We conducted a cross-sectional study on the occurrence of a specific type of genital human papillomavirus (HPV) among long-term monogamous male partners of women with cervical dysplasia and genital warts. The purpose of the study was to improve knowledge with regards to the management of these couples. The presence of genital HPV-DNA was detected by PCR with broad spectrum primers followed by hybridization. 82 males met the study criteria, 41 in each group. Genital HPV-DNA prevalence was 67.5% in the genital warts group and 72.2% in the cervical dysplasia group. The prevalence of high risk HPVs was higher in the cervical dysplasia group, while low risk HPVs were more prevalent in the genital warts group (p < .05). The prevalence of HPV in males was independent of the duration of the relationship (73.5% for 6-24 months and 66.7% for longer relationships). In conclusion, our results suggest that the prevalence of the genital HPV infection in both groups of male partners is comparable and very high, but the spectrum of HPV types varies significantly. The presence of the genital HPV infection in male sexual partners seems to be independent of the duration of the relationship. Applying the HPV vaccination to boys may prevent this phenomenon. © 2016 Wiley Periodicals, Inc.

  13. Human Papillomavirus (HPV in breast tumors: prevalence in a group of Mexican patients

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    Cetina Lucely

    2009-01-01

    Full Text Available Abstract Background Breast cancer is one of the main health problems in developed countries, occupying first place in mortality in women. It is well-known that there are risk factors associated with breast cancer development. Nonetheless, in 50–80% of cases known risk factors have not been identified, this has generated the attempt to identify new factors related with this neoplasia as viral infections. The aim of this work is investigate the prevalence of HPV DNA in patients with breast lesions at the Instituto Nacional de Cancerologia de Mexico. Methods Fifty-one cases of breast cancer were selected from the files of the institute and compared by age and tumor size with 43 cases of non malignant breast lesions (fibroadenoma, fibrocystic disease and phyllodes tumor. Paraffin embedded specimens were selected, HPV DNA was analyzed by polymerase chain reaction (PCR and sequenced for different types of HPV in case of positivity for HPV-DNA. Descriptive analysis of clinical and pathological variables was performed and comparisons between positive and negative cases was done. Results All patients were mexican, mean age was 53.3, median age of menarche was 13 and median tumor size 9 cms. Cervicovaginal cytology was performed to all patients, 1 patient (1.9% of cancer group had HPV and none in the other group, no cases were diagnosed with cervical dysplasia. In the group of carcinomas 36 (70.5% were negative and 15 (29.4% were positive to HPV-DNA, 10(66.6% were positive for HPV 16, 3(20% for HPV 18, two cases (13.4% were positive for both. In the group of benign conditions all were negative to HPV-DNA. Conclusion Presence of HPV in breast cancer in our group of cases is high in comparison to other authors; larger numbers of cases need to be analyzed in order to establish the exact role of this virus in the pathogenesis of breast cancer.

  14. HPV16E6-Dependent c-Fos Expression Contributes to AP-1 Complex Formation in SiHa Cells

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    Feixin Liang

    2011-01-01

    Full Text Available To date, the major role of HPV16E6 in cancer has been considered to be its ability to inhibit the p53 tumor-suppressor protein, thereby thwarting p53-mediated cytotoxic responses to cellular stress signals. Here, we show that HPV16E6-dependent c-fos oncogenic protein expression contributes to AP-1 complex formation under oxidative stress in SiHa cells (HPV16-positive squamous cell carcinoma of the cervix. In addition, we examined the role of HPV16E6 in TGF-α-induced c-fos expression and found that the c-fos protein expression induced by TGF-α is HPV16E6 dependent. Thus, our results provide the first evidence that HPV16E6 contributes to AP-1 complex formation after both ligand-dependent and independent EGFR activation, suggesting a new therapeutic approach to the treatment of HPV-associated tumors.

  15. Detection of HPV16 in Esophageal Cancer in a High-Incidence Region of Malawi

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    Anja Lidwina Geßner

    2018-02-01

    Full Text Available This study was designed to explore the role of human papillomavirus (HPV in esophageal squamous cell carcinoma (ESCC. Fifty-five patients receiving diagnostic upper gastrointestinal endoscopy at Zomba Central Hospital or Queen Elizabeth Hospital in Blantyre (Malawi in 2010, were included in our study. Formalin-fixed paraffin-embedded biopsies were collected for histopathological diagnosis. HPV DNA was detected using multiplex Quantitative PCR (qPCR and in situ hybridization (ISH. p16INK4a staining served as a surrogate marker for HPV oncogene activity. Cell proliferation was determined by Ki-67 staining. Human immunodeficiency virus (HIV status was evaluated by serology. Data on the consumption of alcohol and tobacco, and history of tuberculosis (TBC, oral thrush, and Herpes zoster, were obtained by questionnaire. Forty patients displayed ESCC, three displayed dysplastic epithelium, and 12 displayed normal epithelium. HPV16 was detected in six ESCC specimens and in one dysplastic lesion. Among HPV-positive patients, viral load varied from 0.001 to 2.5 copies per tumor cell. HPV DNA presence could not be confirmed by ISH. p16INK4a positivity correlated with the presence of HPV DNA (p = 0.03. Of particular note is that the Ki-67 proliferation index, in areas with diffuse nuclear or cytoplasmatic p16INK4a staining ≥50%, was significantly higher in HPV-positive tumors compared to the corresponding p16INK4a stained areas of HPV-negative tumors (p = 0.004. HPV infection in ESCC was not associated with the consumption of tobacco or alcohol, but there were significantly more patients drinking locally brewed alcohol among HPV-positive tumor patients compared to non-tumor patients (p = 0.02 and compared to HPV-negative tumor patients (p = 0.047. There was no association between HIV infection, history of TBC, Herpes zoster, oral thrush, or HPV infection, in ESCC patients. Our indirect evidence for viral oncogene activity is restricted to single tumor

  16. Genotyping for Human Papillomavirus (HPV 16/18/52/58 Has a Higher Performance than HPV16/18 Genotyping in Triaging Women with Positive High-risk HPV Test in Northern Thailand.

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    Surapan Khunamornpong

    Full Text Available Testing for high-risk human papillomavirus DNA (HPV test has gained increasing acceptance as an alternative method to cytology in cervical cancer screening. Compared to cytology, HPV test has a higher sensitivity for the detection of histologic high-grade squamous intraepithelial lesion or worse (HSIL+, but this could lead to a large colposcopy burden. Genotyping for HPV16/18 has been recommended in triaging HPV-positive women. This study was aimed to evaluate the screening performance of HPV testing and the role of genotyping triage in Northern Thailand.A population-based cervical screening program was performed in Chiang Mai (Northern Thailand using cytology (conventional Pap test and HPV test (Hybrid Capture 2. Women who had abnormal cytology or were HPV-positive were referred for colposcopy. Cervical samples from these women were genotyped using the Linear Array assay.Of 5,456 women, 2.0% had abnormal Pap test results and 6.5% tested positive with Hybrid Capture 2. Of 5,433 women eligible for analysis, 355 with any positive test had histologic confirmation and 57 of these had histologic HSIL+. The sensitivity for histologic HSIL+ detection was 64.9% for Pap test and 100% for Hybrid Capture 2, but the ratio of colposcopy per detection of each HSIL+ was more than two-fold higher with Hybrid Capture 2 than Pap test (5.9 versus 2.8. Genotyping results were available in 316 samples. HPV52, HPV16, and HPV58 were the three most common genotypes among women with histologic HSIL+. Performance of genotyping triage using HPV16/18/52/58 was superior to that of HPV16/18, with a higher sensitivity (85.7% versus 28.6% and negative predictive value (94.2% versus 83.9%.In Northern Thailand, HPV testing with genotyping triage shows better screening performance than cervical cytology alone. In this region, the addition of genotyping for HPV52/58 to HPV16/18 is deemed necessary in triaging women with positive HPV test.

  17. Association of Chlamydia trachomatis infection with human papillomavirus (HPV & cervical intraepithelial neoplasia - A pilot study

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    Neerja Bhatla

    2013-01-01

    Methods: A total of 600 consecutively selected women aged 30-74 yr with persistent vaginal discharge, intermenstrual/postcoital bleeding or unhealthy cervix underwent conventional Pap smear, Hybrid Capture 2® (HC2 testing for HPV and CT DNA and colposcopy, with directed biopsy of all lesions. Results: HPV DNA was positive in 108 (18.0% women, CT DNA in 29 (4.8% women. HPV/CT co-infection was observed in only four (0.7% women. Of the 127 (21.2% women with Pap >ASCUS, 60 (47.2% were HPV positive and four (3.1% were CT positive. Of the 41 women with CIN1 lesions, 11 (26.8% were HPV positive, while two were CT positive. Of the 46 women with CIN2+ on histopathology, 41 (89.1% were HPV positive, two (4.3% were CT positive and one was positive for both. The risk of CIN2+ disease was significantly increased (P35 yr, higher parity, use of oral contraceptives or smoking did not show any significant association with HPV or abnormal histopathology. Parity >5 was the only risk factor positivity associated with CT infection (P<0.05. Interpretation & conclusions: Our findings showed that CT infection was not significantly associated with CIN, and most of its risk factors, including HPV infection, in symptomatic women. Longitudinal studies with carefully selected study sample would be able to answer these questions.

  18. A novel self-assembled nanoparticle vaccine with HIV-1 Tat₄₉₋₅₇/HPV16 E7₄₉₋₅₇ fusion peptide and GM-CSF DNA elicits potent and prolonged CD8⁺ T cell-dependent anti-tumor immunity in mice.

    Science.gov (United States)

    Tang, Jun; Yin, Rui; Tian, Yi; Huang, Zeming; Shi, Jinglei; Fu, Xiaolan; Wang, Li; Wu, Yuzhang; Hao, Fei; Ni, Bing

    2012-02-01

    Peptide-based vaccines derived from the E7 protein of human papillomavirus (HPV) type 16 were developed to induce effective T cell responses against established cervical cancer, but have met with limited clinical success. It is necessary to develop novel peptide-based strategies to substantially improve the immune response against HPV16-related cancer. In this study, we aimed to design a novel peptide-based self-assembled nanoparticle HPV16 vaccine by combining the cell-penetrating peptide HIV-1 Tat(49-57) that was fused with the HPV16 E7(49-57) cytotoxic T lymphocyte (CTL) epitope and the granulocyte-macrophage colony stimulating factor (GM-CSF) gene, and to investigate how it improves the immune response and the therapeutic outcome ex vivo and in vivo. Nanoparticles were prepared and identified by transmission electron microscopy (TEM), gel retardation and DNase I protection assays. This type of vaccine formulation formed the 20-80 nm nanoparticles, and greatly improved epitope-specific immunity both ex vivo and in vivo. Importantly, this vaccine type was associated with decreased tumor growth and enhanced long-term survival in the prophylactic and therapeutic mouse models. The underlying mechanisms were determined to involve priming of enhanced frequency of CD8(+) memory T subtype cells. These results suggest that the nanoparticle Tat-E7/pGM-CSF represents a promising novel approach to enhance the potency of peptide-based cervical cancer vaccines, and this vaccine design strategy may act as a useful reference for research of virus-associated diseases and specific tumor immunotherapies. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. HPV Infections in Adolescents

    Directory of Open Access Journals (Sweden)

    Anna-Barbara Moscicki

    2007-01-01

    Full Text Available Adolescents who are sexually active have the highest rates of prevalent and incident HPV infection rates with over 50–80% having infections within 2–3 years of initiating intercourse. These high rates reflect sexual behavior and biologic vulnerability. Most infections are transient in nature and cause no cytologic abnormality. However, a small number of adolescents will not clear the infection. Persistence of HPV is strongly linked to the development of high-grade squamous intra-epithelial lesions (HSIL and invasive cancer. The HSIL detected, however, does not appear to progress rapidly to invasive cancer. Understanding the natural history of HPV in adolescents has shed light into optional treatment strategies which include watchful observation of atypical squamous cells of undetermined significance (ASCUS and low grade (LSIL. The association between age of first intercourse and invasive cancer cannot be ignored. Consequently, initiating screening at appropriate times in this vulnerable group is essential. In addition, with the advent of the HPV vaccine, vaccination prior to the onset of sexual activity is critical since most infections occur within a short time frame post initiation.

  20. HPV Vaccine and Pregnancy

    Science.gov (United States)

    ... breastfeeding. The father of the baby received the HPV vaccine around the time that I got pregnant. Is there a risk to the baby? No. There is no evidence that vaccines given to men will affect the sperm. In general, exposures that fathers have are unlikely ...

  1. HPV Testing Among Providers

    Centers for Disease Control (CDC) Podcasts

    2009-10-15

    Dr. Walter Kinney, a gynecologic oncologist with The Permanente Medical Group in Sacramento, California, talks about Pap and human papillomavirus (HPV) cotesting in women aged 30 and over.  Created: 10/15/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Cancer Prevention and Control (DCPC).   Date Released: 6/9/2010.

  2. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women.

    Science.gov (United States)

    Joura, Elmar A; Giuliano, Anna R; Iversen, Ole-Erik; Bouchard, Celine; Mao, Constance; Mehlsen, Jesper; Moreira, Edson D; Ngan, Yuen; Petersen, Lone Kjeld; Lazcano-Ponce, Eduardo; Pitisuttithum, Punnee; Restrepo, Jaime Alberto; Stuart, Gavin; Woelber, Linn; Yang, Yuh Cheng; Cuzick, Jack; Garland, Suzanne M; Huh, Warner; Kjaer, Susanne K; Bautista, Oliver M; Chan, Ivan S F; Chen, Joshua; Gesser, Richard; Moeller, Erin; Ritter, Michael; Vuocolo, Scott; Luxembourg, Alain

    2015-02-19

    The investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age. We performed a randomized, international, double-blind, phase 2b-3 study of the 9vHPV vaccine in 14,215 women. Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6. Serum was collected for analysis of antibody responses. Swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue were obtained and used for HPV DNA testing, and liquid-based cytologic testing (Papanicolaou testing) was performed regularly. Tissue obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and conization) was tested for HPV. The rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9vHPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1000 person-years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to HPV-31, 33, 45, 52, and 58 in a prespecified per-protocol efficacy population (susceptible population) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group (efficacy of the 9vHPV vaccine, 96.7%; 95% confidence interval, 80.9 to 99.8). Antibody responses to HPV-6, 11, 16, and 18 were noninferior to those generated by the qHPV vaccine. Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group. The 9vHPV vaccine prevented infection and disease

  3. Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery

    Science.gov (United States)

    Tian, Xi; Lara, Haydee; Wagner, Kyle T.; Saripalli, Srinivas; Hyder, Syed Nabeel; Foote, Michael; Sethi, Manish; Wang, Edina; Caster, Joseph M.; Zhang, Longzhen; Wang, Andrew Z.

    2015-11-01

    Radiotherapy is a key component of cancer treatment. Because of its importance, there has been high interest in developing agents and strategies to further improve the therapeutic index of radiotherapy. DNA double-strand repair inhibitors (DSBRIs) are among the most promising agents to improve radiotherapy. However, their clinical translation has been limited by their potential toxicity to normal tissue. Recent advances in nanomedicine offer an opportunity to overcome this limitation. In this study, we aim to demonstrate the proof of principle by developing and evaluating nanoparticle (NP) formulations of KU55933, a DSBRI. We engineered a NP formulation of KU55933 using nanoprecipitation method with different lipid polymer nanoparticle formulation. NP KU55933 using PLGA formulation has the best loading efficacy as well as prolonged drug release profile. We demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment.

  4. High-risk HPV is not associated with epithelial ovarian cancer in a Caucasian population

    DEFF Research Database (Denmark)

    Ingerslev, Kasper; Hogdall, Estrid; Skovrider-Ruminski, Wojciech

    2016-01-01

    BACKGROUND: High-risk human papillomavirus (HPV) has been suspected to play a role in the carcinogenesis of epithelial ovarian cancer (EOC). However, results from previous studies are conflicting. In most of these studies, the number of tissue samples was small. The current study was therefore...... undertaken to examine the prevalence of high-risk HPV DNA in EOC in a large series of patients. METHOD: Formalin-fixed, paraffin-imbedded tumor tissue samples from 198 cases consecutively included in the Danish Pelvic Mass Study were analyzed. The material included 163 serous adenocarcinomas, 15 endometrioid...... adenocarcinomas, 11 mucinous adenocarcinomas and nine clear-cell carcinomas. Genotyping for high-risk HPV DNA was performed by real-time Polymerase chain reaction (PCR) using an in-house TaqMan singleplex assay targeting the E6/E7 region of the HPV 16 and 18 genomes. Additionally, 20 random samples without HPV 16...

  5. High-risk HPV is not associated with epithelial ovarian cancer in a Caucasian population

    DEFF Research Database (Denmark)

    Ingerslev, Kasper; Hogdall, Estrid; Skovrider-Ruminski, Wojciech

    2016-01-01

    BACKGROUND: High-risk human papillomavirus (HPV) has been suspected to play a role in the carcinogenesis of epithelial ovarian cancer (EOC). However, results from previous studies are conflicting. In most of these studies, the number of tissue samples was small. The current study was therefore...... and/or 18 infections were reanalyzed for HPV subtypes 31, 33, 35, 39, 45, 51 and 52. RESULTS: The quality criteria were fulfilled in 191 samples. HPV 18 DNA was detected in one sample only, while the rest tested negative. The subgroup analysis for seven additional high-risk HPV subtypes was also...... undertaken to examine the prevalence of high-risk HPV DNA in EOC in a large series of patients. METHOD: Formalin-fixed, paraffin-imbedded tumor tissue samples from 198 cases consecutively included in the Danish Pelvic Mass Study were analyzed. The material included 163 serous adenocarcinomas, 15 endometrioid...

  6. Cervical, anal and oral HPV in an adolescent inner-city health clinic providing free vaccinations.

    Directory of Open Access Journals (Sweden)

    Nicolas F Schlecht

    Full Text Available Published human papillomavirus (HPV vaccine trials indicate efficacy is strongest for those naive to the vaccine-types. However, few high-risk young women have been followed and cervical HPV has been the predominant outcome measure.We collected cervical and anal swabs, as well as oral rinse specimens from 645 sexually active inner-city young females attending a large adolescent health-clinic in New York City that offers free care and HPV vaccination. Specimens were tested for HPV-DNA using a MY09/MY11-PCR system. Type-specific prevalence of HPV at each anatomic site was compared for individuals by vaccination dose using generalized estimating equation logistic regression models.The majority of subjects reported being of non-Caucasian (92% and/or Hispanic ethnicity (61%. Median age was 18 years (range:14-20. All had practiced vaginal sex, a third (33% practiced anal sex, and most (77% had also engaged in oral sex. At enrollment, 21% had not received the vaccine and 51% had received three doses. Prevalent HPV infection at enrollment was detected in 54% of cervical, 42% of anal and 20% of oral specimens, with vaccine types present in 7%, 6% and 1% of specimens, respectively. Comparing prevalence for vaccine types, the detection of HPV in the cervix of vaccinated compared to unvaccinated adolescents was significantly reduced: HPV6/11 (odds ratio [OR] = 0.19, 95%CI:0.06-0.75, HPV16 (OR = 0.31, 95%CI:0.11-0.88 and HPV18 (OR = 0.14, 95%CI:0.03-0.75. For anal HPV, the risk of detecting vaccine types HPV6/11 (OR = 0.27, 95%CI:0.10-0.72 and HPV18(OR = 0.12, 95%CI:0.01-1.16 were significantly reduced for vaccinated adolescents however, the risk for HPV16 was not significantly decreased (OR = 0.63, 95%CI:0.18-2.20.HPV Prevalence is extremely high in inner-city female adolescents. Administration of the HPV vaccine reduced the risk for cervical HPV; however continued follow-up is required to assess the protection for HPV at all sites

  7. Reparative Spheroids in HPV-Associated Chronic Cervicitis

    Directory of Open Access Journals (Sweden)

    Gennadiy T. Sukhikh

    2013-09-01

    Full Text Available Background: Spheroid cell structures (SCS described in cell culture are used to study cell-cell and cell-matrix interactions. However, the role of the SCS in the repair process in vivo remains unexplored. The aim of the study was to examine the cellular composition of the spherical structures and their functional significance in the repair of the squamous epithelium in human papilloma virus-associated chronic cervicitis (HPV-CC. Methods and Results: The cytology and biopsy materials from 223 patients with HPV-CC were subjected to molecular testing for HPV DNA by Real-Time Polymerase Chain Reaction (Real-Time PCR with genotyping and chromogenic in situ hybridization (CISH, as well as immunocytological and immunohistochemical analyses of p16INK4A, Ki67, SMA, Vimentin, CD34, E-cadherin, Oct4, CD44, CKW markers. In the stem cell niche zone, these spheroid structures were discovered having proliferative activity and showing signs of producing stem cells involved in the repair of the cervical mucosa in HPV-CC. Conclusion: The persistence of the HPV in the stem cell niche zone cells in the cervix determines the chronization of inflammation in this area, with the ability to perform pathological repair. The immunophenotype of the spheroid cell structures in the HPV-CC includes cells with signs of stem cells (‘stemness’ and the mesenchymal-epithelial transition.

  8. HPV vaccines: a controversial issue?

    Science.gov (United States)

    Nicol, A F; Andrade, C V; Russomano, F B; Rodrigues, L L S; Oliveira, N S; Provance, D W

    2016-01-01

    Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.

  9. HPV vaccines: a controversial issue?

    Directory of Open Access Journals (Sweden)

    A.F. Nicol

    2016-01-01

    Full Text Available Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.

  10. High-risk human papillomavirus (HPV screening and detection in healthy patient saliva samples: a pilot study

    Directory of Open Access Journals (Sweden)

    Wang Robert C

    2011-10-01

    Full Text Available Abstract Background The human papillomaviruses (HPV are a large family of non-enveloped DNA viruses, mainly associated with cervical cancers. Recent epidemiologic evidence has suggested that HPV may be an independent risk factor for oropharyngeal cancers. Evidence now suggests HPV may modulate the malignancy process in some tobacco- and alcohol-induced oropharynx tumors, but might also be the primary oncogenic factor for inducing carcinogenesis among some non-smokers. More evidence, however, is needed regarding oral HPV prevalence among healthy adults to estimate risk. The goal of this study was to perform an HPV screening of normal healthy adults to assess oral HPV prevalence. Methods Healthy adult patients at a US dental school were selected to participate in this pilot study. DNA was isolated from saliva samples and screened for high-risk HPV strains HPV16 and HPV18 and further processed using qPCR for quantification and to confirm analytical sensitivity and specificity. Results Chi-square analysis revealed the patient sample was representative of the general clinic population with respect to gender, race and age (p Conclusions The successful recruitment and screening of healthy adult patients revealed HPV16, but not HPV18, was present in a small subset. These results provide new information about oral HPV status, which may help to contextualize results from other studies that demonstrate oral cancer rates have risen in the US among both females and minorities and in some geographic areas that are not solely explained by rates of tobacco and alcohol use. The results of this study may be of significant value to further our understanding of oral health and disease risk, as well as to help design future studies exploring the role of other factors that influence oral HPV exposure, as well as the short- and long-term consequences of oral HPV infection.

  11. Concise Review: Heteroplasmic Mitochondrial DNA Mutations and Mitochondrial Diseases: Toward iPSC-Based Disease Modeling, Drug Discovery, and Regenerative Therapeutics.

    Science.gov (United States)

    Hatakeyama, Hideyuki; Goto, Yu-Ichi

    2016-04-01

    Mitochondria contain multiple copies of their own genome (mitochondrial DNA; mtDNA). Once mitochondria are damaged by mutant mtDNA, mitochondrial dysfunction is strongly induced, followed by symptomatic appearance of mitochondrial diseases. Major genetic causes of mitochondrial diseases are defects in mtDNA, and the others are defects of mitochondria-associating genes that are encoded in nuclear DNA (nDNA). Numerous pathogenic mutations responsible for various types of mitochondrial diseases have been identified in mtDNA; however, it remains uncertain why mitochondrial diseases present a wide variety of clinical spectrum even among patients carrying the same mtDNA mutations (e.g., variations in age of onset, in affected tissues and organs, or in disease progression and phenotypic severity). Disease-relevant induced pluripotent stem cells (iPSCs) derived from mitochondrial disease patients have therefore opened new avenues for understanding the definitive genotype-phenotype relationship of affected tissues and organs in various types of mitochondrial diseases triggered by mtDNA mutations. In this concise review, we briefly summarize several recent approaches using patient-derived iPSCs and their derivatives carrying various mtDNA mutations for applications in human mitochondrial disease modeling, drug discovery, and future regenerative therapeutics. © 2016 AlphaMed Press.

  12. Association of serum cytokines with oral HPV clearance.

    Science.gov (United States)

    Lam, Jennifer O; Bream, Jay H; Sugar, Elizabeth A; Coles, Christian L; Weber, Kathleen M; Burk, Robert D; Wiley, Dorothy J; Cranston, Ross D; Reddy, Susheel; Margolick, Joseph B; Strickler, Howard D; Wentz, Alicia; Jacobson, Lisa; Guo, Yingshi; Xiao, Weihong; Gillison, Maura L; D'Souza, Gypsyamber

    2016-07-01

    Initial studies suggest higher serum levels of some pro-inflammatory cytokines may be associated with decreased cervical human papillomavirus (HPV) clearance. However, the relationship of cytokines with oral HPV clearance has not been explored. From 2010 to 2014, oral rinse and serum samples were collected semi-annually from 1601 adults. Oral rinse samples were tested for HPV DNA using PCR. Based on oral HPV results, 931 serum samples were selected for cytokine evaluation to include a roughly equal number of prevalent (n=307), incident (n=313), and no oral HPV infections (n=311). Electrochemiluminescence multiplex assays were used to determine the concentrations of IL-6, IL-8, TNF-α, IFN-γ, IL-1β, IL-2, IL-4, IL-10, IL-12 and IL-13. The relationship between serum cytokine concentrations (categorized into quartiles) and oral HPV clearance was evaluated with Wei-Lin-Weissfeld regression models, adjusting for HPV infection type (prevalent vs. incident), age, HIV status, and CD4 T cell count. Higher TNF-α concentration was associated with decreased clearance in men (highest vs. lowest quartile, adjusted hazard ratio [aHR]=0.52, 95% CI=0.34-0.79) and women (aHR=0.76, 95% confidence interval [CI]=0.55-1.04), with stronger associations in men than women (p-interaction=0.049). Higher IL-2 concentration was associated with reduced clearance in men (aHR=0.69, 95% CI=0.50-0.95), but not women (p-interaction=0.058). Results were similar within CD4 T cell strata (CD4⩾500 or CD4HPV infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Human papillomavirus prevalence among indigenous and non-indigenous Australian women prior to a national HPV vaccination program

    Directory of Open Access Journals (Sweden)

    Condon John R

    2011-09-01

    Full Text Available Abstract Background Indigenous women in Australia have a disproportionate burden of cervical cancer despite a national cervical screening program. Prior to introduction of a national human papilloma virus (HPV vaccination program, we determined HPV genotype prevalence by Indigenous status and residence in remote areas. Methods We recruited women aged 17 to 40 years presenting to community-based primary health services for routine Pap screening across Australia. A liquid-based cytology (LBC cervical specimen was tested for HPV DNA using the AMPLICOR HPV-DNA test and a PGMY09/11-based HPV consensus PCR; positive specimens were typed by reverse hybridization. We calculated age-adjusted prevalence by weighting to relevant population data, and determined predictors of HPV-DNA positivity by age, Indigenous status and area of residence using logistic regression. Results Of 2152 women (655 Indigenous, prevalence of the high-risk HPV genotypes was similar for Indigenous and non-Indigenous women (HPV 16 was 9.4% and 10.5%, respectively; HPV 18 was 4.1% and 3.8%, respectively, and did not differ by age group. In younger age groups, the prevalence of other genotypes also did not differ, but in those aged 31 to 40 years, HPV prevalence was higher for Indigenous women (35% versus 22.5%; P Conclusion Although we found no difference in the prevalence of HPV16/18 among Australian women by Indigenous status or, for Indigenous women, residence in remote regions, differences were found in the prevalence of risk factors and some other HPV genotypes. This reinforces the importance of cervical screening as a complement to vaccination for all women, and the value of baseline data on HPV genotype prevalence by Indigenous status and residence for the monitoring of vaccine impact.

  14. HPV Vaccine Information for Young Women

    Science.gov (United States)

    ... STD on Facebook Sexually Transmitted Diseases (STDs) HPV Vaccine Information For Young Women Language: English Español (Spanish) ... media/releases/2016/p1020-hpv-shots.html A vaccines is available to prevent the human papillomavirus (HPV) ...

  15. Human papillomavirus type 29 (HPV-29), an HPV type cross-hybridizing with HPV-2 and with HPV-3-related types.

    OpenAIRE

    Favre, M; Croissant, O; Orth, G

    1989-01-01

    The cloning and partial characterization of human papillomavirus (HPV) type 29 is presented. By hybridization analyses, this virus appears to be related to HPV types associated with common warts and HPV types associated with flat warts.

  16. Gardasil 9 Protects against Additional HPV Types

    Science.gov (United States)

    A summary of results from a large randomized clinical trial that shows a new human papillomavirus (HPV) vaccine effectively prevented infection and disease caused by seven HPV types that cause cancer and two HPV types that cause genital warts.

  17. Preventing Cervical Cancer with HPV Vaccines

    Science.gov (United States)

    Cervical cancer can be prevented with HPV vaccines. NCI-supported researchers helped establish HPV as a cause of cervical cancer. They also helped create the first HPV vaccines, were involved in the vaccine trials, and contribute to ongoing studies.

  18. Human Papillomavirus (HPV) and Oropharyngeal Cancer

    Science.gov (United States)

    ... Español (Spanish) Recommend on Facebook Tweet Share Compartir Human papillomavirus (HPV) can cause serious health problems, including ... any health problems. What is genital HPV? Genital human papillomavirus (also called HPV) is the most common ...

  19. Specificity of the Linear Array HPV Genotyping Test for detecting human papillomavirus genotype 52 (HPV-52)

    OpenAIRE

    Kocjan, Boštjan; Poljak, Mario; Oštrbenk, Anja

    2015-01-01

    Introduction: HPV-52 is one of the most frequent human papillomavirus (HPV) genotypes causing significant cervical pathology. The most widely used HPV genotyping assay, the Roche Linear Array HPV Genotyping Test (Linear Array), is unable to identify HPV- 52 status in samples containing HPV-33, HPV-35, and/or HPV-58. Methods: Linear Array HPV-52 analytical specificity was established by testing 100 specimens reactive with the Linear Array HPV- 33/35/52/58 cross-reactive probe, but not with the...

  20. Spotlight on the 9-valent HPV vaccine

    Directory of Open Access Journals (Sweden)

    Lopalco PL

    2016-12-01

    Full Text Available Pier Luigi Lopalco Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy Abstract: Starting in 2006, vaccination against human papillomavirus (HPV has been progressively implemented in most developed countries. Two vaccines have been successfully used, a bivalent vaccine targeting HPV-related cancers (bHPV and a quadrivalent vaccine (qHPV targeting both HPV-related cancers and genital warts. Between December 2014 and June 2015, a new nonavalent HPV vaccine (9vHPV was granted marketing authorization in the USA and Europe. The 9vHPV was developed from the qHPV and includes five additional HPV types that should increase the level of protection toward HPV-related cancers. Efficacy and/or immunogenicity of 9vHPV has been assessed in eight clinical studies. The 9vHPV vaccine induced a very robust immune response against all vaccine types, with seroconversion rates close to 100%. The safety profile of 9vHPV is comparable to that of qHPV. Local reactions, especially swelling, have been more frequently reported after 9vHPV than qHPV, and this slightly increases when the 9vHPV is coadministered with other vaccines. The additional coverage offered by the 9vHPV may prevent a significant proportion of HPV-related cancers (variable between 8% and 18% depending on the local distribution of high-risk HPV types in the population. It is impossible, at present, to anticipate the actual impact of the wide use of the 9vHPV in comparison with the bHPV or the qHPV, since it depends on many variables including duration of protection, potential cross-protection toward nonvaccine types, and herd immunity effect. Keywords: human papillomavirus vaccine, immunogenicity, vaccine safety, cervical cancer, head and neck cancer, genital warts

  1. Spotlight on the 9-valent HPV vaccine.

    Science.gov (United States)

    Lopalco, Pier Luigi

    2017-01-01

    Starting in 2006, vaccination against human papillomavirus (HPV) has been progressively implemented in most developed countries. Two vaccines have been successfully used, a bivalent vaccine targeting HPV-related cancers (bHPV) and a quadrivalent vaccine (qHPV) targeting both HPV-related cancers and genital warts. Between December 2014 and June 2015, a new nonavalent HPV vaccine (9vHPV) was granted marketing authorization in the USA and Europe. The 9vHPV was developed from the qHPV and includes five additional HPV types that should increase the level of protection toward HPV-related cancers. Efficacy and/or immunogenicity of 9vHPV has been assessed in eight clinical studies. The 9vHPV vaccine induced a very robust immune response against all vaccine types, with seroconversion rates close to 100%. The safety profile of 9vHPV is comparable to that of qHPV. Local reactions, especially swelling, have been more frequently reported after 9vHPV than qHPV, and this slightly increases when the 9vHPV is coadministered with other vaccines. The additional coverage offered by the 9vHPV may prevent a significant proportion of HPV-related cancers (variable between 8% and 18%) depending on the local distribution of high-risk HPV types in the population. It is impossible, at present, to anticipate the actual impact of the wide use of the 9vHPV in comparison with the bHPV or the qHPV, since it depends on many variables including duration of protection, potential cross-protection toward nonvaccine types, and herd immunity effect.

  2. Immunogenicity of next-generation HPV vaccines in non-human primates: Measles-vectored HPV vaccine versus Pichia pastoris recombinant protein vaccine.

    Science.gov (United States)

    Gupta, Gaurav; Giannino, Viviana; Rishi, Narayan; Glueck, Reinhard

    2016-09-07

    Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide. HPVs are oncogenic small double-stranded DNA viruses that are the primary causal agent of cervical cancer and other types of cancers, including in the anus, oropharynx, vagina, vulva, and penis. Prophylactic vaccination against HPV is an attractive strategy for preventing cervical cancer and some other types of cancers. However, there are few safe and effective vaccines against HPV infections. Current first-generation commercial HPV vaccines are expensive to produce and deliver. The goal of this study was to develop an alternate potent HPV recombinant L1-based vaccines by producing HPV virus-like particles into a vaccine that is currently used worldwide. Live attenuated measles virus (MV) vaccines have a well-established safety and efficacy record, and recombinant MV (rMV) produced by reverse genetics may be useful for generating candidate HPV vaccines to meet the needs of the developing world. We studied in non-human primate rMV-vectored HPV vaccine in parallel with a classical alum adjuvant recombinant HPV16L1 and 18L1 protein vaccine produced in Pichia pastoris. A combined prime-boost approach using both vaccines was evaluated, as well as immune interference due to pre-existing immunity against the MV. The humoral immune response induced by the MV, Pichia-expressed vaccine, and their combination as priming and boosting approaches was found to elicit HPV16L1 and 18L1 specific total IgG and neutralizing antibody titres. Pre-existing antibodies against measles did not prevent the immune response against HPV16L1 and 18L1. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Ny generasjon HPV-tester på vent

    OpenAIRE

    Sørbye, Sveinung Wergeland; Gutteberg, Tore Jarl; Vintermyr, Olav Karsten

    2010-01-01

    Ny forskning viser at gentester for humant papillomvirus (HPV) siler ut de behandlingstrengende i langt større grad enn celleprøver. Samtidig er det grunn til å tro at mRNA-tester bør velges fremfor DNA-tester.

  4. Prediction of cervical intraepithelial neoplasia grade 2+ (CIN2+) using HPV DNA testing after a diagnosis of atypical squamous cell of undetermined significance (ASC-US) in Catalonia, Spain

    Science.gov (United States)

    2012-01-01

    Background A protocol for cervical cancer screening among sexually active women 25 to 65 years of age was introduced in 2006 in Catalonia, Spain to increase coverage and to recommend a 3-year-interval between screening cytology. In addition, Human Papillomavirus (HPV) was offered as a triage test for women with a diagnosis of atypical squamous cells of undetermined significance (ASC-US). HPV testing was recommended within 3 months of ASC-US diagnosis. According to protocol, HPV negative women were referred to regular screening including a cytological exam every 3 years while HPV positive women were referred to colposcopy and closer follow-up. We evaluated the implementation of the protocol and the prediction of HPV testing as a triage tool for cervical intraepithelial lesions grade two or worse (CIN2+) in women with a cytological diagnosis of ASC-US. Methods During 2007-08 a total of 611 women from five reference laboratories in Catalonia with a novel diagnosis of ASC-US were referred for high risk HPV (hrHPV) triage using high risk Hybrid Capture version 2. Using routine record linkage data, women were followed for 3 years to evaluate hrHPV testing efficacy for predicting CIN2+ cases. Logistic regression analysis was used to estimate the odds ratio for CIN2 +. Results Among the 611 women diagnosed with ASC-US, 493 (80.7%) had at least one follow-up visit during the study period. hrHPV was detected in 48.3% of the women at study entry (mean age 35.2 years). hrHPV positivity decreased with increasing age from 72.6% among women younger than 25 years to 31.6% in women older than 54 years (p < 0.01). At the end of the 3 years follow-up period, 37 women with a diagnosis of CIN2+ (18 CIN2, 16 CIN3, 2 cancers, and 1 with high squamous intraepithelial lesions -HSIL) were identified and all but one had a hrHPV positive test at study entry. Sensitivity to detect CIN2+ of hrHPV was 97.2% (95%confidence interval (CI) = 85.5-99.9) and specificity was 68.3% (95%CI = 63

  5. Human papillomavirus DNA detection in sperm using polymerase chain reaction.

    Science.gov (United States)

    Olatunbosun, O; Deneer, H; Pierson, R

    2001-03-01

    To detect human papillomavirus (HPV) in semen and find if sperm washing removes HPV DNA. Amplification by nested polymerase chain reaction (PCR) was used to detect viral DNA sequences in semen samples from 85 volunteers. Forty-five men had historical or clinical evidence of genital HPV infection (study group) and 40 were healthy, clinically HPV-negative semen donors. We detected HPV DNA in the sperm cells of 24 of 45 subjects (53%) with past or current HPV infections in contrast to three of 40 healthy subjects (8%) (P HPV in 21 of 32 subjects (66%) with identifiable lesions and six of 53 (11%) without them (P sperm cells with HPV reduced cellular HPV DNA below detectable levels in only two cases. HPV is present in sperm cells from infected and apparently healthy subjects, and sperm washing does not eliminate the risk of HPV transmission to recipients. We suggest that HPV DNA testing should be done on the semen of prospective donors, and those with positive tests should be excluded from donation.

  6. Evolution and taxonomic classification of alphapapillomavirus 7 complete genomes: HPV18, HPV39, HPV45, HPV59, HPV68 and HPV70.

    Directory of Open Access Journals (Sweden)

    Zigui Chen

    Full Text Available The species Alphapapillomavirus 7 (alpha-7 contains human papillomavirus genotypes that account for 15% of invasive cervical cancers and are disproportionately associated with adenocarcinoma of the cervix. Complete genome analyses enable identification and nomenclature of variant lineages and sublineages.The URR/E6 region was sequenced to screen for novel variants of HPV18, 39, 45, 59, 68, 70, 85 and 97 from 1147 cervical samples obtained from multiple geographic regions that had previously been shown to contain an alpha-7 HPV isolate. To study viral heterogeneity, the complete 8 kb genome of 128 isolates, including 109 sequenced for this analysis, were annotated and analyzed. Viral evolution was characterized by constructing phylogenic trees using maximum-likelihood and Bayesian algorithms. Global and pairwise alignments were used to calculate total and ORF/region nucleotide differences; lineages and sublineages were assigned using an alphanumeric system. The prototype genome was assigned to the A lineage or A1 sublineage.The genomic diversity of alpha-7 HPV types ranged from 1.1% to 6.7% nucleotide sequence differences; the extent of genome-genome pairwise intratype heterogeneity was 1.1% for HPV39, 1.3% for HPV59, 1.5% for HPV45, 1.6% for HPV70, 2.1% for HPV18, and 6.7% for HPV68. ME180 (previously a subtype of HPV68 was designated as the representative genome for HPV68 sublineage C1. Each ORF/region differed in sequence diversity, from most variable to least variable: noncoding region 1 (NCR1 / noncoding region 2 (NCR2 > upstream regulatory region (URR > E6 / E7 > E2 / L2 > E1 / L1.These data provide estimates of the maximum viral genomic heterogeneity of alpha-7 HPV type variants. The proposed taxonomic system facilitates the comparison of variants across epidemiological and molecular studies. Sequence diversity, geographic distribution and phylogenetic topology of this clinically important group of HPVs suggest an independent evolutionary

  7. HPV 16 Is Related to the Progression of Cervical Intraepithelial Neoplasia Grade 2: A Case Series

    Directory of Open Access Journals (Sweden)

    Maria Gabriela Loffredo D’Ottaviano

    2013-01-01

    Full Text Available Purpose. To describe the acquisition, persistence, and clearance of HPV infection in women with CIN 2 followed up for 12 months. Methods. Thirty-seven women with CIN 2 biopsy, who have proven referral to cervical smear showing low-grade squamous intraepithelial lesions or atypical squamous cells of undetermined significance and tested for HPV, were followed up for one year with cervical smear, colposcopy, and HPV test every three months. HPV DNA was detected by the polymerase chain reaction and genotyping by reverse line blot hybridization assay. Results. CIN 2 regression rate was 49% (18/37, persistence as CIN 1 or CIN 2 was 22% (8/37, and progression to CIN 3 was 29% (11/37. Multiple HPV types were observed at admission in 41% (15/37 of cases. HPV 16 was detected at admission in 58% (11/19 of the cases that persisted/progressed and in 39% (7/18 of the cases that regressed. HPV 16 was considered possibly causal in 67% (10/15 of the cases that persisted or progressed and in 10% (1/10 of the cases that regressed (P=0.01. Conclusion. Multiple HPV infections were frequently detected among women with CIN 2 at admission and during the followup. The CIN 2 associated with HPV 16 was more likely to persist or to progress to CIN 3.

  8. Current trends in the etiology and diagnosis of HPV-related head and neck cancers

    Science.gov (United States)

    Chai, Ryan C; Lambie, Duncan; Verma, Mukesh; Punyadeera, Chamindie

    2015-01-01

    Human papilloma virus (HPV) infection is a major risk factor for a distinct subset of head and neck squamous cell carcinoma (HNSCC). The current review summarizes the epidemiology of HNSCC and the disease burden, the infectious cycle of HPV, the roles of viral oncoproteins, E6 and E7, and the downstream cellular events that lead to malignant transformation. Current techniques for the clinical diagnosis of HPV-associated HNSCC will also be discussed, that is, the detection of HPV DNA, RNA, and the HPV surrogate marker, p16 in tumor tissues, as well as HPV-specific antibodies in serum. Such methods do not allow for the early detection of HPV-associated HNSCC and most cases are at an advanced stage upon diagnosis. Novel noninvasive approaches using oral fluid, a clinically relevant biological fluid, allow for the detection of HPV and cellular alterations in infected cells, which may aid in the early detection and HPV-typing of HNSCC tumors. Noninvasive diagnostic methods will enable early detection and intervention, leading to a significant reduction in mortality and morbidity associated with HNSCC. PMID:25644715

  9. From Human Papillomavirus (HPV) Detection to Cervical Cancer Prevention in Clinical Practice

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sin Hang, E-mail: shlee01@snet.net; Vigliotti, Jessica S.; Vigliotti, Veronica S.; Jones, William [Department of Pathology, Milford Hospital, 300 Seaside Ave., Milford, CT 06460 (United States)

    2014-10-02

    The newly gained knowledge of the viral etiology in cervical carcinogenesis has prompted industrial interests in developing virology-based tools for cervical cancer prevention. Due to the long incubation period from viral infection to developing an invasive cancer, a process whose outcome is influenced by numerous life-style and genetic factors, the true efficacy of the genotype-specific human papillomavirus (HPV) vaccines in cervical cancer prevention cannot be determined for another 30 years. Most HPV DNA test kits designed to replace the traditional Papanicolaou (Pap) smears for precancer detection lack the analytical sensitivity and specificity to comprehensively detect all potentially carcinogenic HPVs and to perform reliable genotyping. The authors implemented the classic nested PCR and Sanger DNA-sequencing technology for routine HPV testing. The results showed a true negative HPV PCR invariably indicates the absence of precancerous cells in the cytology samples. However, 80.5% of single positive HPV-16 tests and 97.3% of single positive HPV-18 tests were associated with a negative or a largely self-reversible Pap cytology. Routine sensitive and reliable HPV type-specific or perhaps even variant-specific methods are needed to address the issues of persistence of HPV infection if a virology-based primary cervical screen is used to replace the Pap cytology screening paradigm.

  10. Principles and analytical performance of Abbott RealTime High Risk HPV test.

    Science.gov (United States)

    Huang, Shihai; Tang, Ning; Mak, Wai-Bing; Erickson, Brian; Salituro, John; Li, Yuhong; Krumpe, Evelyn; Schneider, George; Yu, Hong; Robinson, John; Abravaya, Klara

    2009-07-01

    Abbott RealTime High Risk (HR) HPV is a new automated, qualitative real-time PCR test for detection of DNA from 14 high-risk human papillomavirus (HPV) types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) in cervical specimens. The test can also differentiate between HPV 16, HPV 18 and non-HPV 16/18 types in a single reaction. This article describes the principles of assay design and the analytical performance of Abbott RealTime HR HPV. The analytical performance characteristics of Abbott RealTime HR HPV were evaluated in terms of its sensitivity for each of the 14 high-risk types included in the test, specificity (cross-reactivity), potential for interference by substances that may be present in cervical specimens, and reproducibility. Abbott RealTime HR HPV provided sensitive detection of the 14 high-risk HPV types included in the test. It was also highly specific to the HPV types targeted by the test and did not show cross-reactivity with 15 low-risk HPV types tested, or non-specific reactivity with other common microorganisms that may be present in the female anogenital tract. Test results were not impacted by potential interfering substances evaluated in the study. The test generated highly reproducible results in an in-house study and in studies carried out at 13 external evaluation sites. Abbott RealTime HR HPV demonstrated a robust analytical performance with reproducible and reliable results.

  11. Evaluation of the Clinical Performance of the HPV-Risk Assay Using the VALGENT-3 Panel.

    Science.gov (United States)

    Polman, N J; Oštrbenk, A; Xu, L; Snijders, P J F; Meijer, C J L M; Poljak, M; Heideman, D A M; Arbyn, M

    2017-12-01

    Human papillomavirus (HPV) testing is increasingly being incorporated into cervical cancer screening. The Validation of HPV Genotyping Tests (VALGENT) is a framework designed to evaluate the clinical performance of various HPV tests relative to that of the validated and accepted comparator test in a formalized and uniform manner. The aim of this study was to evaluate the clinical performance of the HPV-Risk assay with samples from the VALGENT-3 panel and to compare its performance to that of the clinically validated Hybrid Capture 2 assay (HC2). The VALGENT-3 panel comprises 1,300 consecutive samples from women participating in routine cervical cancer screening and is enriched with 300 samples from women with abnormal cytology. DNA was extracted from original ThinPrep PreservCyt medium aliquots, and HPV testing was performed using the HPV-Risk assay by investigators blind to the clinical data. HPV prevalence was analyzed, and the clinical performance of the HPV-Risk assay for the detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) and CIN2 or worse (CIN2+) relative to the performance of HC2 was assessed. The sensitivity of the HPV-Risk assay for the detection of CIN3+ was similar to that of HC2 (relative sensitivity, 1.00; 95% confidence interval [CI], 0.95 to 1.05; P = 1.000), but the specificity of the HPV-Risk assay was significantly higher than that of HC2 (relative specificity, 1.02; 95% CI, 1.01 to 1.04; P performance of the HPV-Risk assay for the detection of CIN3+ and CIN2+ was noninferior to that of HC2, with all P values being ≤0.006. In conclusion, the HPV-Risk assay demonstrated noninferiority to the clinically validated HC2 by the use of samples from the VALGENT-3 panel for test validation and comparison. Copyright © 2017 Polman et al.

  12. Elimination of high-risk human papillomavirus type HPV16 infection by 'Praneem' polyherbal tablet in women with early cervical intraepithelial lesions.

    Science.gov (United States)

    Shukla, Shirish; Bharti, Alok C; Hussain, Showket; Mahata, Sutapa; Hedau, Suresh; Kailash, Uma; Kashyap, Veena; Bhambhani, Suresh; Roy, Meera; Batra, Swaraj; Talwar, G P; Das, Bhudev C

    2009-12-01

    'Praneem', a polyherbal formulation developed by us, has successfully completed Phase II efficacy study for treatment of abnormal vaginal discharge due to reproductive tract infections that act as co-factors for HPV persistence. In the present study we evaluated potential anti-HPV activity of Praneem in women infected with high risk HPV type 16. Twenty women molecularly diagnosed positive for HPV16 infection without or with low grade squamous intraepithelial lesion (LSIL) or inflammation were assigned to receive intra-vaginal, topical application of either Praneem tablet or placebo for 30 days excluding the days of menstrual period and were evaluated for persistence of HPV infection using HPV L1 consensus and HPV type 16-specific PCR as primary outcome. One course of Praneem treatment resulted in elimination of HPV in 6 out of 10 (60%) cases. A repeat treatment of four patients with persisting HPV infection resulted in clearance of HPV in two additional cases resulting in an overall 80% clearance of HPV 16 as against a spontaneous clearance of 10% (1/10) seen in the placebo arm. The elimination of HPV DNA was found to be accompanied by marked improvement in clinical symptoms and cytological abnormalities of Praneem-treated patients. Our results showed for the first time that a 30-day intra-vaginal application of the Praneem can result in elimination of HPV infection from the uterine cervix.

  13. The Curcumin Analogue 1,5-Bis(2-hydroxyphenyl)-1,4-pentadiene-3-one Induces Apoptosis and Downregulates E6 and E7 Oncogene Expression in HPV16 and HPV18-Infected Cervical Cancer Cells.

    Science.gov (United States)

    Paulraj, Felicia; Abas, Faridah; Lajis, Nordin H; Othman, Iekhsan; Hassan, Sharifah Syed; Naidu, Rakesh

    2015-06-29

    In an effort to study curcumin analogues as an alternative to improve the therapeutic efficacy of curcumin, we screened the cytotoxic potential of four diarylpentanoids using the HeLa and CaSki cervical cancer cell lines. Determination of their EC50 values indicated relatively higher potency of 1,5-bis(2-hydroxyphenyl)-1,4-pentadiene-3-one (MS17, 1.03 ± 0.5 μM; 2.6 ± 0.9 μM) and 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (MS13, 2.8 ± 0.4; 6.7 ± 2.4 μM) in CaSki and HeLa, respectively, with significantly greater growth inhibition at 48 and 72 h of treatment compared to the other analogues or curcumin. Based on cytotoxic and anti-proliferative activity, MS17 was selected for comprehensive apoptotic studies. At 24 h of treatment, fluorescence microscopy detected that MS17-exposed cells exhibited significant morphological changes consistent with apoptosis, corroborated by an increase in nucleosomal enrichment due to DNA fragmentation in HeLa and CaSki cells and activation of caspase-3 activity in CaSki cells. Quantitative real-time PCR also detected significant down-regulation of HPV18- and HPV16-associated E6 and E7 oncogene expression following treatment. The overall data suggests that MS17 treatment has cytotoxic, anti-proliferative and apoptosis-inducing potential in HPV-positive cervical cancer cells. Furthermore, its role in down-regulation of HPV-associated oncogenes responsible for cancer progression merits further investigation into its chemotherapeutic role for cervical cancer.

  14. Human papillomavirus (HPV) is not the main cause of preinvasive and invasive cervical cancer among patients in Delta Region, Egypt.

    Science.gov (United States)

    Thabet, Mahmoud; Hemida, Reda; Hasan, Mohammad; Elshamy, Maged; Elfaraash, Mohammad; Emam, Mohammad

    2014-01-01

    Cervical cancer remains a significant problem worldwide particularly in underdeveloped countries. It is necessary to have a persistent infection of the cervix with a high-risk or oncogenic human Papillomavirus (HPV) virus to develop cervical cancer. To study the association between HPV and pre-invasive and invasive cancer cervix among patients referred to Early Cancer Detection Clinic of Obstetrics and Gynecology Department, Mansoura University Hospital, Delta region, Egypt. Cervical specimens of 100 histologically confirmed premalignant and malignant cervical lesions were subjected to HPV detection and genotyping by extraction of DNA from cervical biopsy using a commercial PCR kit. HPV DNA testing was done, 36 cases were positive (36%). Correlations of age, duration of marriage, and parity were non significant (P = 0.56, 0.72, and 0.35 respectively) while correlations of residence, oral contraceptive use, smoking, and immunosuppresion were sig- nificant (P = 0.006, 0.001, 0.001, and 0.01 respectively). The prevalence of HPV in premalignant and malignant cervical lesions in our study was 39.5% & 33.3% respec tively. The commonest HPV genotypes associated with premalignant cervical lesions were HPV16; 11/17(64.7%) and HPV18; 11/17 (64.7%) mostly in the form of mul- tiple infections with HPV16+18; 7/17 (41.17%). The commonest HPV genotypes associated with malignant cervical lesions in our cases were HPV16; 15/19 (78.9%) and HPV18; 13/19 (68.42%) also in the form of multiple infections with HPV16+18; 10/19 (52.63%). The prevalence of HPV in premalignant and malignant cervical lesions was 39.5% & 33.3% respectively, this means that HPV is not the main cause of premalignant and malignant cervical lesions in Delta region in Egypt. HPV infection mostly in the form of multiple infections with HPV16+18 genotypes. Further studies are needed to clarify actual association of HPV and premalignant and malignant cervical lesions to determine the usefulness of HPV vaccination in

  15. Prevalence and risk factors for oral human papillomavirus infection in 129 women screened for cervical HPV infection.

    Science.gov (United States)

    Meyer, Moritz F; Huebbers, Christian U; Siefer, Oliver G; Vent, Julia; Engbert, Iris; Eslick, Guy D; Valter, Markus; Klussmann, Jens Peter; Preuss, Simon F

    2014-01-01

    Oncogenic human papillomaviruses (HPV) are known to be associated with carcinomas of the uterine cervix. Furthermore, current studies have shown that HPV-infection is also associated with a subtype of oropharyngeal cancers. In general, a sexual transmission of the viruses has been shown by numerous studies in the genital lesions. However, there are unknown factors regarding the prevalence and transmission of HPV in the oropharynx. The aim of this study was to evaluate HPV prevalence in the oropharynx in female participants with and without genital HPV infection. In addition, we analyzed risk factors for an oropharyngeal colonization with HPV in their sexual partners, too. 129 Female participants were tested for presence of HPV-DNA by oral lavage, brush cytology of the tonsils and of the cervix. In addition, 15 male partners of these patients were included in the study. HPV-DNA was detected by PCR (polymerase chain reaction) amplification. For HPV-genotyping, PCR products were hybridized with type-specific digoxigenin-labeled oligonucleotide probes and discriminated into 14 high risk (HR) and 6 low risk (LR)-HPV types. The 129 female and 15 male participants were interviewed by a standardized questionnaire for socioeconomic details, drinking, smoking and sexual behaviours. 59 (45.7%) Female participants were negative for a genital HPV-infection. Of these women, 3 (5.1%) showed a positive HPV-PCR result (HR and LR) in the oropharynx. 70 (54.3%) Female participants were positive for a genital HPV infection. In this group, 4 (5.7%) had a positive HPV-detection (HR and LR) in the oral cavity and oropharynx. Female participants with cervical HPV-infection had no higher risk for HPV-detection in the oropharynx (not significant). The analysis of sexual risk factors revealed no specific risk factor for an oral HPV-infection. A correlation between cervical and oral colonization by HPV could not be demonstrated in our small cohort. Our limited data suggest that sexual

  16. Detecção de HPV na mucosa oral e genital pela técnica PCR em mulheres com diagnóstico histopatológico positivo para HPV genital HPV detection in the oral and genital mucosa of women with positive histopathological exam for genital HPV, by means of the PCR

    Directory of Open Access Journals (Sweden)

    Therezita M. Peixoto Patury Galvão Castro

    2009-04-01

    Full Text Available A infecção do papilomavírus humano (HPV é uma das mais freqüentes doenças sexualmente transmissíveis em todo o mundo. A relação entre o HPV genital e oral permanece incerta, assim como o seu papel na carcinogênese oral. O objetivo deste estudo foi verificar a presença do DNA do HPV na mucosa oral e genital de mulheres com infecção genital por HPV, pela técnica de reação em cadeia de polimerase (PCR. FORMA DE ESTUDO: Coorte transversal. MATERIAL E MÉTODO: Trata-se de um estudo piloto, prospectivo, com 30 mulheres, idade de 14 a 51 anos, portadoras de infecção genital por HPV confirmada pelo exame de histopatológico. Todas as pacientes foram submetidas a exame e coleta por raspagem da cavidade oral e genital para pesquisa do DNA do HPV pela técnica PCR. RESULTADOS: Nenhuma das amostras da cavidade oral foi positiva para HPV, enquanto no genital, o HPV foi detectado em 17 (57% das 30 pacientes, principalmente o HPV 6b e 16. CONCLUSÃO: Os resultados mostraram maior porcentagem do HPV genital em relação à cavidade oral, e sugerem que o HPV genital não parece ser fator predisponente para a infecção oral no mesmo paciente.Infection by the Human Papilloma Virus (HPV is one of the most frequent sexually transmitted diseases all over the world. The relationship between oral and genital HPV remains uncertain, as it is with its role on oral carcinogenesis. The goal of the present investigation was to check for the presence of HPV DNA in the oral and genital mucosas of women with HPV genital infection, using the polymerase chain reaction (PCR. STUDY METHOD: Cross-sectional cohort. MATERIALS AND METHODS: this is a pilot and prospective study involving 30 women, aged between 14 and 51 years, with HPV genital infection, confirmed by histopathology. All the patients were submitted to the exam and sample collection by swabbing the oral and genital mucosas in order to test for HPV DNA through the PCR technique. RESULTS: none of the oral

  17. Product news Efficacy of Quadrivalent HPV Vaccine against HPV ...

    African Journals Online (AJOL)

    Product news. Efficacy of Quadrivalent HPV Vaccine against HPV Infection and Disease in Males. Anna R Giuliano, Joel M Palefsky, Stephen Goldstone, Edson D Moreira, Mary E Penny, Carlos Aranda, Eftyhia Vardas, Harald Moi, Heiko Jessen, Richard Hillman, Yen-Hwa Chang, Daron Ferris, Danielle Rouleau, Janine ...

  18. The presence of high-risk human papillomavirus (HPV) E6/E7 mRNA transcripts in a subset of sinonasal carcinomas is evidence of involvement of HPV in its etiopathogenesis.

    Science.gov (United States)

    Laco, Jan; Sieglová, Kateřina; Vošmiková, Hana; Dundr, Pavel; Němejcová, Kristýna; Michálek, Jaroslav; Čelakovský, Petr; Chrobok, Viktor; Mottl, Radovan; Mottlová, Alena; Tuček, Luboš; Slezák, Radovan; Chmelařová, Marcela; Sirák, Igor; Vošmik, Milan; Ryška, Aleš

    2015-10-01

    The aim of the study was to investigate prevalence of high-risk human papillomavirus (HR-HPV) infection in sinonasal carcinomas by immunohistochemistry, in situ hybridization, and polymerase chain reaction, detecting p16(INK4a) protein (p16) expression and presence of both HPV DNA and HPV E6/E7 messenger RNA (mRNA). The study comprised 47 males and 26 females, aged 23-83 years (median 62 years), mostly (67 %) with a squamous cell carcinoma (SCC). Of the tumors, 53 % arose in the nasal cavity, 42 % in the maxillary sinus, and 5 % in the ethmoid complex. The follow-up period ranged 1-241 months (median 19 months). HPV16, HPV18, or HPV35 were detected in 18/73 (25 %) tumors, 17 SCCs, and 1 small cell neuroendocrine carcinoma. There was a strong correlation between results of HPV detection methods and p16 expression (p < 0.005). HPV-positive SCCs occurred more frequently in smokers (p = 0.04) and were more frequently p16-positive (p < 0.0001) and nonkeratinizing (p = 0.02), the latter occurring more commonly in nasal cavity (p = 0.025). Median survival for HPV-positive SCC patients was 30 months, while for HPV-negative SCC patients was 14 months (p = 0.23). In summary, we confirm that HR-HPV is actively involved in the etiopathogenesis of a significant subset of sinonasal SCCs. p16 may be used as a reliable surrogate marker for determination of HPV status also in sinonasal SCCs. Although we observed a trend toward better overall survival in HPV-positive SCCs, the prognostic impact of HPV status in sinonasal carcinomas needs to be elucidated by further studies.

  19. Oral inverted ductal papilloma: not related to HPV.

    Science.gov (United States)

    Do Canto, Alan Motta; Mistro, Florence Zumbaio; Kignel, Sergio; Martins, Fabiana; Palmieri, Michelle; Braz-Silva, Paulo Henrique

    2017-03-15

    Oral inverted ductal papilloma (OIDP) is a rare, nonrecurrent,benign lesion of salivary glands. The etiologyis still poorly understood; the correlation with humanpapilloma virus (HPV) is controversial. Herein wepresent a 74-year-old man with a tumor in lower lip.Incisional biopsy was performed and the histologicaldiagnosis was OIDP. Inno-LiPA assay, based onpolymerase chain reaction and in situ hybridizationwas used to assess for HPV with no detection of viralDNA. Surgical excision was performed without anyrecurrences after two years of follow-up.

  20. Cost-effectiveness of conventional cytology and HPV DNA testing for cervical cancer screening in Colombia Costo-efectividad de la citología y la tamización con pruebas de ADN-VPH para cáncer de cuello uterino en Colombia

    Directory of Open Access Journals (Sweden)

    Oscar Andrés-Gamboa

    2008-08-01

    Full Text Available OBJECTIVE: To assess cost-effectiveness of conventional cytology and HPV DNA testing for cervical-cancer screening in Colombia. MATERIAL AND METHODS: The National Cancer Institute of Colombia (NCIC in 2007 developed a Markov model on the natural history of cervical cancer; no screening, conventional cytology, and HPV DNA testing were compared. Only direct costs were used. Outcomes comprise cervical cancer mortality, years of life saved, and lifetime costs. Discounted incremental cost-effectiveness ratios were estimated and sensitivity analyses were conducted for key parameters. RESULTS: Depending on the screening strategy a 69-81% mortality reduction might be expected. The HPV DNA testing every five years is a cost-effective strategy (Incremental Cost-Effectiveness Ratio (ICER: USD$44/YLS if the cost per test is under USD$31. The effectiveness was sensitive to coverage and primarily to follow-up. CONCLUSIONS: HPV DNA testing is a cost-effective alternative for screening in Colombia. Not only high coverage but high follow-up rates are critical for successful screening programs.OBJETIVO: evaluar el costo-efectividad de la citología convencional y la prueba de ADN-VPH para tamización de cáncer cervical en Colombia. MATERIAL Y MÉTODOS: el Instituto Nacional de Cancerología de Colombia construyó en 2007 un modelo de Markov de historia natural del cáncer cervical. Se comparó "no tamización", citología convencional y prueba de ADN-VPH. Se utilizaron costos directos. Los desenlaces fueron mortalidad, años de vida ganados y costos. Se calcularon razones de costo-efectividad incremental. Se realizaron análisis de sensibilidad para parámetros clave. RESULTADOS: la mortalidad se redujo 69-81% según la estrategia. La tamización con ADN-VPH cada cinco años es costo-efectiva (ICER (Razón de Costo-Efectividad incremental por sus siglas en inglés: 44 dólares por año de vida saludable si los costos por prueba son menores a 31 dólares. La

  1. Improving cervical cancer screening in Mexico: results from the Morelos HPV Study Mejorando la detección oportuna del cáncer cervical en México: resultados del Estudio de VPH en Morelos

    OpenAIRE

    Yvonne Flores; David Bishai; Eduardo Lazcano; Keerti Shah; Attila Lörincz; Mauricio Hernández; Jorge Salmerón; Daron Ferris; Pilar Hernández; Mark E Sherman; Brigitte M Ronnett; Enrique Carmona; Alfredo Antúnez; Horacio Manzanares; Mario Uribe

    2003-01-01

    OBJECTIVE: The purpose of this paper is to describe some of the results of the Morelos HPV Study. The main objective of the Morelos HPV Study is to evaluate the use of human papillomavirus (HPV) DNA testing, as compared to the Papanicolaou (Pap) test, for cervical cancer (CC) screening. MATERIAL AND METHODS: The Morelos HPV Study is currently being conducted in Mexico, to examine the possibility of using HPV testing for CC screening. The HPV testing of self-collected vaginal and clinician-col...

  2. [Risk of cervical cancer and precancerous diseases in the oral HPV carriers].

    Science.gov (United States)

    He, Yi-feng; Zhang, Mei-ying; Feng, Ling-da; Yin, Yi-hua; Zhang, Rong; Di, Wen

    2013-08-01

    To evaluate the risk of the occurrence of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer in the oral HPV carriers through a population-based investigation in Shanghai. A total of 1200 cases of outpatients who attended the annual cervical examination and 50 preoperational cases of inpatients with CINIII or invasive cervical cancer were enrolled from three clinical centers in Shanghai. The oral HPV infection was determined by real-time PCR. In 1200-case cross-sectional study, the incidence rate of CIN was compared between the oral HPV positive and negative cohort. In 1250-case case-control study, the positive rate of oral HPV DNA test was compared among normal control group, CINI-III, and invasive cancer case groups, and all odds ratio (OR) values were calculated, respectively. The HPV transmission-related demographic and behavioral characters of the oral HPV carriers were also analyzed. The oral HPV carriers accounted for 5.9% (71/1200) of the investigated outpatients. The oral HPV DNA positive rates were gradually increased with the cervical disease grades, which were 5.8% (68/1182, normal), 2/13 (CIN I), 1/5 (CINII), 31.4% (11/35, CINIII) and 5/15 (invasive cancer). In cross-sectional cohort studies, the relative risks (RR) of CINI,II were 2.9 and 4.0 for oral HPV carriers, respectively. In case-control study, the OR values for CINI-III and invasive cervical cancer were 3.1(95%CI: 1.6-10.1), 4.2(95%CI: 1.7-28.4), 7.1(95%CI: 4.8-19.8) and 10.1(95%CI: 3.2-32.1), respectively. The oral sex and multi-sexual partner were two major risk factors for the oral and cervical HPV co-infection, HPV-related cervical cancer and precancerous diseases according to behavioral analysis. There are complicated transmission pathways between oral and cervical HPV. Oral HPV carriers should be intensively followed up and their oral HPV infection and HPV-related cervical diseases should be treated together.

  3. Characterization of HPV and host genome interactions in primary head and neck cancers

    Science.gov (United States)

    Parfenov, Michael; Pedamallu, Chandra Sekhar; Gehlenborg, Nils; Freeman, Samuel S.; Danilova, Ludmila; Bristow, Christopher A.; Lee, Semin; Hadjipanayis, Angela G.; Ivanova, Elena V.; Wilkerson, Matthew D.; Protopopov, Alexei; Yang, Lixing; Seth, Sahil; Song, Xingzhi; Tang, Jiabin; Ren, Xiaojia; Zhang, Jianhua; Pantazi, Angeliki; Santoso, Netty; Xu, Andrew W.; Mahadeshwar, Harshad; Wheeler, David A.; Haddad, Robert I.; Jung, Joonil; Ojesina, Akinyemi I.; Issaeva, Natalia; Yarbrough, Wendell G.; Hayes, D. Neil; Grandis, Jennifer R.; El-Naggar, Adel K.; Meyerson, Matthew; Park, Peter J.; Chin, Lynda; Seidman, J. G.; Hammerman, Peter S.; Kucherlapati, Raju; Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Bowlby, Reanne; Butterfield, Yaron S.N.; Carlsen, Rebecca; Cheng, Dean; Chu, Andy; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J.M.; Lee, Darlene; Li, Haiyan I.; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Robertson, A. Gordon; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Wong, Tina; Protopopov, Alexei; Santoso, Netty; Lee, Semin; Parfenov, Michael; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Ren, Xiaojia; Seth, Sahil; Haseley, Psalm; Zeng, Dong; Yang, Lixing; Xu, Andrew W.; Song, Xingzhi; Pantazi, Angeliki; Bristow, Christopher; Hadjipanayis, Angela; Seidman, Jonathan; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Akbani, Rehan; Casasent, Tod; Liu, Wenbin; Lu, Yiling; Mills, Gordon; Motter, Thomas; Weinstein, John; Diao, Lixia; Wang, Jing; Fan, You Hong; Liu, Jinze; Wang, Kai; Auman, J. Todd; Balu, Saianand; Bodenheimer, Tom; Buda, Elizabeth; Hayes, D. Neil; Hoadley, Katherine A.; Hoyle, Alan P.; Jefferys, Stuart R.; Jones, Corbin D.; Kimes, Patrick K.; Marron, J.S.; Meng, Shaowu; Mieczkowski, Piotr A.; Mose, Lisle E.; Parker, Joel S.; Perou, Charles M.; Prins, Jan F.; Roach, Jeffrey; Shi, Yan; Simons, Janae V.; Singh, Darshan; Soloway, Mathew G.; Tan, Donghui; Veluvolu, Umadevi; Walter, Vonn; Waring, Scot; Wilkerson, Matthew D.; Wu, Junyuan; Zhao, Ni; Cherniack, Andrew D.; Hammerman, Peter S.; Tward, Aaron D.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Jung, Joonil; Ojesina, Akinyemi I.; Carter, Scott L.; Zack, Travis I.; Schumacher, Steven E.; Beroukhim, Rameen; Freeman, Samuel S.; Meyerson, Matthew; Cho, Juok; Chin, Lynda; Getz, Gad; Noble, Michael S.; DiCara, Daniel; Zhang, Hailei; Heiman, David I.; Gehlenborg, Nils; Voet, Doug; Lin, Pei; Frazer, Scott; Stojanov, Petar; Liu, Yingchun; Zou, Lihua; Kim, Jaegil; Lawrence, Michael S.; Sougnez, Carrie; Lichtenstein, Lee; Cibulskis, Kristian; Lander, Eric; Gabriel, Stacey B.; Muzny, Donna; Doddapaneni, HarshaVardhan; Kovar, Christie; Reid, Jeff; Morton, Donna; Han, Yi; Hale, Walker; Chao, Hsu; Chang, Kyle; Drummond, Jennifer A.; Gibbs, Richard A.; Kakkar, Nipun; Wheeler, David; Xi, Liu; Ciriello, Giovanni; Ladanyi, Marc; Lee, William; Ramirez, Ricardo; Sander, Chris; Shen, Ronglai; Sinha, Rileen; Weinhold, Nils; Taylor, Barry S.; Aksoy, B. Arman; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Reva, Boris; Schultz, Nikolaus; Sumer, S. Onur; Sun, Yichao; Chan, Timo