Shanmugasundaram, Srinidhi; You, Jianxin
While the majority of Human papillomavirus (HPV) infections are transient and cleared within a couple of years following exposure, 10-20% of infections persist latently, leading to disease progression and, ultimately, various forms of invasive cancer. Despite the clinical efficiency of recently developed multivalent prophylactic HPV vaccines, these preventive measures are not effective against pre-existing infection. Additionally, considering that the burden associated with HPV is greatest in regions with limited access to preventative vaccination, the development of effective therapies targeting persistent infection remains imperative. This review discusses not only the mechanisms underlying persistent HPV infection, but also the promise of immunomodulatory therapeutic vaccines and small-molecular inhibitors, which aim to augment the host immune response against the viral infection as well as obstruct critical viral-host interactions.
Morfin-Maciel, Blanca María; Sotelo-Ortiz, Julieta Margarita
Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Most HPV infections are cleared within two years by the immune system. Only in 5% to 10% of infected women the infection persists determining a high risk of developing cervical intraepithelial neoplasia. The transfer factor (TF) or dialyzable leukocyte extract is an immunomodulator that has been successfully used as an adjuvant in the treatment of intracelular infections such as recurrent herpes virus diseases. One daily dose of transfer factor was given for five days and subsequently each week for five weeks to a group of women with persistent genital papillomavirus infection. We included 13 patients, aged 19 to 45 years, with first intercourse between the ages of 14 to 23, and a mean of three sexual partners in their lifetime. All of them had persistent HPV that had been treated before with local and ablative therapeutic options, including cervical freezing, cervical conization, cauterizing loop, imiquimod and podophyllin. Transfer factor was administered daily for 5 days, and subsequently at 7-day intervals for 5 weeks. We found a clinical significant improvement in the gynaecological evaluation of cervical, vaginal, vulvar and perineal lesions. No recurrences have developed for at least 1 year of follow-up. The use of transfer factor in women with HPV showed resolution of genital lesions, without recurrences for at least one year after the treatment was ended.
Giuliano, A R; Papenfuss, M; Nour, M; Canfield, L M; Schneider, A; Hatch, K
Research from the past several years has definitively shown intermediate and high risk-type human papillomavirus (HPV) infection to play a significant role in cervical carcinogenesis. Persistent compared with intermittent infection appears to confer an elevated risk, and cofactors may be necessary to allow the virus to progress to cervical cancer. We explored the association between circulating concentrations of the antioxidant nutrients (alpha- and beta-carotene, lutein, lycopene, beta-cryptoxanthin, alpha-tocopherol, gamma-tocopherol, and ascorbate) and persistent HPV infection among 123 low-income Hispanic women who were all nonsmokers and were not currently using vitamin and mineral supplements. In addition, the association between these nutrients and grade of cervical pathology, independent of HPV status, was assessed. Intermediate and high risk-type HPV infection was assessed by the Digene Hybrid Capture System at two time points, 3 months apart. At the second interview, cytology, colposcopy, and a fasting blood draw were conducted. Mean concentrations of serum and plasma antioxidant nutrients were calculated within categories of HPV status (two times HPV negative, one time HPV positive, and two times HPV positive) and colposcopy. Adjusted mean concentrations of serum beta-carotene, beta-cryptoxanthin, lutein, and alpha- and gamma-tocopherol were on average 24% (P < 0.05) lower among women two times HPV positive compared with either two times HPV negative or one time HPV positive. Independent of HPV status, alpha-tocopherol was significantly inversely associated with grade of cervical dysplasia (normal, 21.57 microM; cervical intraepithelial neoplasia III, 17.27 microM). The results obtained in this study need to be confirmed in larger cohort studies with a longer follow-up period.
Stensen, Signe; Kjær, Susanne K; Jensen, Signe Marie
Persistent genital infection with high-risk (HR) human papillomavirus (HPV) is a prerequisite for cervical cancer development. The aim of this study was to identify factors associated with type-specific persistence of HR HPV infections. From a population-based cohort of 40,399 women participating...
Ho, G Y; Burk, R D; Klein, S; Kadish, A S; Chang, C J; Palan, P; Basu, J; Tachezy, R; Lewis, R; Romney, S
Cervical dysplasia, also referred to as squamous intraepithelial lesion (SIL) in cytology or cervical intraepithelial neoplasia in histopathology, is thought to have the potential to advance in progressive stages to cervical cancer. However, not all cases of SIL progress, and most of the mild lesions spontaneously regress. Factors that govern regression, persistence, and progression of SIL are poorly understood. Our analysis sought to identify factors that determined persistence or regression of SIL. Seventy subjects with histopathologically confirmed cervical dysplasia were followed at 3-month intervals for 15 months. At each visit, the cervix was evaluated by Pap smear and colposcopy, and exfoliated cervicovaginal cells were analyzed for human papillomavirus (HPV) DNA. For each subject, data from every two consecutive visits were grouped as a pair. Persistent SIL was considered present if a lesion was detected at a visit (t) as well as at the next visit (t + 1) and absent if a lesion was detected at visit t but not at visit t + 1. A statistical model for time-dependent data correlated persistent SIL with various risk factors. Age, ethnicity, education, sexual behavior, smoking, and the use of oral contraceptives did not correlate with persistent SIL. The risk of persistent SIL was associated with continual HPV infection in visits t and t + 1 (HPV positive by Southern blot analysis: odds ratio [OR] = 3.91, and 95% confidence interval [CI] = 1.58-9.65; HPV positive by polymerase chain reaction [PCR]: OR = 2.42, and 95% CI = 1.03-5.67) and a persistent high viral load (OR = 4.07, and 95% CI = 1.35-12.30). When typed by PCR, individuals with type-specific persistent infection in visits t and t + 1, and particularly those with a continual high viral load (OR = 4.97; 95% CI = 1.45-17.02), had the highest risk for persistent SIL compared with those with a low level of type-specific persistent infection or non-type-specific persistent infection. The presence of
Gosvig, Camilla Flarup; Huusom, Lene Drasbek; Andersen, Klaus Kaae
Women with early cervical cancer or intraepithelial neoplasia grades 2 and 3 (CIN2+) are treated by conization; however, they still have a higher risk for subsequent CIN2+ than the general female population. Persistence of high-risk (HR) human papillomavirus (HPV) is a key factor in the development...
Elfgren, Kristina; Elfström, K Miriam; Naucler, Pontus; Arnheim-Dahlström, Lisen; Dillner, Joakim
Introduction of human papillomavirus-based screening is ongoing in many countries, given its higher sensitivity and longer-lasting protection compared with cytology-based screening. However, optimal clinical management of human papillomavirus-positive but cytology-negative women is unclear, and additional studies with clinical follow-up are warranted. The aim of the current study was to investigate the long-term outcomes of the clinical management used in a double-blind, randomized clinical trial of human papillomavirus screening conducted in the context of the routine, organized screening program in Sweden. Among 12,527 women aged 32-38 years enrolled in the trial, we followed up the 195 women who attended the colposcopy screening who were cytologically normal but persistently human papillomavirus positive (at least 12 months later; median, 19 months) in the human papillomavirus testing arm (n = 100) or were randomly selected from the control arm (n = 95). Women in the human papillomavirus testing arm were followed up with repeated human papillomavirus testing, cytologies, and colposcopies if persistently human papillomavirus-positive without cervical intraepithelial neoplasia grade 2 or worse. A similar number of random colposcopies and tests were carried out in the control arm. Women were followed up over 13 years for the main outcome measures: cumulative incidence of cervical intraepithelial neoplasia grade 2 or worse and cervical intraepithelial neoplasia grade 3 or worse. Among women who continued to attend and had continuous human papillomavirus persistence, all (40 of 40, 100% [95% confidence interval, 91-100%]) developed cervical intraepithelial neoplasia grade 2 or worse. There were no cases among women who cleared their human papillomavirus persistence (0 of 35, 0% (95% confidence interval, 0-10%) (P < .001). Among women who had had human papillomavirus persistence but did not continue with repeated human papillomavirus tests (unknown persistence
Nielsen, Ann; Kjaer, Susanne K; Munk, Christian
Persisting human papillomavirus (HPV) infection is a critical step in cervical carcinogenesis. This study was conducted to determine the type-specific HPV persistence and risk factors for persistence of high-risk HPV infections in a large cohort of Danish women. The study was based on a population...
Jensen, Kirsten E; Thomsen, Louise T; Schmiedel, Sven
Some studies suggest that Chlamydia trachomatis (CT) enhances cervical carcinogenesis; however, a possible confounding effect of persistent human papillomavirus (HPV) infection was not addressed. We examined the potential role of CT infection in the development of subsequent cervical intraepithel...... intraepithelial neoplasia grade 3 or worse (CIN3+) in women with prevalent HPV infection and in a subgroup of women with persistent HPV infection....
Vriend, Henrike J.; Bogaards, Johannes A.; van Bergen, Jan E. A. M.; Brink, Antoinette A. T. P.; van den Broek, Ingrid V. F.; Hoebe, Christian J. P. A.; King, Audrey J.; van der Sande, Marianne A. B.; Wolffs, Petra F. G.; de Melker, Hester E.
We assessed whether infection with chlamydia increases the incidence of carcinogenic human papillomavirus (HPV) infections and if HPV persistence is affected by chlamydia co-infection. For 1982 women (16-29 years-old) participating in two consecutive rounds of a chlamydia screening implementation
Adler, David; Wallace, Melissa; Bennie, Thola; Abar, Beau; Sadeghi, Rokhsanna; Meiring, Tracy; Williamson, Anna-Lise; Bekker, Linda-Gail
Persistence of infection with high-risk Human papillomaviruses (HR-HPV) increases the risk of incident and progressive precancerous lesions of the cervix. Rates of HR-HPV persistence have been shown to be increased among HIV-infected adult women, however there is a paucity of literature addressing HPV persistence in the young HIV-infected population. We compared rates of HR-HPV persistence between HIV-infected and HIV-uninfected young women. We obtained self-collected vaginal swabs at six-month intervals from 50 HIV-uninfected and 33 HIV-infected young women recruited through a community youth center (age 17-21 years) and compared rates of HR-HPV persistence. HR-HPV testing was conducted using the Roche's Linear Array® HPV Test. Eighty-three prevalent (upon baseline testing) and incident (upon subsequent testing) individual HR-HPV infections were identified among 43 members of the cohort (23 HIV-uninfected and 20 HIV-infected). At twelve months, 19% of baseline HR-HPV infections continued to be present with a statistically significant difference between HIV-uninfected and HIV-infected participants (4% versus 31%; p=0.01). HIV-infected young women in our cohort had a seven-fold increased rate of persistence of HR-HPV overall at 12 months, indicating an increased risk for incident and progressive precancerous lesions. Identification of persistent infection with HR-HPV may complement cytological findings in determining the need for colposcopy. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Rodríguez, Ana Cecilia; García-Piñeres, Alfonso J; Hildesheim, Allan; Herrero, Rolando; Trivett, Matthew; Williams, Marcus; Atmella, Ivannia; Ramírez, Margarita; Villegas, Maricela; Schiffman, Mark; Burk, Robert; Freer, Enrique; Bonilla, José; Bratti, Concepción; Pinto, Ligia A
We previously reported decreased lymphocyte proliferative responses among older women with persistent human papillomavirus (HPV) infection. To characterize the phenotype of peripheral lymphocytes associated with persistent HPV infection, we evaluated the expression of different cell surface markers in peripheral blood mononuclear cells (PBMCs) from a case-control study within a 10,049-woman population-based cohort study in Guanacaste, Costa Rica. Women in the cohort aged 46 to 74 and with HPV results at their 5th year anniversary visit were considered, and all women (n=87) with persistent HPV infections, all women (n=196) with transient HPV infections and a random sample of HPV DNA-negative women (n=261) frequency-matched to cases on age were selected for this study. A median of 3 years after the case-control matching visit, cervical cells were collected for liquid-based cytology and repeat HPV DNA genotyping. Blood was obtained from which PBMCs were extracted and cryopreserved for immunological phenotyping via flow cytometry. Significant increases in risk of HPV persistence were observed for three marker subsets indicative of immune cell activation/differentiation. Relative risk estimates were 5.4 (95%CI=2.2–13.3) for CD69+CD4+, 2.6 (95%CI=1.2–5.9) for HLADR+CD3+CD4+ and 2.3 (95%CI=1.1–4.7) for CD45RO+CD27−CD8+. A significant decrease in HPV persistence was observed for a subset marker indicative of an immature, undifferentiated memory state CD45RO+CD27+CD4+ (OR=0.36; 95%CI = 0.17–0.76). Adjustment for these markers only partially explained the previously reported association between decreased lymphoproliferative responses and persistent HPV infection. Whether phenotypic alterations observed predispose to HPV persistence or result from it should be the focus of future studies. PMID:20473864
Moscicki, Anna-Barbara; Ma, Yifei; Farhat, Sepideh; Jay, Julie; Hanson, Evelyn; Benningfield, Susanna; Jonte, Janet; Godwin-Medina, Cheryl; Wilson, Robert; Shiboski, Stephen
Anal cancer is more common in women than in men, yet little is known about the natural history of human papillomavirus (HPV) in women. The objective was to examine the natural history of anal HPV in heterosexual women. Young women participating in an HPV cohort study were seen at 4-month intervals for cervical and anal HPV testing. Time to clearance was estimated using the Kaplan-Meier approach; risks for persistence were assessed using Cox regression models. Seventy-five women (mean age, 23.5 ± 4.1 years) who tested positive for anal HPV were followed for a mean of 84.5 ± 44.9 months. By 3 years, 82.5% of anal non-16 high-risk (HR) HPV, 82.6% of low-risk (LR) HPV, and 76.2% of HPV-16 infections had cleared. By 3 years, only 36.4% of women had become negative for all HPV types. In the multivariable model, concurrent cervical HPV-16 (P anal touching during sex (P = .045), recent anal sex (P = .04), and no condom use during anal sex (P = .04) were associated with HPV-16 persistence. Greater number of new sex partners (P = .024) and condom use during vaginal sex (P = .003) were associated with clearance. Similar associations were found for clearance in all HR-HPV infections. Only concomitant cervical HPV was associated with non-16 HR-HPV persistence. The majority of anal HPV infections cleared within 3 years. HPV-16 infections were slower to clear than other HR-HPV infections, consistent with its role in anal cancer. Specific sexual behaviors were associated with persistence, suggesting that education and behavioral interventions may decrease persistence.
Moscicki, Anna-Barbara; Ma, Yifei; Farhat, Sepideh; Jay, Julie; Hanson, Evelyn; Benningfield, Susanna; Jonte, Janet; Godwin-Medina, Cheryl; Wilson, Robert; Shiboski, Stephen
Background. Anal cancer is more common in women than in men, yet little is known about the natural history of human papillomavirus (HPV) in women. The objective was to examine the natural history of anal HPV in heterosexual women. Methods. Young women participating in an HPV cohort study were seen at 4-month intervals for cervical and anal HPV testing. Time to clearance was estimated using the Kaplan-Meier approach; risks for persistence were assessed using Cox regression models. Results. Seventy-five women (mean age, 23.5 ± 4.1 years) who tested positive for anal HPV were followed for a mean of 84.5 ± 44.9 months. By 3 years, 82.5% of anal non-16 high-risk (HR) HPV, 82.6% of low-risk (LR) HPV, and 76.2% of HPV-16 infections had cleared. By 3 years, only 36.4% of women had become negative for all HPV types. In the multivariable model, concurrent cervical HPV-16 (P anal touching during sex (P = .045), recent anal sex (P = .04), and no condom use during anal sex (P = .04) were associated with HPV-16 persistence. Greater number of new sex partners (P = .024) and condom use during vaginal sex (P = .003) were associated with clearance. Similar associations were found for clearance in all HR-HPV infections. Only concomitant cervical HPV was associated with non-16 HR-HPV persistence. Conclusions. The majority of anal HPV infections cleared within 3 years. HPV-16 infections were slower to clear than other HR-HPV infections, consistent with its role in anal cancer. Specific sexual behaviors were associated with persistence, suggesting that education and behavioral interventions may decrease persistence. PMID:24368624
Nielsen, Ann; Kjaer, Susanne K; Munk, Christian
Persisting human papillomavirus (HPV) infection is a critical step in cervical carcinogenesis. This study was conducted to determine the type-specific HPV persistence and risk factors for persistence of high-risk HPV infections in a large cohort of Danish women. The study was based on a population...... high-risk HPV type at both examinations. Overall, 4.2% of the women had persistent HPV infection, accounting for 26.9% of the initially HPV-positive women. HPV 16, HPV 58, and HPV 31, all from species group alpha 9, were the most persistent types; however, other high-risk HPV types that are detected...... rarely in cancer cases were also likely to persist. The number of high-risk HPV types and detection of HPV 16 infection at baseline and ever use of oral contraceptives increased the risk for persistence. The risk factor analyses also showed that use of an intrauterine device decreased the risk...
Kjær, Susanne K; Frederiksen, Kirsten; Plum, Christian Edinger Munk
Infection with high-risk human papillomavirus (HPV) is the main cause of high-grade cervical intraepithelial neoplasia (CIN) and cancer. It has been suggested that information about high-risk HPV type-specific infection might make cervical cancer screening more effective. Persistent HPV infection...... could also be a useful screening marker. We estimated the long-term risk of high-grade CIN after one-time detection of high-risk HPV DNA and after persistent infection with individual high-risk HPV types....
... 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 ...
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 ...
... 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 ...
Harden, Mallory E; Munger, Karl
Human papillomaviruses are small DNA viruses with a tropism for squamous epithelia. A unique aspect of human papillomavirus molecular biology involves dependence on the differentiation status of the host epithelial cell to complete the viral lifecycle. A small group of these viruses are the etiologic agents of several types of human cancers, including oral and anogenital tract carcinomas. This review focuses on the basic molecular biology of human papillomaviruses. Copyright © 2016 Elsevier B.V. All rights reserved.
Haukioja, Anna; Tervahartiala, Taina; Sorsa, Timo; Syrjänen, Stina
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.
Coser, Janaina; Boeira, Thaís da Rocha; Wolf, Jonas Michel; Cerbaro, Kamila; Simon, Daniel; Lunge, Vagner Ricardo
Human papillomavirus (HPV) infection is common in sexually active women and viral persistence may cause intraepithelial lesions and eventually progress to cervical cancer (CC). The present study aimed to investigate epidemiological factors related to HPV infection and to evaluate viral persistence and CC precursor lesions frequencies in women from a city in the countryside of South Brazil. Three hundred women were recruited from a primary public health care clinic. The patients were interviewed and underwent sampling with cervical brushes for HPV-DNA detection/typing by a PCR-based assay and cytological analysis by Pap smear test. HPV was detected in 47 (15.7%) women. HPV infection was significantly associated with young age (<30 years) and low socio-economic status. Seventeen (5.7%) women presented cytological abnormalities, three of them with precursor CC intraepithelial lesions. A subgroup of 79 women had been previously analyzed and thirteen (16.4%) were persistently infected, two with precursor CC intraepithelial lesions and high-risk HPV types infection (both of them without cervical abnormalities in the first exam). In conclusion, HPV infection was associated with young age (<30 years) and low family income; viral persistence was low (16.4%) but related to CC precursor lesions; and HPV-DNA high risk types detection would help to screen CC in the population. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.
Jensen, Kirsten Egebjerg; Schmiedel, Sven; Frederiksen, Kirsten
BACKGROUND: Smoking has been associated with cervical cancer. We examined whether smoking increases the risk for high-grade cervical lesions in women with high-risk human papillomavirus (HPV) infection. METHODS: In a population-based cohort study, 8,656 women underwent a structured interview...... were also conducted. Hazard ratios (HRs) for a diagnosis of cervical intraepithelial neoplasia grade 3 or worse/high-grade squamous intraepithelial lesions or worse (CIN3+) and the corresponding 95% confidence intervals (CIs) were calculated in the 2 groups. RESULTS: Among high-risk HPV positive women......, and subsequently cervical cells were obtained for HPV DNA testing. Women with high-risk HPV infection and no prevalent cervical disease at baseline (n=1,353) were followed through the Pathology Data Bank for cervical lesions for up to 13 years. Separate analyses of women with persistent high-risk HPV infection...
Vriend, Henrike J; Bogaards, Johannes A; van Bergen, Jan E A M; Brink, Antoinette A T P; van den Broek, Ingrid V F; Hoebe, Christian J P A; King, Audrey J; van der Sande, Marianne A B; Wolffs, Petra F G; de Melker, Hester E
We assessed whether infection with chlamydia increases the incidence of carcinogenic human papillomavirus (HPV) infections and if HPV persistence is affected by chlamydia co-infection. For 1982 women (16-29 years-old) participating in two consecutive rounds of a chlamydia screening implementation trial, swabs were polymerase chain reaction tested to detect chlamydia and 14 carcinogenic HPV genotypes. HPV type-specific incidence and persistence rates were stratified for chlamydia positivity at follow-up. Associations were assessed by multilevel logistic regression analyses with correction for sexual risk factors. HPV type-specific incidence ranged from 1.4% to 8.9% and persistence from 22.7% to 59.4% after a median follow-up of 11 months (interquartile range: 11-12). Differences in 1-year HPV persistence rates between chlamydia -infected and noninfected women were less distinct than differences in HPV incidence rates (pooled adjusted odds ratios of 1.17 [95% CI: 0.69-1.96] and 1.84 [95% CI: 1.36-2.47], respectively). The effect of chlamydia co-infection on HPV-infection risk did not significantly differ by HPV genotype. In conclusion, infection with chlamydia increases the risk of infection by carcinogenic HPV types and may enhance persistence of some HPV types. Although these findings could reflect residual confounding through unobserved risk factors, our results do give reason to explore more fully the association between chlamydia and HPV type-specific acquisition and persistence. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Rajendra, Shanmugarajah; Wang, Bin; Pavey, Darren; Sharma, Prateek; Yang, Tao; Lee, Cheok Soon; Gupta, Neil; Ball, Madeleine J; Gill, Raghubinder Singh; Wu, Xiaojuan
We investigated the role of high-risk human papillomavirus (hr-HPV) in patients with Barrett's dysplasia and adenocarcinoma (EAC). Clearance vs persistence of HPV (DNA, E6 or E7 mRNA, and p16INK4A protein) and overexpression or mutation of p53 were determined for 40 patients who underwent endotherapy for Barrett's dysplasia or EAC. After ablation, dysplasia or neoplasia was eradicated in 34 subjects (24 squamous, 10 intestinal metaplasia). Six patients had detectable lesions after treatment; 2 were positive for transcriptionally active hr-HPV, and 4 had overexpression of p53. Before endotherapy, 15 patients had biologically active hr-HPV, 13 cleared the infection with treatment, and dysplasia or EAC was eliminated from 12 patients. One patient who cleared HPV after ablation acquired a p53 mutation, and their cancer progressed. Of 13 patients with overexpression of p53 before treatment, 10 cleared the p53 abnormality after ablation with eradication of dysplasia or neoplasia, whereas 3 of 13 had persistent p53 mutation-associated dysplasia after endotherapy (P = .004). Immunohistochemical and sequence analyses of p53 produced concordant results for 36 of 40 samples (90%). Detection of dysplasia or neoplasia after treatment was associated with HPV persistence or continued p53 overexpression. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
Grabowski, Mary K; Gray, Ronald H; Serwadda, David; Kigozi, Godfrey; Gravitt, Patti E; Nalugoda, Fred; Reynolds, Steven J; Wawer, Maria J; Watya, Stephen; Quinn, Thomas C; Tobian, Aaron A R
High-risk human papillomavirus (HR-HPV) viral load is associated with HR-HPV transmission and HR-HPV persistence in women. It is unknown whether HR-HPV viral load is associated with persistence in HIV-negative or HIV-positive men. HR-HPV viral load and persistence were evaluated among 703 HIV-negative and 233 HIV-positive heterosexual men who participated in a male circumcision trial in Rakai, Uganda. Penile swabs were tested at baseline and 6, 12 and 24 months for HR-HPV using the Roche HPV Linear Array, which provides a semiquantitative measure of HPV shedding by hybridisation band intensity (graded: 1-4). Prevalence risk ratios (PRR) were used to estimate the association between HR-HPV viral load and persistent detection of HR-HPV. HR-HPV genotypes with high viral load (grade:3-4) at baseline were more likely to persist than HR-HPV genotypes with low viral load (grade: 1-2) among HIV-negative men (month 6: adjPRR=1.83, 95% CI 1.32 to 2.52; month 12: adjPRR=2.01, 95% CI 1.42 to 3.11), and HIV-positive men (month 6: adjPRR=1.33, 95% CI 1.06 to 1.67; month 12: adjPRR=1.73, 95% CI 1.18 to 2.54). Long-term persistence of HR-HPV was more frequent among HIV-positive men compared with HIV-negative men (month 24: adjPRR=2.27, 95% CI 1.47 to 3.51). Persistence of newly detected HR-HPV at the 6-month and 12-month visits with high viral load were also more likely to persist to 24 months than HR-HPV with low viral load among HIV-negative men (adjPRR=1.67, 95% CI 0.88 to 3.16). HR-HPV genotypes with high viral load are more likely to persist among HIV-negative and HIV-positive men, though persistence was more common among HIV-positive men overall. The results may explain the association between high HR-HPV viral load and HR-HPV transmission. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Sammarco, Michela L; Del Riccio, Ilenia; Tamburro, Manuela; Grasso, Guido M; Ripabelli, Giancarlo
We examined persistence and clearance of human papillomavirus (HPV) infections and risk factors associated with persistence in 79 women based on the results of two sequential tests performed over 12-24 months. Between February 2008 and August 2009, 398 women aged 18-63 years were examined for presence of cervical HPV infection by cervical scrape specimen and PCR. Detection was performed using Linear Array (LA) HPV Genotyping Test. All women were interviewed, and a short questionnaire was administered to collect information on socio-demographic characteristics, sexual and reproductive history, smoking habits, oral contraceptive use, history of sexually transmitted diseases, and Chlamydia trachomatis or Mycoplasma spp. infections. Pearson's χ² test was used to verify the association between all independent variables with the response variable. Initially, high risk-HPV (HR-HPV) and low risk-HPV (LR-HPV) infection was detected in 69.6% and 30.4% of the women, respectively, whilst multiple infections occurred in 53.2%. HPV 16 was the most common (20.2%) high-risk type, followed by 52, 31 and 53. At follow-up, HR-HPV infection was detected in 50.6% of the women; among these, 67.5% had persistent infection, while 12.5% acquired other high-risk types, and 20.0% of those positive for LR-HPV at entry had a new HR-HPV infection. Multiple infections were detected in 38.0% of the women. HPV 16 and 31 were the most frequent types, followed by HPV 73. Type-specific HR-HPV persistence was found in 49.1% of women. HPV 31, 39 and 73 were the most frequently persistent types, whilst HPV 16 was the least persistent. No significant age difference between women with persistence or clearance was found. The highest HR-HPV persistence occurred in the 22-27 years old group, whereas clearance increased in women aged 28-33 years. No significant association between persistent HR-HPV infection and oral contraceptive use, smoking habits and history of sexually transmitted disease was detected
Hea Young Oh
Full Text Available PURPOSE: This prospective study aimed to examine the combined effect of viral load and alcohol consumption on the risk of persistent high-risk (HR human papillomavirus (HPV infection. METHODS: Among women undergoing health screening between 2002 and 2011 at the National Cancer Center, 284 and 122 women with HR-HPV infection and cytological findings of low-grade squamous intraepithelial or lower-grade lesions were followed up for 1 and 2 years, respectively. Multivariate logistic regression analysis was performed, and the relative excess risk due to interaction (RERI and synergy index (S were calculated. RESULTS: Among drinkers, the risks of 1-year (odds ratio [OR] 4.09, 95% confidence interval [CI] 2.05-8.18 and 2-year persistence (OR 8.08, CI 2.36-27.6 were significantly higher for high HPV loads than for low HPV loads; this association was not seen for non-drinkers. The risks for 1-year (OR 4.14, CI 1.89-9.05 and 2-year persistence (OR 6.61, CI 2.09-20.9 were significantly higher in subjects with a high HPV load who were also drinkers than in those who were non-drinkers. A high HPV load together with a longer drinking duration or higher alcohol consumption was associated with increased risks of 1-year (OR 3.07, CI 1.40-6.75 or OR 2.05, CI 0.87-4.83 and 2-year persistence (OR 6.40, CI 1.72-23.8 or OR 4.14, CI 1.18-14.6. The synergistic effect of alcohol consumption and HR-HPV load was stronger on the risk of 2-year persistence (RERI = 3.26, S = 2.38 than on the risk of 1-year persistence (RERI = 1.21, S = 1.63. CONCLUSIONS: The synergistic effect of HR-HPV load and alcohol consumption was associated with the risk of HR-HPV persistence and was stronger for longer-term HR-HPV infection. Limiting alcohol consumption might be an important measure to prevent the development of cervical cancer in women with a high HR-HPV load.
Nyitray, Alan G; Carvalho da Silva, Roberto J; Chang, Mihyun; Baggio, Maria Luiza; Ingles, Donna J; Abrahamsen, Martha; Papenfuss, Mary; Lin, Hui-Yi; Salmerón, Jorge; Quiterio, Manuel; Lazcano-Ponce, Eduardo; Villa, Luisa L; Giuliano, Anna R
Given high rates of anal disease, we investigated the natural history of high-risk anal human papillomavirus (HPV) among a multinational group of men who have sex with men (MSM) aged 18-64 years. Anal specimens from human immunodeficiency virus-negative men from Brazil, Mexico, and the United States were genotyped. Over 2 years, 406 MSM provided evaluable specimens every 6 months for ≥2 visits. These men were stratified into men who have sex only with men (MSOM, n = 70) and men who have sex with women and men (MSWM, n = 336). Persistence was defined as ≥12 months' type-specific duration and could begin with either a prevalent or incident infection. Prevalence ratios and 95% confidence intervals were calculated by Poisson regression. Median follow-up time was 2.1 years. Retention was 82%. Annual cumulative incidence of 9-valent vaccine types was 19% and 8% among MSOM and MSWM, respectively (log-rank P = .02). Duration of anal HPV did not differ for MSOM and MSWM and was a median of 6.9 months for HPV-16 after combining men from the 2 groups. Among men with prevalent high-risk infection (n = 106), a total of 36.8%, retained the infection for at least 24 months. For those with prevalent HPV-16 (n = 27), 29.6% were persistent for at least 24 months. Persistence of high-risk HPV was associated with number of male anal sex partners and inversely associated with number of female sex partners. MSM with prevalent high-risk HPV infection should be considered at increased risk for nontransient infection. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail firstname.lastname@example.org.
Nyitray, Alan G.; Carvalho da Silva, Roberto J.; Chang, Mihyun; Baggio, Maria Luiza; Ingles, Donna J.; Abrahamsen, Martha; Papenfuss, Mary; Lin, Hui-Yi; Salmerón, Jorge; Quiterio, Manuel; Lazcano-Ponce, Eduardo; Villa, Luisa L.; Giuliano, Anna R.
Background. Given high rates of anal disease, we investigated the natural history of high-risk anal human papillomavirus (HPV) among a multinational group of men who have sex with men (MSM) aged 18–64 years. Methods. Anal specimens from human immunodeficiency virus–negative men from Brazil, Mexico, and the United States were genotyped. Over 2 years, 406 MSM provided evaluable specimens every 6 months for ≥2 visits. These men were stratified into men who have sex only with men (MSOM, n = 70) and men who have sex with women and men (MSWM, n = 336). Persistence was defined as ≥12 months’ type-specific duration and could begin with either a prevalent or incident infection. Prevalence ratios and 95% confidence intervals were calculated by Poisson regression. Results. Median follow-up time was 2.1 years. Retention was 82%. Annual cumulative incidence of 9-valent vaccine types was 19% and 8% among MSOM and MSWM, respectively (log-rank P = .02). Duration of anal HPV did not differ for MSOM and MSWM and was a median of 6.9 months for HPV-16 after combining men from the 2 groups. Among men with prevalent high-risk infection (n = 106), a total of 36.8%, retained the infection for at least 24 months. For those with prevalent HPV-16 (n = 27), 29.6% were persistent for at least 24 months. Persistence of high-risk HPV was associated with number of male anal sex partners and inversely associated with number of female sex partners. Conclusions. MSM with prevalent high-risk HPV infection should be considered at increased risk for nontransient infection. PMID:26962079
Conclusions: HIV-infected young women in our cohort had a seven-fold increased rate of persistence of HR-HPV overall at 12 months, indicating an increased risk for incident and progressive precancerous lesions. Identification of persistent infection with HR-HPV may complement cytological findings in determining the need for colposcopy.
Channa E Schmeink
Full Text Available OBJECTIVE: To evaluate hr-HPV persistence and associated risk factors in a prospective cohort of young unscreened women. Additionally, the relation between hr-HPV status and cytology/histology results is examined. METHODS AND PRINCIPAL FINDINGS: Two year follow-up of 235 out of 2065 young women (18-29 years, participating in a large, one year epidemiological study, with questionnaires, self-collected cervico-vaginal samples (Vibabrush, and SPF(10LiPA for HPV detection. Only women hr-HPV positive at sample month 12 were invited for a second year of follow-up. After study follow-up, available cytology/histology data were requested from PALGA (the national network and registry of histo- and cytopathology in The Netherlands. These data were compared with available cytology/histology data of the month 12 hr-HPV negative women from the same cohort. 44.1% of the hr-HPV types detected at study month 12, persisted during follow-up. HPV types 45, 31, 16 and 18 were most likely to persist with percentages of 60.0%, 56.8%, 54.4%,and 50.0%, respectively. Compared to newly detected infections at month 12, infections present since 6 months or baseline had an increased risk to persist (OR 3.09 [95% CI: 1.74-5.51] and OR 4.99 [95% CI: 2.67-9.32], respectively. Other co-factors influencing persistence were, multiple HPV infections, smoking and multiple lifetime sexual partners. The percentage of women with a HSIL/CIN2+ (12.1% in the persistent HPV group, was not significantly different (p = 0.107 from the 5.3% of the women who cleared the hr-HPV infection, but was significantly (p 0.000 higher than to the 1.6% of women in the hr-HPV negative control group. CONCLUSION: We showed that HPV genotype, multiple infections, smoking, and multiple lifetime sexual partners are co-factors that increase the risk of hr-HPV persistency. Most importantly, we showed that hr-HPV infections are more likely to persist the longer they have been present and that women with a
Taylor, Sylvia; Bunge, Eveline; Bakker, Marina; Castellsagué, Xavier
Human papillomavirus (HPV) vaccines were designed to prevent cervical cancer in women and their provision remains a major public health need. However, HPV is also a major cause of non-cervical anogenital and oropharyngeal cancers and the potential benefit of vaccination likely extends beyond cervical cancer. A systematic literature search of PubMed (1995-2014) identified publications assessing the incidence, persistence, and clearance of non-cervical anogenital/oral HPV infections. Comparability with cervical HPV was assessed by identifying articles assessing the same or similar populations. Available data suggest high incidence rates of non-cervical HPV infection in men and women, with HPV-16 predominating in all sites. The incidence of high risk HPV per 100 person-years ranged from 11.4 to 72.9 for penile infections, 6.7-47.9 at other male genital sites, and 4.4-36.7 and 5.3-23.4 for anal infections in men and women, respectively. The incidence per 100 person-years of oral infection with any HPV type ranged from 5.7 to 6.7 in men and 6.8-39.6 in women. Within the limitations of the data, there was a general pattern of higher incidence and clearance of non-cervical genital HPV infections, compared to cervical infections. HIV status, circumcision, number of sex partners and partner HPV status significantly influenced high-risk HPV incidence/clearance at male anogenital sites. Few studies assessed risk factors for oral HPV. Parallels appear to exist between the epidemiology of cervical and non-cervical HPV infections in terms of incidence, HPV-type distribution, and risk factors for infection. Available data suggest that non-cervical genital HPV infections may occur more frequently, with higher clearance rates, than cervical infections. More extensive studies could provide useful information for estimating vaccine impact, the wider cost-benefit of HPV vaccination, and guiding vaccination policy. Not applicable, as systematic review of the literature.
Angela RI Meyrelles
Full Text Available This study investigated the rate of human papillomavirus (HPV persistence, associated risk factors, and predictors of cytological alteration outcomes in a cohort of human immunodeficiency virus-infected pregnant women over an 18-month period. HPV was typed through L1 gene sequencing in cervical smears collected during gestation and at 12 months after delivery. Outcomes were defined as nonpersistence (clearance of the HPV in the 2nd sample, re-infection (detection of different types of HPV in the 2 samples, and type-specific HPV persistence (the same HPV type found in both samples. An unfavourable cytological outcome was considered when the second exam showed progression to squamous intraepithelial lesion or high squamous intraepithelial lesion. Ninety patients were studied. HPV DNA persistence occurred in 50% of the cases composed of type-specific persistence (30% or re-infection (20%. A low CD4+T-cell count at entry was a risk factor for type-specific, re-infection, or HPV DNA persistence. The odds ratio (OR was almost three times higher in the type-specific group when compared with the re-infection group (OR = 2.8; 95% confidence interval: 0.43-22.79. Our findings show that bonafide (type-specific HPV persistence is a stronger predictor for the development of cytological abnormalities, highlighting the need for HPV typing as opposed to HPV DNA testing in the clinical setting.
D'Hauwers, K.W.M.; Tjalma, W.A.
Persistent infection with high-risk Human papillomavirus (hr-HPV 16, 18, 31, 33, and 45) is the main risk factor for developing malignant genital lesions. Screening methods and follow-up schedules for cervical cancer are well known. A golden standard to screen and monitor men does not exist yet,
Full Text Available Human papillomavirus (HPV is one of the most common sexually transmitted infections world-wide. Low-risk HPV-types are associated with genital warts. Persistent infection with high-risk HPV-types is associated with genital cancers. Smoking and HIV infection have consistently been associated with longer duration of HPV infection and risk for genital cancer. There is an increasing incidence of anal cancers, and a close association with HPV infection has been demonstrated. Receptive anal sex and HIV-positive status are associated with a high risk for anal cancer. Two HPV vaccines are now available and offer protection from infection by the HPV-types included in the vaccine. This benefit is maximally seen in young women who were uninfected prior to vaccination.
Xi, Long Fu; Schiffman, Mark; Koutsky, Laura A; Hughes, James P; Hulbert, Ayaka; Shen, Zhenping; Galloway, Denise A; Kiviat, Nancy B
In our previous study of the etiologic role of oncogenic human papillomavirus (HPV) types other than HPV16 and 18, we observed a significantly higher risk of cervical intraepithelial neoplasia Grades 2-3 (CIN2/3) associated with certain lineages of HPV types 31/33/45/56/58 [called high-risk (HR) variants] compared with non-HR variants. This study was to examine whether these intra-type variants differ in persistence of the infection and persistence-associated risk of CIN2/3. Study subjects were women who had any of HPV types 31/33/45/56/58 newly detected during a 2-year follow-up with 6-month intervals. For each type, the first positive sample was used for variant characterization. The association of reverting-to-negativity with group of the variants and CIN2/3 with length of positivity was assessed using discrete Cox regression and logistic regression, respectively. Of the 598 newly detected, type-specific HPV infections, 312 became undetectable during follow-up. Infections with HR, compared with non-HR, variants were marginally more likely to become negative [adjusted hazard ratio = 1.3; 95% confidence interval (CI), 0.9-1.8]. The adjusted odds ratio associating with the development of CIN2/3 was 3.0 (95% CI, 1.2-7.4) for persistent infections with HR variants for 6 months and 10.0 (95% CI, 3.8-38.0) for persistent infections with HR variants for 12-18 months as compared with the first positive detection of HR variants. Among women with non-HR variants, there were no appreciable differences in risk of CIN2/3 by length of positivity. Findings suggest that the lineage-associated risk of CIN2/3 was not mediated through a prolonged persistent infection, but oncogenic heterogeneity of the variants. © 2016 UICC.
de Pokomandy, Alexandra; Kaufman, Elaina; de Castro, Christina; Mayrand, Marie-Hélène; Burchell, Ann N; Klein, Marina; Charest, Louise; Auger, Manon; Rodrigues-Coutlée, Sophie; Coutlée, François
The risk of anal cancer due to high-risk human papillomavirus (HR-HPV) is higher in women living with human immunodeficiency virus (HIV) than in the general population. We present findings of cervical and anal HPV and cytologic tests at baseline in the EVVA cohort study and HPV persistence data 6 months after baseline. Semiannual visits included questionnaires, chart reviews, cervical/anal cytologic and cervical/anal HPV testing for 2 years. Genotyping for 36 HPV genotypes was performed using the Roche Linear Array HPV genotyping test. A total of 151 women living with HIV were recruited. At baseline, 75% had anal HPV, 51% had anal HR-HPV, 50% had cervical HPV, and 29% had cervical HR-HPV. Anal HPV-16 and HPV-51 were more frequent in women born in Canada (31% and 29%, respectively, compared with ≤16% for other women). Most anal HR-HPV types detected at 6 months (57%-93%) were persistent from baseline. Findings of anal cytologic tests were abnormal for 37% of women. Anal HPV is highly prevalent in women living with HIV, and type distribution varies by place of birth. High-resolution anoscopy was indicated in more than one third of results. As anal cancer is potentially preventable, these important findings need to be considered when selecting the best approach for anal cancer screening programs.
Full Text Available The aim of this paper was to present the role of human papillomavirus (HPV in cervical carcinogenesis from several aspects. By explaining the HPV virus lifecycle and structure, its effect on cervical cell cycle and subversion of immune response can be better understood. Early E region of the viral genome encodes proteins that are directly involved in carcinogenesis. The E6 protein binds to p53 protein (product of tumor-suppressor gene blocking and degrading it, which in turn prevents cell cycle arrest and apoptosis induction. E6 is also capable of telomerase activation, which leads to cell immortalization; it also reacts with host proto-oncogene c-jun, responsible for transcription, shortens G1 phase and speeds up the transition from G1 to S phase of the cells infected by HPV. E7 forms bonds with retinoblastoma protein (product of tumor-suppressor gene and inactivates it. It can inactivate cyclin inhibitors p21, p27, and abrogate the mitotic spindle checkpoint with the loss of protective effect of pRB and p53. The immune system cannot initiate early immunological reaction since the virus is non-lytic, while the concentration of viral proteins - antigens is low and has a basal intracellular position. Presentation through Langerhans cells (LC is weak, because the number of these cells is low due to the effect of HPV. E7 HPV reduces the expression of E-cadherin, which is responsible for LC adhesion to HPVtransformed keratinocytes. Based on these considerations, it may be concluded that the process of cervical carcinogenesis includes viral, genetic, cellular, molecular-biological, endocrine, exocrine and immunological factors.
Ma, Barbara; Maraj, Bharat; Tran, Nam Phuong; Knoff, Jayne; Chen, Alexander; Alvarez, Ronald D; Hung, Chien-Fu; Wu, T.-C.
Introduction Identification of human papillomavirus (HPV) as the etiologic factor of cervical, anogenital, and a subset of head and neck cancers has stimulated the development of preventive and therapeutic HPV vaccines to control HPV-associated malignancies. Excitement has been generated by the commercialization of two preventive L1-based vaccines, which use HPV virus-like particles (VLPs) to generate capsid-specific neutralizing antibodies. However, factors such as high cost and requirement for cold chain have prevented widespread implementation where they are needed most. Areas covered Next generation preventive HPV vaccine candidates have focused on cost-effective stable alternatives and generating broader protection via targeting multivalent L1 VLPs, L2 capsid protein, and chimeric L1/L2 VLPs. Therapeutic HPV vaccine candidates have focused on enhancing T cell-mediated killing of HPV-transformed tumor cells, which constitutively express HPV-encoded proteins, E6 and E7. Several therapeutic HPV vaccines are in clinical trials. Expert opinion Although progress is being made, cost remains an issue inhibiting the use of preventive HPV vaccines in countries that carry the majority of the cervical cancer burden. In addition, progression of therapeutic HPV vaccines through clinical trials may require combination strategies employing different therapeutic modalities. As research in the development of HPV vaccines continues, we may generate effective strategies to control HPV-associated malignancies. PMID:23163511
Human papillomavirus causes viral-dependent cancers, including cervical, anal, vulvar, penile, vaginal, and oropharyngeal, and condyloma acuminata. In the last decade, HPV prophylactic vaccine has been developed and spread worldwide after many large-scale clinical studies. These studies demonstrate significant clinical efficacy for prevention of HPV16/18/6/11-related diseases. In particular, prevention of cervical cancer should be the most important role in the world. In Japan, incidence of cervical cancer does not increase, but the peak of age of the patients at 2005 is 25-45 years old and became 20 years younger than that at 1985. The current two HPV vaccines can prevent the infection of HPV16/18 among high-risk HPVs and will provide a significant impact especially on young-age onset cervical cancer. Furthermore, quadrivalent HPV vaccine, Gardasil, has shown population impact that is decrease of patients with condyloma acuminate in several countries. The clinical efficacy seems to be convincing. Here HPV vaccine will be reviewed based on the literatures.
... 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 ...
Rebolj, Matejka; Preisler, Sarah; Ejegod, Ditte Møller
We aimed to determine the disagreement in primary cervical screening between four human papillomavirus assays: Hybrid Capture 2, cobas, CLART, and APTIMA. Material from 5,064 SurePath samples of women participating in routine cervical screening in Copenhagen, Denmark, was tested with the four...... of considerable disagreement between human papillomavirus assays. This suggested that the extent of disagreement in primary screening is neither population- nor storage media-specific, leaving assay design differences as the most probable cause. The substantially different selection of women testing positive...... on the various human papillomavirus assays represents an unexpected challenge for the choice of an assay in primary cervical screening, and for follow up of in particular HPV positive/cytology normal women....
Campbell, Christine M. Pierce; Kreimer, Aimée R.; Lin, Hui-Yi; Fulp, William; O’Keefe, Michael T.; Ingles, Donna J.; Abrahamsen, Martha; Villa, Luisa L.; Lazcano-Ponce, Eduardo; Giuliano, Anna R.
Persistent infection with oral HPV16 is believed to drive the development of most oropharyngeal cancers. However, patterns of oral HPV16 persistence remain understudied, particularly among HIV-negative individuals. Oral HPV16 persistence was evaluated among 1626 participants of the HPV Infection in Men (HIM) Study. Twenty-three oral HPV16-positive men who provided an oral gargle sample on ≥2 study visits were included in the analysis. Archived oral samples from all follow-up visits were tested for HPV16 using Linear Array and INNO-LiPA detection methods. Persistence was evaluated using consecutive HPV16-positive visits held approximately 6 months apart and using the Kaplan-Meier method. Oral HPV16-positive men were aged 18–64 years (median, 36 years; IQR, 25–42) and were followed for a median of 44.4 months (IQR, 29.9–49.5). Of 13 incident infections, 4 (30.8%) persisted ≥12 months, 1 (10.0%) persisted ≥24 months, and none persisted ≥36 months (median infection duration, 7.3 months [95% CI, 6.4–NA]). Of 10 prevalent infections, 9 (90.0%) persisted ≥12 months, 8 (80.0%) persisted ≥24 months, 4 (57.1%) persisted ≥36 months, and 2 (40.0%) persisted ≥48 months (median infection duration, NA). Twelve-month persistence of incident infections increased significantly with age (P trend=0.028). Prevalent oral HPV16 infections in men persisted longer than newly acquired infections, and persistence appeared to increase with age. These findings may explain the high prevalence of oral HPV observed at older ages. Understanding oral HPV16 persistence will aid in the identification of men at high-risk of developing HPV-related oropharyngeal cancer. PMID:25575501
Mendoza-Pinto, C; García-Carrasco, M; Vallejo-Ruiz, V; Méndez-Martínez, S; Taboada-Cole, A; Etchegaray-Morales, I; Muñóz-Guarneros, M; Reyes-Leyva, J; López-Colombo, A
Objectives Our objective was to study the incidence, persistence and clearance of human papillomavirus infection in systemic lupus erythematosus women and assess risk factors for persistence of human papillomavirus infection. Methods We carried out a prospective, observational cohort study of 127 systemic lupus erythematosus women. Patients were evaluated at baseline and at three years. Traditional and systemic lupus erythematosus women-related disease risk factors were collected. Gynaecological evaluations and cervical cytology screening were made. Human papillomavirus detection and genotyping were made by polymerase chain reaction and linear array. Results The cumulative prevalence of human papillomavirus infection increased from 22.8% at baseline to 33.8% at three years; p = human papillomavirus infection was 10.1 per 1000 patient-months. At three years, 47 (88.6%) prevalent infections were cleared. Independent risk factors associated with incident human papillomavirus infection included more lifetime sexual partners (odds ratio = 1.8, 95% confidence interval = 1.11-3.0) and cumulative cyclophosphamide dose (odds ratio = 3.9, 95% confidence interval = 1.2-12.8). Conclusions In systemic lupus erythematosus women, the cumulative prevalence of human papillomavirus infection, including high risk-human papillomavirus and multiple human papillomavirus infections, may increase over time. Most persistent infections were low risk-human papillomavirus. The number of lifetime sexual partners and the cumulative cyclophosphamide dose were independently associated with incident human papillomavirus infection.
Cornall, Alyssa M; Roberts, Jennifer M; Molano, Monica; Machalek, Dorothy A; Phillips, Samuel; Hillman, Richard J; Grulich, Andrew E; Jin, Fengyi; Poynten, I Mary; Templeton, David J; Garland, Suzanne M; Tabrizi, Sepehr N
Introduction Anal squamous cell carcinoma is preceded by persistent infection with high-risk human papillomavirus (HPV) and the cancer precursor, high-grade squamous intraepithelial lesion (HSIL). Detection of specific HPV genotypes and HPV-related biomarkers may be an option for primary anal screening. However, more data on the natural history of HPV-related anal lesions are required. The outcomes from this study will enhance our understanding of the clinical and biological behaviour of HPV-related anal lesions and inform the development of future HPV genotype and/or biomarker screening tests. Methods and analysis HIV-negative and HIV-positive men who have sex with men, aged 35 years and over, recruited from community-based settings in Sydney, Australia, attend 6 clinic visits over 3 years. At the first 5 visits, participants undergo a digital anorectal examination, an anal swab for HPV genotyping and anal cytology, and high-resolution anoscopy with directed biopsy of any visible abnormalities that are suggestive of any abnormality suspicious of SIL. Tissue sections from participants diagnosed with histologically confirmed HSIL at the baseline clinic visit will undergo laser capture microdissection, HPV detection and genotyping, and quantitation of CpG methylation in baseline and follow-up biopsies. Histological and cytological findings in combination with HPV genotyping data will be used to identify persistent HSIL. HSIL will be stratified as non-persistent and persistent based on their status at 12 months. The performance of HPV genotype and methylation status in predicting disease persistence at 12 months will be assessed, along with associations with HIV status and other covariates such as age. Ethics and dissemination The St Vincent's Hospital Ethics Committee granted ethics approval for the study. Written informed consent is obtained from all individuals before any study-specific procedures are performed. Findings from this study will be disseminated
Josiassen, Michael; Larsen, Christian Grønhøj; Lajer, Christel Bræmer
The prevalence of oropharyngeal cancer is increasing in the Western world, and human papillomavirus (HPV) is believed to play a role in this development. Patients with HPV-positive oropharyngeal cancer differ significantly from patients with HPV-negative cancer. They may present solely with a small...
Jensen, K E; Schmiedel, S; Norrild, B
BACKGROUND:Several environmental factors have been associated with increased risks for cervical cancer. We examined whether reproductive history, contraceptive use, or sexual behaviour increase the risk for cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among women with persistent...
... 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 ...
Oakeshott, Pippa; Aghaizu, Adamma; Reid, Fiona; Howell-Jones, Rebecca; Hay, Phillip E; Sadiq, S Tariq; Lacey, Charles J; Beddows, Simon; Soldan, Kate
To investigate frequency and risk factors for prevalent, incident, and persistent carcinogenic human papillomavirus (HPV) in young women before the introduction of immunisation against HPV types 16 and 18 for schoolgirls. Cohort study 20 London universities and further education colleges. 2185 sexually active female students, mean age 21 years (range 16-27), 38% from ethnic minorities, who took part in the POPI (prevention of pelvic infection) chlamydia screening trial in 2004-08 and who provided duplicate, self taken vaginal swabs and completed questionnaires at baseline. At follow-up, a median of 16 months later, 821 women (38%) returned repeat vaginal swabs by post. In 2009-10, stored samples were tested for HPV. Samples from 404/2185 (18.5% (95% CI 16.9% to 20.2%)) of the cohort were positive for carcinogenic HPV at baseline, including 15.0% (327) positive for non-vaccine carcinogenic genotypes. Reporting two or more sexual partners in the previous year and concurrent Chlamydia trachomatis or bacterial vaginosis were independent risk factors for prevalent vaginal HPV infection. Infection with one or more new HPV types was found in 17.7% (145/821) of follow-up samples, giving an estimated annual incidence of carcinogenic HPV infection of 12.9% (95% CI 11.0% to 15.0%). Incident infection was more common in women reporting two or more partners in the previous year, agedcarcinogenic HPV infection, 20 (14% (8.3% to 19.7%) had infection with the same carcinogenic HPV type(s) detected after 12-28 months. Of these women, 13 (65%) had redetected infection with HPV 16 or 18, and nine (45%) with non-vaccine carcinogenic HPV genotypes. In the first UK cohort study of carcinogenic HPV in young women in the community, multiple sexual partners was an independent predictor of both prevalent and incident infection. Infection with non-vaccine carcinogenic genotypes was common. Although current HPV vaccines offer partial cross protection against some non-vaccine carcinogenic HPV
There is growing evidence of a significant burden of human papillomavirus (HPV) infection and associated disease in men. High rates of HPV infection have been observed in men from sub-Saharan Africa where HIV prevalence is high. HIV infection increases HPV prevalence, incidence and persistence and is strongly ...
Infection with Human papillomavirus (HPV) contributes to malignant changes in the cervix leading to cancer mortality among women. HPV vaccine is now available for its prevention, yet the level of uptake is low. The study aimed at determining Perception, Acceptance and Uptake of Human papillomavirus Vaccine among ...
Burger, M. P. M.; Hollema, H.; Gouw, A. S. H.; Pieters, W. J. L. M.; Quint, W. G. V.
Objective-To assess the relation between two risk factors for cervical neoplasia: smoking and infection with oncogenic human papillomavirus. It has been suggested that smoking causes a local immunological defect, which could facilitate the infection and persistence of human papillomavirus.
Burger, M. P.; Hollema, H.; Gouw, A. S.; Pieters, W. J.; Quint, W. G.
OBJECTIVE: To assess the relation between two risk factors for cervical neoplasia: smoking and infection with oncogenic human papillomavirus. It has been suggested that smoking causes a local immunological defect, which could facilitate the infection and persistence of human papillomavirus. DESIGN:
Bart Tummers; van der Burg, Sjoerd H
Persistent infections with a high-risk type human papillomavirus (hrHPV) can progress to cancer. High-risk HPVs infect keratinocytes (KCs) and successfully suppress host immunity for up to two years despite the fact that KCs are well equipped to detect and initiate immune responses to invading pathogens. Viral persistence is achieved by active interference with KCs innate and adaptive immune mechanisms. To this end hrHPV utilizes proteins encoded by its viral genome, as well as exploits cellu...
Johannsen, Eric [Department of Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706 (United States); Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706 (United States); McArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706 (United States); Lambert, Paul F., E-mail: email@example.com [Department of Oncology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706 (United States); McArdle Laboratory for Cancer Research, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706 (United States)
Human papilllomaviruses (HPVs) are common human pathogens that infect cutaneous or mucosal epithelia in which they cause warts, self-contained benign lesions that commonly regress. The HPV life cycle is intricately tied to the differentiation of the host epithelium it infects. Mucosotropic HPVs are the most common sexually transmitted pathogen known to mankind. A subset of the mucosotropic HPVs, so-called high risk HPVs, is etiologically associated with numerous cancers of the anogenital tract, most notably the cervix, as well as a growing fraction of head and neck cancers. In these cancers, the HPV genome, which normally exists an a double stranded, circular, nuclear plasmid, is commonly found integrated into the host genome and expresses two viral oncogenes, E6 and E7, that are implicated in the development and maintainance of the cancers caused by these high risk HPVs. Numerous studies, primarily on the high risk HPV16, have documented that the methylation status of the viral genome changes not only in the context of the viral life cycle but also in the context of the progressive neoplastic disease that culminates in cancer. In this article, we summarize the knowledge gained from those studies. We also provide the first analysis of available ChIP-seq data on the occupancy of both epigentically modified histones as well as transcription factors on the high risk HPV18 genome in the context of HeLa cells, a cervical cancer-derived cell line that has been the subject of extensive analyses using this technique. - Highlights: • Methylation status of HPV genomes is dynamic. • Changes are seen in both the viral life cycle and neoplasia. • Histone modification status at LCR is predictive of transcription factor occupancy. • Novel transcription factor binding noted by ChIP-seq.
This page contains brief information about recombinant human papillomavirus (HPV) nonavalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.
This page contains brief information about recombinant human papillomavirus (HPV) quadrivalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.
This page contains brief information about recombinant human papillomavirus (HPV) bivalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.
Full Text Available ... V.E. parents for prevention publications schedules & records support statements vaccine initiative vaccine safety about bucking the ... GETVAXED.ORG cme Immunizations HPV (Human Papillomavirus) One family's struggles with HPV We provide this video in ...
Full Text Available ... sq how to do kids infect kids links & resources M.O.V.E. parents for prevention ... go to GETVAXED.ORG cme Immunizations HPV (Human Papillomavirus) One family's struggles with HPV We provide ...
Full Text Available ... GETVAXED print ads go to GETVAXED.ORG cme Immunizations HPV (Human Papillomavirus) One family's struggles with HPV ... not possible without a visit to your doctor. Immunizations stop disease from spreading. Check with your family ...
Egawa, Nagayasu; Griffin, Heather; Kranjec, Christian; Murakami, Isao
Summary Human papillomaviruses (HPVs) have evolved over millions of years to propagate themselves in a range of different animal species including humans. Viruses that have co‐evolved slowly in this way typically cause chronic inapparent infections, with virion production in the absence of apparent disease. This is the case for many Beta and Gamma HPV types. The Alpha papillomavirus types have however evolved immunoevasion strategies that allow them to cause persistent visible papillomas. These viruses activate the cell cycle as the infected epithelial cell differentiates in order to create a replication competent environment that allows viral genome amplification and packaging into infectious particles. This is mediated by the viral E6, E7, and E5 proteins. High‐risk E6 and E7 proteins differ from their low‐risk counterparts however in being able to drive cell cycle entry in the upper epithelial layers and also to stimulate cell proliferation in the basal and parabasal layers. Deregulated expression of these cell cycle regulators underlies neoplasia and the eventual progression to cancer in individuals who cannot resolve high‐risk HPV infection. Most work to date has focused on the study of high‐risk HPV types such as HPV 16 and 18, which has led to an understanding of the molecular pathways subverted by these viruses. Such approaches will lead to the development of better strategies for disease treatment, including targeted antivirals and immunotherapeutics. Priorities are now focused toward understanding HPV neoplasias at sites other than the cervix (e.g. tonsils, other transformation zones) and toward understanding the mechanisms by which low‐risk HPV types can sometimes give rise to papillomatosis and under certain situations even cancers. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25752814
Bristol, Molly L; Das, Dipon; Morgan, Iain M
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.
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
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.
Swan David C
Full Text Available Abstract Background There is evidence to suggest that human papillomavirus (HPV can cross the placenta resulting in in-utero transmission. The goal of this study was to determine if HPV can be detected in amniotic fluid from women with intact amniotic membranes. Methods Residual amniotic fluid and cultured cell pellets from amniocentesis performed for prenatal diagnosis were used. PGMY09/11 L1 consensus primers and GP5+/GP6+ primers were used in a nested polymerase chain reaction assay for HPV. Results There were 146 paired samples from 142 women representing 139 singleton pregnancies, 2 twin pregnancies, and 1 triplet pregnancy. The women were 78% Caucasian, 5% African American, 14% Asian, and 2% Hispanic. The average age was 35.2 years with a range of 23–55 years. All samples were β-globin positive. HPV was not detected in any of the paired samples. Conclusion Given the age range, race, and ethnicity of the study population, one would anticipate some evidence of HPV if it could easily cross the placenta, but there was none.
Vivian C. Nanagas MD, MSc
Full Text Available Objective. To determine male vaccination rates with quadrivalent human papillomavirus vaccine (HPV4 before and after the October 2011 national recommendation to routinely immunize adolescent males. Methods. We reviewed HPV4 dose 1 (HPV4-1 uptake in 292 adolescent males in our urban clinic prior to national recommendations and followed-up for HPV4 series completion rates. After national recommendation, 248 urban clinic and 247 suburban clinic males were reviewed for HPV4-1 uptake. Factors associated with HPV4-1 refusal were determined with multiple logistic regression. Results. Of the initial 292 males, 78% received HPV4-1 and 38% received the 3-dose series. After recommendation, HPV4-1 uptake was 59% and 7% in urban and suburban clinics, respectively. Variables associated with HPV4-1 uptake/refusal included time period, race, type of insurance, and receipt of concurrent vaccines. Conclusions. HPV4-1 vaccination rates in our urban clinic were high before and after routine HPV vaccine recommendations for adolescent males. Our vaccination rates were much higher than in a suburban practice.
Human papillomaviruses (HPVs) infect squamous epithelia and can induce hyperproliferative lesions. More than 120 different HPV types have been characterized and classified into five different genera. While mucosal high-risk HPVs have a well-established causal role in anogenital carcinogenesis, the biology of cutaneous HPVs is less well understood. The clinical relevance of genus beta-PV infection has clearly been demonstrated in patients suffering from epidermodysplasia verruciformis (EV), a rare inherited disease associated with ahigh rate of skin cancer. In the normal population genus beta-PV are suspected to have an etiologic role in skin carcinogenesis as well but this is still controversially discussed. Their oncogenic potency has been investigated in mouse models and in vitro. In 2009, the International Agency for Research on Cancer (IARC) classified the genus beta HPV types 5 and 8 as "possible carcinogenic" biological agents (group 2B) in EV disease. This chapter will give an overview on the knowns and unknowns of infections with genus beta-PV and discuss their potential impact on skin carcinogenesis in the general population.
... in its entirety from the CDC HPV (Human Papillomavirus) Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... hpv.html . CDC review information for HPV (Human Papillomavirus) VIS: Page last reviewed: December 2, 2016 Page ...
(1) Globally, papillomavirus infections are very widespread in the general population worldwide. More than 100 genotypes of human papillomavirus (HPV) have been identified; they differ in targeted tissue and carcinogenic activity. (2) This article describes the clinical manifestations, prevalence and modes of transmission of human papillomavirus infections, and the role of HPV in human cancer. A systematic literature review was carried out to answer these questions based on methods developed by Prescrire. (3) The most frequent clinical manifestations of human papillomavirus infection are cutaneous and anogenital growths such as warts, papillomata and condylomata. The HPV genotypes linked to skin infections differ from those infecting the anogenital area. Genotypes HPV-16 and HPV-18 are frequently associated with high-grade cervical dysplasia. (4) The frequency of HPV infections varies widely from one population to another. HPV (usually genotype 16) is found in 1.5% to 44% of cervical smears. In the 1990s, 25% of women between 20 and 29 years of age in the United States were seropositive for HPV-16. (5) Papillomavirus is highly persistent in the environment, on contaminated objects, linen, floors. Skin infections can occur through indirect or direct contact. Most anogenital infections are sexually transmitted. (6) Most papillomavirus infections are asymptomatic, latent or transient. Various factors, especially immunosuppression, increase the persistence and severity of infections, and can promote progression to cancer. (7) The DNA of some highly carcinogenic HPV genotypes (especially HPV-16 and HPV-18) is present in 95% to 100% of cervical epidermoid tumours. Malignant transformation of lesions due to HPV seems to be facilitated by HPV persistence, a high HPV viral load in the cervix, and immunosuppression. (8) However, HPV infection rarely leads to progression to cancer. Only a minority of infections persist for several years, and only about 10% of low
Full Text Available Abstract Human Papillomavirus vaccines are widely hailed as a sweeping pharmaceutical innovation for the universal benefit of all women. The implementation of the vaccines, however, is far from universal or equitable. Socio-economically marginalized women in emerging and developing, and many advanced economies alike, suffer a disproportionately large burden of cervical cancer. Despite the marketing of Human Papillomavirus vaccines as the solution to cervical cancer, the market authorization (licensing of the vaccines has not translated into universal equitable access. Vaccine implementation for vulnerable girls and women faces multiple barriers that include high vaccine costs, inadequate delivery infrastructure, and lack of community engagement to generate awareness about cervical cancer and early screening tools. For Human Papillomavirus vaccines to work as a public health solution, the quality-assured delivery of cheaper vaccines must be integrated with strengthened capacity for community-based health education and screening.
Olesen, Tina Bech; Svahn, Malene Frøsig; Faber, Mette Tuxen
HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer.......HPV is a common sexually transmitted infection and is considered to be a necessary cause of cervical cancer. The anatomical proximity to the cervix has led researchers to investigate whether Human Papillomavirus (HPV) has a role in the etiology of endometrial cancer....
Walvik, Lena; Svensson, Amanda Björk; Friborg, Jeppe
There is emerging evidence of the association between human papillomavirus and a subset of head and neck cancers. However, the role of human papillomavirus as a causal factor is still debated. This review addresses the association between human papillomavirus and oropharyngeal squamous cell...... carcinoma using the Bradford Hill criteria. The strength of the association is supported by, detection of human papillomavirus infection and antibodies prior to oropharyngeal squamous cell carcinoma. This is furthermore reinforced by the absence of human papillomavirus DNA in healthy tonsils....... The association is geographically consistent throughout the economically developed world. The presence and integration of high-risk human papillomavirus genome in tonsillar tumours, and expression of viral oncogenes, are specific and plausible. Analogous to human papillomavirus in cervical cancer, the rising...
Goodrum, Felicia; Caviness, Katie; Zagallo, Patricia
Viral persistence is the rule following infection with all herpesviruses. The β-herpesvirus, human cytomegalovirus (HCMV), persists through chronic and latent states of infection. Both the chronic and latent states of infection contribute to HCMV persistence and to the high HCMV seroprevalence worldwide. The chronic infection is poorly defined molecularly, but clinically manifests as low-level virus shedding over extended periods of time and often in the absence of symptoms. Latency requires ...
Lazo, P A; Gallego, M I; Ballester, S; Feduchi, E
The integration sites in the cellular genome of human papillomavirus are located in chromosomal regions always associated with oncogenes or other known tumor phenotypes. Two regions, 8q24 and 12q13, are common to several cases of cervical carcinoma and can have integrated more than one type of papillomavirus DNA. These two chromosomal regions contain several genes implicated in oncogenesis. These observations strongly imply that viral integration sites of DNA tumor viruses can be used as the access point to chromosomal regions where genes implicated in the tumor phenotype are located, a situation similar to that of non-transforming retroviruses.
Full Text Available ... school health clinical trials disclosing to kids estate planning find a doctor find health information helpful articles ... sq how to do kids infect kids links & resources M.O.V.E. parents for prevention ... go to GETVAXED.ORG cme Immunizations HPV (Human Papillomavirus) One family's struggles with HPV We provide ...
Lenselink, C.H.; Gerrits, M.M.; Melchers, W.J.G.; Massuger, L.F.A.G.; Hamont, D. van; Bekkers, R.L.M.
OBJECTIVE: To determine whether parents would accept Human Papillomavirus (HPV) vaccination for their children and which variables may influence their decision, including knowledge about cervical cancer and HPV. STUDY DESIGN: Three hundred and fifty-six parents of children aged 10-12 years were
Background. Genital human papillomavirus (HPV) infection is the most common sexually transmitted viral disease in the world. HPV infection of the genital epithelium is associated with genital warts and malignancies of the lower genital tract. Objectives. To describe the distribution, phenotypic appearance and HPV type ...
Cervical cancer is a leading cause of cancer-related deaths among women in India. Human papillomavirus (HPV) infection is the causative agent of cervical cancer; and infection with the high-risk genotypes, predominantly HPV16 and 18, is the biggest risk factor. Vaccines targeting HPV16 and 18 have been found to confer ...
Aug 9, 2010 ... Home; Journals; Journal of Biosciences; Volume 35; Issue 3. Commentary: Human papillomavirus and tar hypothesis for squamous cell cervical cancer. Christina Bennett Allen E Kuhn Harry W Haverkos. Volume 35 Issue 3 September 2010 pp 331-337 ...
Introduction: cervical cancer is the leading cause of cancer deaths among females in Angola and human papillomavirus (HPV) is the main risk factor for the development of pre-cancerous squamous intraepithelial lesions. The diversity and frequency of HPV types in Angola has yet to be reported. Aim: to determine the ...
A series of 10 oesophageal and 10 laryngeal squamous carcinomas was examined by means of immuno cytochemistry and in situ DNA hybridisation to demonstrate human papillomavirus (HPV) infection. Changes in the epithelium adjacent to the carcinoma were found in 5 of 10 oesophageal and 7 of 10 laryngeal ...
Benevides dos Santos, Paulo José; Borborema dos Santos, Cristina Maria; Rufino Mendonça, Rosângela; Vieira do Carmo, Maria Auxiliadora; Astofi-Filho, Spartaco
Focal epithelial hyperplasia (FEH) is a rare infection caused by human papillomavirus (HPV) types 13 or 32 believed to infect exclusively oral mucosa. This report illustrates a case of multiple conjunctival papillomas similar to oral FEH caused by HPV-13, consisting in the first description of its infection outside the oral mucosa in a healthy patient.
Torrente, Mariela C.; Rodrigo, Juan P.; Haigentz, Missak; Dikkers, Frederik G.; Rinaldo, Alessandra; Takes, Robert P.; Olofsson, Jan; Ferlito, Alfio
Although the association and clinical significance of human papillomavirus (HPV) infections with a subset of head and neck cancers, particularly for oropharyngeal carcinoma, has recently been well documented, the involvement of HPV in laryngeal cancer has been inadequately evaluated. Herein we
Goodrum, Felicia; Caviness, Katie; Zagallo, Patricia
Viral persistence is the rule following infection with all herpesviruses. The β-herpesvirus, human cytomegalovirus (HCMV), persists through chronic and latent states of infection. Both of these states of infection contribute to HCMV persistence and to the high HCMV seroprevalence worldwide. The chronic infection is poorly defined molecularly, but clinically manifests as low-level virus shedding over extended periods of time and often in the absence of symptoms. Latency requires long-term maintenance of viral genomes in a reversibly quiescent state in the immunocompetent host. In this review, we focus on recent advances in the biology of HCMV persistence, particularly with respect to the latent mode of persistence. Latently infected individuals harbour HCMV genomes in haematopoietic cells and maintain large subsets of HCMV-specific T-cells. In the last few years, impressive advances have been made in understanding virus-host interactions important to HCMV infection, many of which will profoundly impact HCMV persistence. We discuss these advances and their known or potential impact on viral latency. As herpesviruses are met with similar challenges in achieving latency and often employ conserved strategies to persist, we discuss current and future directions of HCMV persistence in the context of the greater body of knowledge regarding α- and γ-herpesviruses persistence. © 2012 Blackwell Publishing Ltd.
Gheit, Tarik; Cornet, Iris; Clifford, Gary M
Little is known about factors determining HPV16 persistence and progression, but several studies have suggested that genetic variants may play a role.......Little is known about factors determining HPV16 persistence and progression, but several studies have suggested that genetic variants may play a role....
Anna Rosa Garbuglia
Full Text Available Human papillomavirus (HPV is currently considered to be a major etiologic factor, in addition to tobacco and alcohol, for oropharyngeal cancer (OPC development. HPV positive OPCs are epidemiologically distinct from HPV negative ones, and are characterized by younger age at onset, male predominance, and strong association with sexual behaviors. HPV16 is the most prevalent types in oral cavity cancer (OCC, moreover the prevalence of beta, and gamma HPV types is higher than that of alpha HPV in oral cavity.
Buck, Christopher B; Day, Patricia M; Thompson, Cynthia D; Lubkowski, Jacek; Lu, Wuyuan; Lowy, Douglas R; Schiller, John T
Sexually transmitted human papillomaviruses (HPVs) are the primary cause of cervical cancer. Recent advances in techniques for production of papillomaviral vectors [known as pseudoviruses (PsVs)] have made it possible to perform high-throughput screens for compounds that might block the initial stages of papillomavirus infection. We have used PsVs to screen a variety of compounds that might function as inhibitors of HPV infection, with emphasis on human peptides previously implicated in innate antimicrobial immunity. Little is known about the possible activity of these peptides against nonenveloped viruses, such as HPVs. Our screen revealed that human alpha-defensins 1-3 [known as human neutrophil peptides (HNPs) 1-3] and human alpha-defensin 5 (HD-5) are potent antagonists of infection by both cutaneous and mucosal papillomavirus types. In contrast, human beta-defensins 1 and 2 displayed little or no anti-HPV activity. HD-5 was particularly active against sexually transmitted HPV types, with 50% inhibitory doses in the high ng/ml range. Microscopic studies of PsV inhibition by the alpha-defensins revealed that they block virion escape from endocytic vesicles but not virion binding or internalization. Consistent with this finding, PsVs remained susceptible to inhibition by alpha-defensins for many hours after initial binding to cells. HNPs 1-3 and HD-5 have been reported to be present in the female genital tract at levels that overlap those that inhibit HPVs in vitro, suggesting that they could present a natural barrier to the sexual transmission of HPV and could serve as the basis of a broad-spectrum topical microbicide.
Full Text Available Cervical cancer is one of the most common cancers in women worldwide, particularly in developing countries. The viral origin of cervical cancer has been proven beyond any reasonable doubt. Persistent infection with certain subsets of human papillomaviruses is recognized as a necessary cause for the development of cervical cancer. Persistence of oncogenic HPVs, immunodeficiency, high HPV viral load and cofactors like smoking, multiple sex partners and poor nutrition predispose to cervical cancer. Prophylactic vaccines using HPV virus-like particles containing capsid protein L1 have shown protection against disease in animals and are currently undergoing clinical trials. Therapeutic vaccines using HPV E6 and E7 proteins are also being investigated for their ability to remove residual infection.
Objectives: The current descriptive study aimed to determine university students' knowledge and attitudes regarding cervical cancer, human papillomavirus (HPV), and HPV vaccines in Turkey. Participants: A total of 800 students participated. Methods: This study was carried out between September 1, 2012, and October 30, 2012, in 8 female…
Marel, J. van der
Cervical cancer is the fourth most common cancer in women, with more than half a million new cases worldwide each year. In the majority of cervical cancers a persistent infection with high-risk (hr) Human papillomavirus (HPV) types has been proven to be the causative agent. Prevention of cervical
Schmeink, C.E.; Massuger, L.F.A.G.; Lenselink, C.H.; Quint, W.G.V.; Melchers, W.J.G.; Bekkers, R.L.M.
OBJECTIVE: To estimate the effect of the menstrual cycle and oral contraceptive pill (OCP) use on the prevalence, incidence, and persistence of human papillomavirus (HPV). METHODS: A longitudinal study was conducted among 2,065 women aged 18-29 years. The women returned a self-collected
Stern, Peter L; van der Burg, Sjoerd H; Hampson, Ian N; Broker, Thomas R; Fiander, Alison; Lacey, Charles J; Kitchener, Henry C; Einstein, Mark H
This chapter reviews the current treatment of chronic and neoplastic human papillomavirus (HPV)-associated conditions and the development of novel therapeutic approaches. Surgical excision of HPV-associated lower genital tract neoplasia is very successful but largely depends on secondary prevention programmes for identification of disease. Only high-risk HPV-driven chronic, pre-neoplastic lesions and some very early cancers cannot be successfully treated by surgical procedures alone. Chemoradiation therapy of cervical cancer contributes to the 66-79% cervical cancer survival at 5 years. Outlook for those patients with persistent or recurrent cervical cancer following treatment is very poor. Topical agents such as imiquimod (immune response modifier), cidofovir (inhibition of viral replication; induction apoptosis) or photodynamic therapy (direct damage of tumour and augmentation of anti-tumour immunity) have all shown some useful efficacy (~50-60%) in treatment of high grade vulvar intraepithelial neoplasia (VIN). Provider administered treatments of genital warts include cryotherapy, trichloracetic acid, or surgical removal which has the highest primary clearance rate. Patient applied therapies include podophyllotoxin and imiquimod. Recurrence after "successful" treatment is 30-40%. Further improvements could derive from a rational combination of current therapy with new drugs targeting molecular pathways mediated by HPV in cancer. Small molecule inhibitors targeting the DNA binding activities of HPV E1/E2 or the anti-apoptotic consequences of E6/E7 oncogenes are in preclinical development. Proteasome and histone deacetylase inhibitors, which can enhance apoptosis in HPV positive tumour cells, are being tested in early clinical trials. Chronic high-risk HPV infection/neoplasia is characterised by systemic and/or local immune suppressive regulatory or escape factors. Recently two E6/E7 vaccines have shown some clinical efficacy in high grade VIN patients and this
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.
Westrich, Joseph A; Warren, Cody J; Pyeon, Dohun
A majority of human papillomavirus (HPV) infections are asymptomatic and self-resolving in the absence of medical interventions. Various innate and adaptive immune responses, as well as physical barriers, have been implicated in controlling early HPV infections. However, if HPV overcomes these host immune defenses and establishes persistence in basal keratinocytes, it becomes very difficult for the host to eliminate the infection. The HPV oncoproteins E5, E6, and E7 are important in regulating host immune responses. These oncoproteins dysregulate gene expression, protein-protein interactions, posttranslational modifications, and cellular trafficking of critical host immune modulators. In addition to the HPV oncoproteins, sequence variation and dinucleotide depletion in papillomavirus genomes has been suggested as an alternative strategy for evasion of host immune defenses. Since anti-HPV host immune responses are also considered to be important for antitumor immunity, immune dysregulation by HPV during virus persistence may contribute to immune suppression essential for HPV-associated cancer progression. Here, we discuss cellular pathways dysregulated by HPV that allow the virus to evade various host immune defenses. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
Dornbusch, Hans Jürgen; Stiris, Tom; Del Torso, Stefano; Ross-Russell, Robert; Zavrsnik, Jernej; Wettergren, Björn; Mercier, Jean-Christophe; Valiulis, Arunas; Hadjipanayis, Adamos
The European Academy of Paediatrics (EAP) is gravely concerned about the human papillomavirus (HPV) vaccination crisis in Japan and particularly about the negative position taken by governmental authorities. Given that the HPV vaccine is both safe and effective, there is no recognizable reason to date to withhold this lifesaving and cost effective public health measure from a population. Therefore, the EAP strongly encourages the Japanese health authorities to actively support HPV vaccination for the future health of their children and adolescents. © 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).
Chin-Hong, Peter V
Human papillomavirus (HPV) is a common infection in kidney transplant recipients. HPV causes cervical, anal, vulvar, vaginal, penile and head and neck cancers. Kidney transplant recipients have a disproportionate burden of disease given prolonged immunosuppression. Given the long pre-invasive state of precancer lesions such as cervical intraepithelial neoplasia (CIN) and anal intraepithelial neoplasia (AIN) most HPV-cancers are preventable with screening and targeted treatment of disease. Pre-transplant vaccination of age-eligible kidney transplant recipients is otherwise ideal. Copyright © 2016 Elsevier Inc. All rights reserved.
Wentzensen, Nicolas; Wacholder, Sholom; Kinney, Walter; Gage, Julia C.; Castle, Philip E.
Strong evidence now supports the adoption of cervical cancer prevention strategies that explicitly focus on persistent infection with the causal agent, human papillomavirus (HPV). To inform an evidence-based transition to a new public health approach for cervical cancer screening, we summarize the natural history and cervical carcinogenicity of HPV and discuss the promise and uncertainties of currently available screening methods. New HPV infections acquired at any age are virtually always benign, but persistent infections with one of approximately 12 carcinogenic HPV types explain virtually all cases of cervical cancer. In the absence of an overtly persistent HPV infection, the risk of cervical cancer is extremely low. Thus, HPV test results predict the risk of cervical cancer and its precursors (cervical intraepithelial neoplasia grade 3) better and longer than cytological or colposcopic abnormalities, which are signs of HPV infection. The logical and inevitable move to HPV-based cervical cancer prevention strategies will require longer screening intervals that will disrupt current gynecologic and cytology laboratory practices built on frequent screening. A major challenge will be implementing programs that do not overtreat HPV-positive women who do not have obvious long-term persistence of HPV or treatable lesions at the time of initial evaluation. The greatest potential for reduction in cervical cancer rates from HPV screening is in low-resource regions that can implement infrequent rounds of low-cost HPV testing and treatment. PMID:21282563
Alberts, Catharina Johanna; Schim van der Loeff, Maarten F.; Papenfuss, Mary R.; da Silva, Roberto José Carvalho; Villa, Luisa Lina; Lazcano-Ponce, Eduardo; Nyitray, Alan G.; Giuliano, Anna R.
Background: Studies in women indicate that some sexually transmitted infections promote human papillomavirus (HPV) persistence and carcinogenesis. Little is known about this association in men; therefore, we assessed whether Chlamydia trachomatis (CT) infection and herpes simplex virus type 2
Deriemaeker, Hanne; Michielsen, Dirk; Reichman, Gina; Devroey, Dirk; Cammu, Hendrik
Introduction The aim of this study was to examine the knowledge of Belgian university students about the human papillomavirus (HPV) and HPV?vaccination. Material and methods During a period of two months we administered an online questionnaire, which contained 29 questions, to 3332 students of the Free University of Brussels. Of the 433 completed questionnaires, 346 were included by age (18?30 years) and completeness of responded questionnaires. These formed the study group. Results Of the 34...
Reeves, W C; Arosemena, J R; Garcia, M; de Lao, S L; Cuevas, M; Quiroz, E; Caussy, D; Rawls, W E
Little is known of the natural history of genital human papillomavirus (HPV) infections in women from high-risk populations. Samples were collected from 183 Panama City prostitutes and assessed for HPV (filter in situ DNA hybridization) and for sexually transmitted agents. The cohort was followed for 8 mo; 51% of subjects completed four monthly return visits and 16% were sampled eight times. The proportion of women found infected with HPV increased significantly with increasing numbers of consecutive samples tested; 38 (21%) of 183 women were positive after one visit and 46 (82%) of 56 who completed six visits were infected. The pattern of viral detection over time was not random, which implied that most prostitutes were persistently infected with genital HPVs and that either scattered foci of infection or periodic reactivation of latent virus occurred. Our findings suggest that multiple sampling is necessary to accurately estimate HPV infection rates and to define whether patterns of DNA expression are present.
Muñoz-Santos, C; Pigem, R; Alsina, M
Human papillomavirus infection is very common. In this article, we review the latest developments in the treatment of lesions caused by this virus, with a particular focus on anogenital warts. Sinecatechins and new imiquimod formulations are among the most significant new developments. Others include photodynamic therapy and intralesional immunotherapy, but there is insufficient evidence to recommend their routine use. Finally, while therapeutic vaccines and inhibitory molecules appear to hold great promise, they are still in the early phases of investigation. More studies are needed, and these should have similar designs, larger samples, and sufficiently long follow-up periods to enable the direct comparison of the short-term and long-term effectiveness of different treatment options. Copyright © 2012 Elsevier España, S.L. and AEDV. All rights reserved.
Nuovo, G.J. (Columbia Presbyterian Medical Center, New York, NY (USA)); Pedemonte, B.M. (Harlem Hospital Medical Center, New York, NY (USA))
The authors analyzed cervical intraepithelial neoplasias (CINs) detected after cryotherapy to determine if recurrence is associated with the same human papillomavirus (HPV) type found in the original lesion. Eight women had detectable HPV DNA in CINs that occurred after ablation of another CIN, and for each patient the HPV type in the pretreatment lesion was different from that in the CIN that appeared after cryotherapy. This compares with 12 women who had HPV detected in two or more CINs present at the same time, 11 of whom had the same HPv type noted. they concluded that although multiple, simultaneous CINs in a woman often contain the same HPV type, recurrent CINs that occur after cryotherapy contain an HPV type different from that present in the pretreatment lesion.
For many years it has been thought that a significant proportion of cervical cancer could be attributed to sexually transmitted agents, such as sperm, smegma, Treponema pallidum, Gonococcus and herpes simplexvirus type 2. Recent advances of molecular biology, however, have revealed that human papillomavirus (HPV) might be the most causative virus of the disease. Since HPV type 16 DNA was found in a patient with cervical cancer in 1983, many HPV types have been cloned from cervical cancers, also from premalignant lesions (intraepithelial neoplasias). In Japan, we have found 6 new types of HPV (HPV 58, 59, 61, 62, 64, 67) in the female genital tract so far. Especially, HPV 58, which was cloned from a patient with cervical squamous cell carcinoma and was already fully sequenced, is thought to be an important agent for the development of cervical cancer as well as HPV 16. Now we are investigating extensively to clarify the real relationship between genital HPV infection and cervical cancer.
Kadish, Anna S; Einstein, Mark H
To review novel immunologic strategies for the prevention and treatment of human papillomavirus infection and associated diseases. Both animal model systems and human protocols are discussed. Many vaccine platforms for both prevention of human papillomavirus infection and treatment of associated disease have been developed. Virus-like particle constructs containing human papillomavirus capsid proteins have been shown to protect against human papillomavirus infection. Novel peptide or protein constructs containing modified E6 or E7 proteins, novel adjuvants, fusion proteins such as immunoglobulin-G-heavy chain E7, or heat shock proteins have been made as therapeutic modalities. In addition, many new recombinant vaccine vectors such as vaccinia, Listeria species, adenovirus, Semliki Forest vectors, and others have been developed as carriers of immunotherapeutic agents. Recently, chimeric virus-like particle vaccines have been developed to treat existing human papillomavirus-induced neoplasms. Immunotherapy protocols using a variety of recombinant vectors and modified human papillomavirus proteins induce in-vitro T cell responses and may lead to tumor regression. Vaccine-induced in-vitro immune reactivity and clinical vaccine effects are often not well associated. Further analysis of ongoing human immunotherapy trials is awaited.
Schiller, John T; Müller, Martin
The two licensed bivalent and quadrivalent human papillomavirus (HPV) L1 (the major papillomavirus virion protein) virus-like particle (VLP) vaccines are regarded as safe, effective, and well established prophylactic vaccines. However, they have some inherent limitations, including a fairly high production and delivery cost, virus-type restricted protection, and no reported therapeutic activity, which might be addressed with the development of alternative dosing schedules and vaccine products. A change from a three-dose to a two-dose protocol for the licensed HPV vaccines, especially in younger adolescents (aged 9-13 years), is underway in several countries and is likely to become the future norm. Preliminary evidence suggests that recipients of HPV vaccines might derive prophylactic benefits from one dose of the bivalent vaccine. Substantial interest exists in both the academic and industrial sectors in the development of second-generation L1 VLP vaccines in terms of cost reduction-eg, by production in Escherichia coli or alternative types of yeast. However, Merck's nonavalent vaccine, produced via the Saccharomyces cerevisiae production system that is also used for their quadrivalent vaccine, is the first second-generation HPV VLP vaccine to be available on the market. By contrast, other pharmaceutical companies are developing microbial vectors that deliver L1 genes. These two approaches would add an HPV component to existing live attenuated vaccines for measles and typhoid fever. Prophylactic vaccines that are based on induction of broadly cross-neutralising antibodies to L2, the minor HPV capsid protein, are also being developed both as simple monomeric fusion proteins and as virus-like display vaccines. The strong interest in developing the next generation of vaccines, particularly by manufacturers in middle-to-high income countries, increases the likelihood that vaccine production will become decentralised with the hope that effective HPV vaccines will be
Chan, P J; Su, B C; Kalugdan, T; Seraj, I M; Tredway, D R; King, A
The present study demonstrated the presence of HPV gene sequences in Percoll-washed sperm cells using polymerase chain reaction primers targeting smaller gene regions. Up to 64% of the sperm specimens were shown to contain gene sequences indicative of the presence of HPV. Human papillomavirus type 16 was detected about twice as often as HPV type 18. The results suggest the possible role of sperm as a vector for HPV.
Santos-López, Gerardo; Márquez-Domínguez, Luis; Reyes-Leyva, Julio; Vallejo-Ruiz, Verónica
Human papillomavirus (HPV) refers to a group of viruses which belongs to a larger group, commonly referred to as papillomaviruses. These viruses are taxonomically located in the Papillomaviridae family. Papillomaviruses are small, non-enveloped with a genome of double-stranded DNA and they have affinity for epithelial tissue. Many of them are associated with human infection; they induce benign lesions of the skin (warts) and mucous membranes (condylomas), but they are also associated with some epithelial malignancies, such as cervical cancer and other tumors of the urogenital tract. Papillomaviridae contains 16 genera, which are named with a Greek letter prefix and the termination papillomavirus, e.g., Alphapapillomavirus, Betapapillomavirus, etcetera. From the clinical point of view, human papillomaviruses infecting the genital tract (which are located in the genus Alphapapilomavirus) have been divided into two groups: those of low risk, associated with benign genital warts, and those of high risk, with oncogenic potential, which are the etiological agents of cervical cancer. In this paper we review some relevant aspects of the structure, replication cycle and classification of human papillomaviruses.
Sánchez-Torices, María Soledad; Corrales-Millan, Rocío; Hijona-Elosegui, Jesús J
Human papillomavirus (HPV) infection is the most common human sexually transmitted disease. It is clinically relevant because this condition is necessary for the development of epithelial cervical cancer, and it is also a factor closely associated with the occurrence of diverse tumours and various benign and malignant lesions of the head and neck area. The infective mechanism in most of these cases is associated with sexual intercourse, but there is recent scientific evidence suggesting that HPV infection may also be acquired by other routes of infection not necessarily linked to sexual contact. One of them is vertical transmission from mother to child, either during pregnancy or at the time of delivery. The aim of our research was to study maternal-foetal HPV transmission during childbirth in detail, establishing the rate of oropharyngeal neonatal HPV in vaginal deliveries. The presence and type of HPV viral DNA at the time of delivery in samples of maternal cervical secretions, amniotic fluid, venous cord blood samples and neonatal oropharynx in pregnant women (and their babies) were determined. The rate of oropharyngeal neonatal HPV colonization in vaginal deliveries was 58.24%. The maternal and neonatal HPV colonization mechanism is essentially, but not exclusively, transvaginal. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.
Bosch, F X; Moreno, D; Redondo, E; Torné, A
Human papillomavirus (HPV) is the causative agent of 5% of human cancers. HPV infection is necessary for the development of cervical cancer and is responsible of a variable percentage of cancers of anus, vulva, vagina, penis, and oropharynx. Since 2007, 2 vaccines against HPV have been commercially available in Spain: bivalent (HPV types 16/18), and tetravalent (HPV types 6/11/16/18). In order to extend the protection afforded by HPV vaccines, a clinical program was launched in 2006 for the new nonavalent vaccine, including 9 HPV types (6/11/16/18/31/33/45/52/58). These types are responsible for 90% of cervical cancers, 82% of high-grade ano-genital pre-cancerous lesions, and 90% of genital warts. The purpose of this publication is to provide healthcare professionals with the scientific evidence that supports the new vaccine, as well as the clinical value that it offers in our environment. Copyright © 2017 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.
Traore, I M A; Zohoncon, T M; Ndo, O; Djigma, F W; Obiri-Yeboah, D; Compaore, T R; Guigma, S P; Yonli, A T; Traore, G; Ouedraogo, P; Ouedraogo, C M R; Traore, Y; Simpore, J
Cervical cancer usually occurs several years after persistent infection with oncogenic or high-risk human papillomavirus. The objective of this study was to determine carriage of 14 genotypes of high-risk human papillomavirus among women at Orodara and then characterize the genotypes found in these women. From June to July 2015, 120 women from the general population were recruited in the health district of Orodara. They voluntarily agreed to participate in the study. Endocervical samples were taken from these women prior to screening for precancerous lesions by visual inspection with acetic acid and lugol's iodine. Identification of high-risk human papillomavirus genotype was done using real-time PCR. High-risk human papillomavirus prevalence was 38.3% and the most common genotypes were HPV 52 (25.4%), HPV 33 (20.6%) and HPV 59 (11.1%). The HPV 66 was also identified with a prevalence of 9.5%. The HPV 16 and HPV 18 which are frequently associated with cancer worldwide were not found among the most frequent oncogenic HPV in women in Orodara.
Tummers, Bart; Van Der Burg, Sjoerd H.
Persistent infections with a high-risk type human papillomavirus (hrHPV) can progress to cancer. High-risk HPVs infect keratinocytes (KCs) and successfully suppress host immunity for up to two years despite the fact that KCs are well equipped to detect and initiate immune responses to invading pathogens. Viral persistence is achieved by active interference with KCs innate and adaptive immune mechanisms. To this end hrHPV utilizes proteins encoded by its viral genome, as well as exploits cellular proteins to interfere with signaling of innate and adaptive immune pathways. This results in impairment of interferon and pro-inflammatory cytokine production and subsequent immune cell attraction, as well as resistance to incoming signals from the immune system. Furthermore, hrHPV avoids the killing of infected cells by interfering with antigen presentation to antigen-specific cytotoxic T lymphocytes. Thus, hrHPV has evolved multiple mechanisms to avoid detection and clearance by both the innate and adaptive immune system, the molecular mechanisms of which will be dealt with in detail in this review. PMID:26008697
Full Text Available Persistent infections with a high-risk type human papillomavirus (hrHPV can progress to cancer. High-risk HPVs infect keratinocytes (KCs and successfully suppress host immunity for up to two years despite the fact that KCs are well equipped to detect and initiate immune responses to invading pathogens. Viral persistence is achieved by active interference with KCs innate and adaptive immune mechanisms. To this end hrHPV utilizes proteins encoded by its viral genome, as well as exploits cellular proteins to interfere with signaling of innate and adaptive immune pathways. This results in impairment of interferon and pro-inflammatory cytokine production and subsequent immune cell attraction, as well as resistance to incoming signals from the immune system. Furthermore, hrHPV avoids the killing of infected cells by interfering with antigen presentation to antigen-specific cytotoxic T lymphocytes. Thus, hrHPV has evolved multiple mechanisms to avoid detection and clearance by both the innate and adaptive immune system, the molecular mechanisms of which will be dealt with in detail in this review.
Tummers, Bart; Burg, Sjoerd H Van Der
Persistent infections with a high-risk type human papillomavirus (hrHPV) can progress to cancer. High-risk HPVs infect keratinocytes (KCs) and successfully suppress host immunity for up to two years despite the fact that KCs are well equipped to detect and initiate immune responses to invading pathogens. Viral persistence is achieved by active interference with KCs innate and adaptive immune mechanisms. To this end hrHPV utilizes proteins encoded by its viral genome, as well as exploits cellular proteins to interfere with signaling of innate and adaptive immune pathways. This results in impairment of interferon and pro-inflammatory cytokine production and subsequent immune cell attraction, as well as resistance to incoming signals from the immune system. Furthermore, hrHPV avoids the killing of infected cells by interfering with antigen presentation to antigen-specific cytotoxic T lymphocytes. Thus, hrHPV has evolved multiple mechanisms to avoid detection and clearance by both the innate and adaptive immune system, the molecular mechanisms of which will be dealt with in detail in this review.
Ferris, Daron; Samakoses, Rudiwilai; Block, Stan L
BACKGROUND: We present a long-term safety, immunogenicity, and effectiveness study of a quadrivalent human papillomavirus (HPV4) vaccine. METHODS: Sexually naive boys and girls aged 9 to 15 years (N = 1781) were assigned (2:1) to receive HPV4 vaccine or saline placebo at day 1 and months 2 and 6....... At month 30, the placebo group (n = 482) received HPV4 vaccine following the same regimen and both cohorts were followed through month 96. Subjects ≥16 years were eligible for effectiveness evaluations. The primary objective was to evaluate the long-term anti-HPV6/11/16/18 serological levels. The secondary...... objective was to estimate vaccine effectiveness against HPV6/11/16/18-related persistent infection or disease. RESULTS: For each of the HPV4 vaccine types, vaccination-induced anti-HPV response persisted through month 96. Among 429 subjects who received HPV4 vaccine at a mean age of 12, none developed HPV6...
Brotherton, Julia M L; Gold, Mike S; Kemp, Andrew S; McIntyre, Peter B; Burgess, Margaret A; Campbell-Lloyd, Sue
In 2007, Australia implemented the National human papillomavirus (HPV) Vaccination Program, which provides quadrivalent HPV vaccine free to all women aged 12-26 years. Following notification of 7 presumptive cases of anaphylaxis in the state of New South Wales, Australia, we verified cases and compared the incidence of anaphylaxis following HPV vaccination to other vaccines in comparable settings. We contacted all patients with suspected anaphylaxis and obtained detailed histories from telephone interviews and a review of medical records. A multidisciplinary team determined whether each suspected case met the standardized Brighton definition. Some participants also received skin-prick allergy testing for common antigens and components of the HPV vaccine. Of 12 suspected cases, 8 were classified as anaphylaxis. Of these, 4 participants had negative skin-prick test results for intradermal Gardasil. From the 269 680 HPV vaccine doses administered in schools, 7 cases of anaphylaxis were identified, which represents an incidence rate of 2.6 per 100 000 doses (95% CI 1.0-5.3 per 100 000). In comparison, the rate of identified anaphylaxis was 0.1 per 100 000 doses (95% CI 0.003-0.7) for conjugated meningococcal C vaccination in a 2003 school-based program. Based on the number of confirmed cases, the estimated rate of anaphylaxis following quadrivalent HPV vaccine was significantly higher than identified in comparable school-based delivery of other vaccines. However, overall rates were very low and managed appropriately with no serious sequelae.
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.
Katoulis, A C; Liakou, A; Bozi, E; Theodorakis, M; Alevizou, A; Zafeiraki, A; Mistidou, M; Stavrianeas, N G
Erythema multiforme (EM) is an acute self-limited immune-mediated reaction manifested by target skin lesions with mucous membrane involvement. The most common causes are infections and drugs. Vaccinations have been reported as a triggering factor, and they may be a frequent cause of EM in childhood. A 19-year-old female developed several target lesions of the hands and feet 10 days after the second dose of human papillomavirus (HPV) vaccine. Clinico-histologically, a diagnosis of EM minor was made. Treatment with topical corticosteroids and oral antihistamines resulted in complete clearance of the rash. Four months later, she received the last booster dose of the vaccine. A few subtle lesions appeared and disappeared spontaneously after a few days. Gardasil is a non-infectious vaccine, developed for the prevention of cervical cancer, precancerous genital lesions and genital warts. It delivers the major capsid (L1) protein of HPV types 6, 11, 16 and 18. Mild local reactions are the main adverse events. The only serious events are very rare cases of anaphylaxis. In our patient, the temporal relationship between the development of EM and the vaccination suggests that the HPV vaccine probably was the causal agent. This is the first published case of EM following HPV vaccination. Copyright 2009 S. Karger AG, Basel.
Stillo, Michela; Carrillo Santisteve, Paloma; Lopalco, Pier Luigi
Introduction: Between 2006 and 2009, two different human papillomavirus virus (HPV) vaccines were licensed for use: a quadrivalent (qHPVv) and a bivalent (bHPVv) vaccine. Since 2008, HPV vaccination programmes have been implemented in the majority of the industrialized countries. Since 2013, HPV vaccination has been part of the national programs of 66 countries including almost all countries in North America and Western Europe. Despite all the efforts made by individual countries, coverage rates are lower than expected. Vaccine safety represents one of the main concerns associated with the lack of acceptance of HPV vaccination both in the European Union/European Economic Area and elsewhere. Areas covered: Safety data published on bivalent and quadrivalent HPV vaccines, both in pre-licensure and post-licensure phase, are reviewed. Expert opinion: Based on the latest scientific evidence, both HPV vaccines seem to be safe. Nevertheless, public concern and rumors about adverse events (AE) represent an important barrier to overcome in order to increase vaccine coverage. Passive surveillance of AEs is an important tool for detecting safety signals, but it should be complemented by activities aimed at assessing the real cause of all suspect AEs. Improved vaccine safety surveillance is the first step for effective communication based on scientific evidence. PMID:25689872
Khallouf, Hadeel; Grabowska, Agnieszka K.; Riemer, Angelika B.
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
SUMMARY High-risk human papillomaviruses (HPVs) cause essentially all cervical cancers, most anal and oropharyngeal cancers, and some vaginal, vulvar, and penile cancers. Improved understanding of the pathogenesis of infection and the availability of newer tests are changing the approach to screening and diagnosis. Molecular tests to detect DNA from the most common high-risk HPVs are FDA approved for use in conjunction with cytology in cervical cancer screening programs. More-specific tests that detect RNA from high-risk HPV types are now also available. The use of molecular tests as the primary screening tests is being adopted in some areas. Genotyping to identify HPV16 and -18 has a recommended role in triaging patients for colposcopy who are high-risk HPV positive but have normal cytology. There are currently no recommended screening methods for anal, vulvar, vaginal, penile, or oropharyngeal HPV infections. HPV testing has limited utility in patients at high risk for anal cancer, but p16 immunohistochemistry is recommended to clarify lesions in tissue biopsy specimens that show moderate dysplasia or precancer mimics. HPV testing is recommended for oropharyngeal squamous cell tumors as a prognostic indicator. Ongoing research will help to improve the content of future guidelines for screening and diagnostic testing. PMID:26912568
Malik, Tufail; Imran, Mudassar; Jayaraman, Raja
A two-sex, deterministic ordinary differential equations model for human papillomavirus (HPV) is constructed and analyzed for optimal control strategies in a vaccination program administering three types of vaccines in the female population: a bivalent vaccine that targets two HPV types and provides longer duration of protection and cross-protection against some non-target types, a quadrivalent vaccine which targets an additional two HPV types, and a nonavalent vaccine which targets nine HPV types (including those covered by the quadrivalent vaccine), but with lesser type-specific efficacy. Considering constant vaccination controls, the disease-free equilibrium and the effective reproduction number Rv for the autonomous model are computed in terms of the model parameters. Local-asymptotic stability of the disease-free equilibrium is established in terms of Rv. Uncertainty and Sensitivity analyses are carried out to study the influence of various important model parameters on the HPV infection prevalence. Assuming the HPV infection prevalence in the population under the constant control, optimal control theory is used to devise optimal vaccination strategies for the associated non-autonomous model when the vaccination rates are functions of time. The impact of these strategies on the number of infected individuals and the accumulated cost is assessed and compared with the constant control case. Switch times from one vaccine combination to a different combination including the nonavalent vaccine are assessed during an optimally designed HPV immunization program. Copyright © 2016 Elsevier Ltd. All rights reserved.
Schouten, C.S.; Graaf, P. de; Bloemena, E.; Witte, B.I.; Braakhuis, B.J.; Brakenhoff, R.H.; Leemans, C.R.; Castelijns, J.A.; Bree, R. de
BACKGROUND AND PURPOSE: Patients with human papillomavirus-positive oropharyngeal squamous cell carcinomas have a better survival rate than those with human papillomavirus-negative oropharyngeal squamous cell carcinomas. DWI characterizes biologically relevant tumor features, and the generated ADC
Julio Pérez-Andino; Buck, Christopher B.; Katharina Ribbeck
Human Papillomaviruses (HPVs) are a diverse group of viruses that infect the skin and mucosal tissues of humans. A high-risk subgroup of HPVs is associated with virtually all cases of cervical cancer -. High-risk HPVs are transmitted sexually; however, the exact mechanisms by which sexual contact promotes virus infection remain uncertain. To study this question we asked whether capsids of HPV type 16 (a high-risk HPV) specifically interact with sperm cells. We tested if purified HPV16 v...
Deriemaeker, Hanne; Michielsen, Dirk; Reichman, Gina; Devroey, Dirk; Cammu, Hendrik
The aim of this study was to examine the knowledge of Belgian university students about the human papillomavirus (HPV) and HPV-vaccination. During a period of two months we administered an online questionnaire, which contained 29 questions, to 3332 students of the Free University of Brussels. Of the 433 completed questionnaires, 346 were included by age (18-30 years) and completeness of responded questionnaires. These formed the study group. Of the 346 included questionnaires (76% female), 48% were completed by medical students. The majority (65%) knew that both genders could be infected with HPV. Ninety-five percent of all medical students were aware of the existence of HPV, while 92% knew of the possibility to be vaccinated against the virus. Ninety percent of them were aware of the causal relationship between HPV infection and cervical cancer. 46% of the medical students were aware that HPV can cause anogenital cancers, and only 28% knew that HPV-vaccination could protect them against genital warts. Sixty percent of all female students were fully vaccinated against HPV, without any difference between medical and non-medical students. A very small part of all students (3%) believed that vaccination against HPV could enhance a promiscuous lifestyle. Almost 80% of respondents were aware of the existence of the human papillomavirus, its morbid potential and the HPV-vaccination.
Guidry, J T; Scott, R S
The etiological role of human papillomavirus (HPV) in anogenital tract and head and neck cancers is well established. However, only a low percentage of HPV-positive women develop cancer, indicating that HPV is necessary but not sufficient in carcinogenesis. Several biological and environmental cofactors have been implicated in the development of HPV-associated carcinoma that include immune status, hormonal changes, parity, dietary habits, tobacco usage, and co-infection with other sexually transmissible agents. Such cofactors likely contribute to HPV persistent infection through diverse mechanisms related to immune control, efficiency of HPV infection, and influences on tumor initiation and progression. Conversely, HPV co-infection with other factors may also harbor anti-tumor effects. Here, we review epidemiological and experimental studies investigating human immunodeficiency virus (HIV), herpes simplex virus (HSV) 1 and 2, human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), BK virus (BKV), JC virus (JCV), and adeno-associated virus (AAV) as viral cofactors in or therapeutic factors against the development of genital and oral HPV-associated carcinomas. Copyright © 2016 Elsevier B.V. All rights reserved.
The beta genus comprises more than 50 beta human papillomavirus (HPV) types that are suspected to be involved, together with ultraviolet (UV) irradiation, in the development of non-melanoma skin cancer (NMSC), the most common form of human cancer. Two members of the genus beta, HPV5 and HPV8, were first identified in patients with a genetic disorder, epidermodysplasia verruciformis (EV), that confers high susceptibility to beta HPV infection and NMSC development. The fact that organ transplant recipients (OTRs) with an impaired immune system have an elevated risk of NMSC raised the hypothesis that beta HPV types may also be involved in skin carcinogenesis in non-EV patients. Epidemiological studies have shown that serological and viral DNA markers are weakly, but significantly, associated with history of NMSC in OTRs and the general population. Functional studies on mucosal high-risk (HR) HPV types have clearly demonstrated that the products of two early genes, E6 and E7, are the main viral oncoproteins, which are able to deregulate events closely linked to transformation, such as cell cycle progression and apoptosis. Studies on a small number of beta HPV types have shown that their E6 and E7 oncoproteins also have the ability to interfere with the regulation of key pathways/events associated with cellular transformation. However, the initial functional data indicate that the molecular mechanisms leading to cellular transformation are different from those of mucosal HR HPV types. Beta HPV types may act only at early stages of carcinogenesis, by potentiating the deleterious effects of other carcinogens, such as UV radiation. Copyright © 2016 Elsevier B.V. All rights reserved.
Meerding, Willem Jan; van Ballegooijen, Marjolein; Burger, Matthé P. M.; van den Akker-van Marle, M. Elske; Quint, Wim G. V.; Habbema, J. Dik F.
The objective of this article was to evaluate the utility of high-risk human papillomavirus (HR-HPV) testing for triage of women referred for colposcopy because of abnormal smears. We considered women with persistent mild or moderate dyskaryosis and women with severe dyskaryosis who were referred
F. Xavier Bosch
Full Text Available Cervical cancer has been recognized as a rare outcome of a common Sexually Transmitted Infection (STI. The etiologic association is restricted to a limited number of viral types of the family of the Human Papillomaviruses (HPVs. The association is causal in nature and under optimal testing systems, HPV DNA can be identified in all specimens of invasive cervical cancer. As a consequence, it has been claimed that HPV infection is a necessary cause of cervical cancer. The evidence is consistent worldwide and implies both the Squamous Cell Carcinomas (SCC, the adenocarcinomas and the vast majority (i.e. > 95% of the immediate precursors, namely High Grade Squamous Intraepithelial Lesions (HSIL/Cervical Intraepithelial Neoplasia 3 (CIN3/Carcinoma in situ. Co-factors that modify the risk among HPV DNA positive women include the use of oral contraceptives (OC for five or more years, smoking, high parity (five or more full term pregnancies and previous exposure to other sexually transmitted diseases such as Chlamydia Trachomatis (CT and Herpes Simplex Virus type 2 (HSV-2. Women exposed to the Human Immunodeficiency Virus (HIV are at high risk for HPV infection, HPV DNA persistency and progression of HPV lesions to cervical cancer.
Bruni, Laia; Serrano, Beatriz; Bosch, Xavier; Castellsagué, Xavier
Human papillomavirus (HPV) related disease remains a major cause of morbidity and mortality worldwide. Prophylactic vaccines have been recognized as the most effective intervention to control for HPV-related diseases. This article reviews the major phaseii/iii trials of the bivalent (HPVs16/18), quadrivalent (HPVs6/11/16/18), and the recently approved 9-valent vaccine (HPVs6/11/16/18/31/33/45/52/58). Large trials have been conducted showing the safety, immunogenicity and high efficacy of the bivalent and quadrivalent vaccines in the prevention of pre-invasive lesions and infection, especially when administered at young ages before exposure to HPV. Trials of the 9-valent vaccine have also demonstrated the safety, immunogenicity and efficacy of the vaccine in the prevention of infection and disease associated with the vaccine types, and its potential to substantially increase the overall prevention of HPV-related diseases. Post-licensure country reports have shown the recent and early impact of these vaccines at population level after the implementation of established HPV vaccination programs, including decreases in the prevalence of vaccine HPV types, the incidence of genital warts, and the incidence of high-grade cervical abnormalities. If widely implemented, current HPV vaccines may drastically reduce the incidence of cervical cancer and other HPV-related cancers and diseases. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Polek, Carolee; Hardie, Thomas
To explore the association between lesbians' knowledge of human papillomavirus (HPV) cancer risk with age, education, and openness with a woman's healthcare provider; and to explore the relationship between lesbians' knowledge of female-to-female HPV transmission with age, education, and openness with one's physician. A descriptive correlational survey. Surveys were distributed at lesbian and gay community events such as Bingo A-Go-Go; Rainbow Support Group meetings; Lesbian, Gay, and Bisexual Student Union of the University of Delaware meetings; and the Second Annual Women's Conference of the Women's Project of CAMP (Create a More Positive) Rehoboth. 96 women who self-identified as lesbian, bisexual, or transgender and lived in the state of Delaware. A 35-question survey, modified from an existing survey from the Delaware Breast Cancer Coalition and Centers for Disease Control and Prevention National Health Interview Survey. Knowledge of HPV transmission, age, education, openness about sexual preference with physician, sexual preference, and knowledge of the relationship between HPV and development of cancer. Twenty-nine women (30%) either did not know or did not believe that HPV could be spread by female-to-female sexual contact. Similarly, 29 (30%) of the women did not identify HPV as a cancer risk. Lack of HPV knowledge was prevalent in this population of women. Cultural awareness by nurses is essential when discussing cancer prevention and early detection for this vulnerable population. Every woman, regardless of sexual orientation, needs to be informed about routine health screenings, vaccinations, and relative risk for the development of diseases. Culturally competent interventions are essential and are a priority for health professionals who screen and educate women about their healthcare needs.
Sander, Bente Braad; Rebolj, Matejka; Valentiner-Branth, Palle
Cervical screening has helped decrease the incidence of cervical cancer, but the disease remains a burden for women. Human Papillomavirus (HPV) vaccination is now a promising tool for control of cervical cancer. Nordic countries (Denmark, Finland, Greenland, Iceland, Norway and Sweden) are relati......Cervical screening has helped decrease the incidence of cervical cancer, but the disease remains a burden for women. Human Papillomavirus (HPV) vaccination is now a promising tool for control of cervical cancer. Nordic countries (Denmark, Finland, Greenland, Iceland, Norway and Sweden...
malin and embedded in paraffin. light microscopy. Sections of rumour and the adjacent normal tissue were evaluated with special emphasis on epithelial changes consistent with HPV lesions.13. Inununocytochemistry. HPV structural proteins (group-specific papillomavirus capsid antigens) were demonstrared by means of ...
Ginori, Alessandro; Barone, Aurora; Santopietro, Rosa; Barbanti, Gabriele; Cecconi, Filippo; Tripodi, Sergio Antonio
Basaloid squamous cell carcinoma is a biologically aggressive neoplasm mainly found in the head and neck region. Recently, four cases of basaloid squamous cell carcinoma of the bladder have been reported, and three of them occurred in patients with neurogenic bladder, repeated catheterizations and human papillomavirus infection of the urinary tract. To the best of our knowledge, none of the patients affected by basaloid squamous cell carcinoma of the bladder described in the literature had documented genital involvement by human papillomavirus. Herein, we describe the case of a woman with neurogenic bladder affected by basaloid squamous cell carcinoma of the bladder and by a concomitant genital tract human papillomavirus infection. © 2014 The Japanese Urological Association.
Lai, Y M; Lee, J F; Huang, H Y; Soong, Y K; Yang, F P; Pao, C C
To investigate the presence of human papillomavirus (HPV) in human sperm cells and to evaluate potential effects of HPV on the sperm functions. A descriptive clinical study. Specimens of semen were collected from 24 randomly selected patients who attended the fertility clinics at Chang Gung Memorial Hospital. The presence of HPV DNA and RNA were examined by polymerase chain reaction. Semen quality and sperm cell function were analyzed by computer-aided autoanalyzer. Human papillomavirus type 16 DNA and RNA were found in 6 (25%) and 2 (8%) of the sperm cells specimens, respectively. Human papillomavirus type 18 DNA and RNA were present in 11 (46%) and 5 (21%) of the same sperm cells specimens, respectively. Incidence of asthenozoospermia among patients infected with either HPV was significantly higher than in those without HPV in their sperm cells (75% versus 8%). Although performance of curvilinear velocity, straight-line velocity, and mean amplitude of lateral head displacement was significantly lower in HPV-infected specimens, the differences of linearity, beat cross frequency, and straightness were not statistically significant. These results suggest that human papillomavirus can be found in human sperm cells and that certain HPV-specific genes are actively transcribed. Sperm motility parameters seem to be affected by the presence of HPV in the sperm cells, and also the incidence of asthenozoospermia may be associated with HPV infection.
Groves, Ian J; Coleman, Nicholas
Human papillomaviruses (HPVs) are a necessary cause of carcinoma of the cervix and other mucosal epithelia. Key events in high-risk HPV (HRHPV)-associated neoplastic progression include persistent infection, deregulated expression of virus early genes in basal epithelial cells and genomic instability causing secondary host genomic imbalances. There are multiple mechanisms by which deregulated virus early gene expression may be achieved. Integration of virus DNA into host chromosomes is observed in the majority of cervical squamous cell carcinomas (SCCs), although in ∼15% of cases the virus remains extrachromosomal (episomal). Interestingly, not all integration events provide a growth advantage to basal cervical epithelial cells or lead to increased levels of the virus oncogenes E6 and E7, when compared with episome-containing basal cells. The factors that provide a competitive advantage to some integrants, but not others, are complex and include virus and host contributions. Gene expression from integrated and episomal HRHPV is regulated through host epigenetic mechanisms affecting the virus long control region (LCR), which appear to be of functional importance. New approaches to treating HRHPV-associated mucosal neoplasia include knockout of integrated HRHPV DNA, depletion of virus transcripts and inhibition of virus early gene transcription through targeting or use of epigenetic modifiers. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Abreu André L P
Full Text Available Abstract Human Papillomavirus (HPV is the most common sexually transmitted virus. Worldwide, the most common high-risk (HR-HPV are -16/18, and approximately 70% of cervical cancers (CC are due to infection by these genotypes. Persistent infection by HR-HPV is a necessary but not sufficient cause of this cancer, which develops over a long period through precursor lesions, which can be detected by cytological screening. Although this screening has decreased the incidence of CC, HPV-related cervical disease, including premalignant and malignant lesions, continues to be a major burden on health-care systems. Although not completely elucidated, the HPV-driven molecular mechanisms underlying the development of cervical lesions have provided a number of potential biomarkers for both diagnostic and prognostic use in the clinical management of women with HPV-related cervical disease, and these biomarkers can also be used to increase the positive predictive value of current screening methods. In addition, they can provide insights into the biology of HPV-induced cancer and thus lead to the development of nonsurgical therapies. Considering the importance of detecting HPV and related biomarkers, a variety of methods are being developed for these purposes. This review summarizes current knowledge of detection methods for HPV, and related biomarkers that can be used to discriminate lesions with a high risk of progression to CC.
Reeves, W C; Brinton, L A; García, M; Brenes, M M; Herrero, R; Gaitán, E; Tenorio, F; de Britton, R C; Rawls, W E
To evaluate a possible association between infection with human papillomavirus (HPV) and cervical cancer, we performed a multicenter case-control study in Latin America of 759 cases of invasive cervical cancer and 1467 randomly selected age-matched controls. Demographic, sexual, behavioral, and other clinical data were obtained by interview, and HPV DNA was assayed in cervical-swab specimens with use of filter in situ hybridization. Cervical infection with HPV 16 or 18 or both was strongly associated with cervical cancer. HPV DNA was detected in 62 percent of the cases but only 32 percent of the controls, and the relative risk of cancer increased from 2.1 (95 percent confidence interval, 1.6 to 2.8) to 9.1 (6.1 to 13.6) with hybridization reactions of increasing strength. Although the number of sexual partners, age at first intercourse, number of live births, and Pap-smear history were also significant risk factors, the strong associations between infection with HPV 16 or 18 or both and cervical cancer persisted after we adjusted for these variables. These observations are consistent with the hypothesis that genital infection with HPV 16 or 18 may have a role in the pathogenesis of cervical cancer. Other well-known risk factors were also identified in the study, but they did not affect the association between HPV and cervical cancer.
Prue, G; Lawler, M; Baker, P; Warnakulasuriya, S
Human papillomavirus (HPV) contributes to the most common sexually transmitted infections, with repeated and persistent infection with particular types causing disease in both men and women. Infection with low-risk HPV types can lead to genital warts and benign lesions of the oral cavity, while high-risk types can cause various HPV-related malignancies. The incidence of head and neck cancers has been rising in the past number of decades mostly due to oropharyngeal cancer linked to HPV infection. HPV vaccination has been shown to be effective for cervical and other anogenital HPV-related cancers, and there is significant potential for HPV vaccination to prevent oropharyngeal cancers, given that the HPV types implicated in this disease can be protected against by the HPV vaccine. Few countries have implemented a universal HPV vaccination programme for males and females, with many countries arguing that female-only vaccination programmes protect males via herd immunity and that men who have sex with men will be protected via targeted vaccination programmes. We argue these may be limited in their effectiveness. We propose that the most effective, practical, ethical and potentially cost-effective solution is universal HPV vaccination that might lead to control of HPV-related diseases in men and women alike. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Qing, Song; Tulake, Wuniqiemu; Ru, Mingfang; Li, Xiaohong; Yuemaier, Reziwanguli; Lidifu, Dilare; Rouzibilali, Aierken; Hasimu, Axiangu; Yang, Yun; Rouziahong, Reziya; Upur, Halmurat; Abudula, Abulizi
It is known that high-risk human papillomavirus infection is the main etiological factor in cervical carcinogenesis. However, human papillomavirus screening is not sufficient for early diagnosis. In this study, we aimed to identify potential biomarkers common to cervical carcinoma and human papillomavirus infection by proteomics for human papillomavirus-based early diagnosis and prognosis. To this end, we collected 76 cases of fresh cervical tissues and 116 cases of paraffin-embedded tissue slices, diagnosed as cervical squamous cell carcinoma, cervical intraepithelial neoplasia II-III, or normal cervix from ethnic Uighur and Han women. Human papillomavirus infection by eight oncogenic human papillomavirus types was detected in tissue DNA samples using a quantitative polymerase chain reaction. The protein profile of cervical specimens from human papillomavirus 16-positive squamous cell carcinoma and human papillomavirus-negative normal controls was analyzed by proteomics and bioinformatics. The expression of candidate proteins was further determined by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. We identified 67 proteins that were differentially expressed in human papillomavirus 16-positive squamous cell carcinoma compared to normal cervix. The quantitative reverse transcriptase-polymerase chain reaction analysis verified the upregulation of ASAH1, PCBP2, DDX5, MCM5, TAGLN2, hnRNPA1, ENO1, TYPH, CYC, and MCM4 in squamous cell carcinoma compared to normal cervix ( p potentially associated with human papillomavirus infection. Further validation studies of the profile will contribute to establishing auxiliary diagnostic markers for human papillomavirus-based cancer prognosis.
Pimenoff, Ville N; de Oliveira, Cristina Mendes; Bravo, Ignacio G
Every human suffers through life a number of papillomaviruses (PVs) infections, most of them asymptomatic. A notable exception are persistent infections by Human papillomavirus 16 (HPV16), the most oncogenic infectious agent for humans and responsible for most infection-driven anogenital cancers. Oncogenic potential is not homogeneous among HPV16 lineages, and genetic variation within HPV16 exhibits some geographic structure. However, an in-depth analysis of the HPV16 evolutionary history was still wanting. We have analyzed extant HPV16 diversity and compared the evolutionary and phylogeographical patterns of humans and of HPV16. We show that codivergence with modern humans explains at most 30% of the present viral geographical distribution. The most explanatory scenario suggests that ancestral HPV16 already infected ancestral human populations and that viral lineages co-diverged with the hosts in parallel with the split between archaic Neanderthal-Denisovans and ancestral modern human populations, generating the ancestral HPV16A and HPV16BCD viral lineages, respectively. We propose that after out-of-Africa migration of modern human ancestors, sexual transmission between human populations introduced HPV16A into modern human ancestor populations. We hypothesize that differential coevolution of HPV16 lineages with different but closely related ancestral human populations and subsequent host-switch events in parallel with introgression of archaic alleles into the genomes of modern human ancestors may be largely responsible for the present-day differential prevalence and association with cancers for HPV16 variants. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
Bollerup, Signe; Baldur-Felskov, Birgitte; Dehlendorff, Christian
BACKGROUND: The quadrivalent human papillomavirus vaccine was licensed in Denmark in 2006. Unlike women, men are not offered human papillomavirus vaccination free of charge but can have it at their own expense. We investigated human papillomavirus vaccine uptake by men in Denmark...... and the socioeconomic factors that may predict human papillomavirus vaccination. METHODS: Using the Civil Registration System, we identified all boys and men aged 9-26 years in 2006-2013 and their mothers. By linkage to Statistics Denmark and the National Prescription Registry, we obtained information on socioeconomic...... variables and human papillomavirus vaccination during the study period. Using Cox regression, we examined the associations between socioeconomic variables and human papillomavirus vaccination. RESULTS: Between 2006 and 2013, 6253 (0.8%) males aged 9-26 years were vaccinated against human papillomavirus...
Zhao, Xiaojun; Zhou, Zheng; Chen, Ye; Chen, Wen; Ma, Hongwei; Pu, Jinxian
Evidence is accumulating in estimating the potential role of human papillomavirus infection in prostate carcinogenesis. However, the results remain inconclusive. We measured the serostatus of antibodies to one of the high-risk human papillomaviruses, human papillomavirus 16, with a newly developed peptide microarray. Serum samples were collected from 75 untreated prostate cancer patients, along with 80 control subjects. We identified 12 peptides with significant differences in prostate cancer samples from all 241 peptides derived from human papillomavirus 16. Our results showed human papillomavirus 16 infection in 64.0% of prostate cancer serum samples, which is significantly different compared with the controls ( p human papillomavirus 16 infection and risk of prostate cancer. The different serostatus of antibodies in the two subgroups indicated that human papillomavirus 16 infection might occur and play a potential role of progression in a minority of prostate cancer.
18. Rabelo‑Santos SH, Zeferino L, Villa LL, Sobrinho JP,. Amaral RG, Magalhães AV. Human papillomavirus prevalence among women with cervical intraepithelial neoplasia III and invasive cervical cancer from Goiânia, Brazil. Mem Inst Oswaldo Cruz 2003;98:181‑4. 19. National Institute of Câncer José Alencar Gomes da.
Purpose: The purpose of this paper is to better understand what influences the intentions of college students to receive the human papillomavirus (HPV) vaccine. HPV is the most common sexually transmitted infection in the USA and cancers related to HPV are on the rise. Design/Methodology/Approach: A 2×2 experimental design was used to predict the…
This cross-sectional study describes the age-specific prevalence of human papillomavirus (HPV) infection and cytological abnormalities among this urban and peri-urban population. Method. Over the period March 2009 - September 2011, 1 524 women attending public sector primary healthcare clinics were invited to
Vermeulen, Christine Frederike Wilhelmine
Cervical cancer remains one of the leading causes of death from cancer among women worldwide. Organised screening programmes aim to trace precursor lesions in order to reduce cervical cancer incidence. Human papillomavirus (HPV) is a necessary cause for cervical carcinogenesis. Most HPV infections
Olesen, Tina Bech; Mwaiselage, Julius; Iftner, Thomas
The objective of the study was to assess risk factors for Human Papillomavirus (HPV) among men in Tanzania, both overall and in relation to HIV status. In a cross-sectional study conducted among 1,813 men in Tanzania, penile swabs were tested for HPV using Hybrid Capture 2 (HC2). Study participan...
Hauwers, K.W.M. d'
OBJECTIVES: To describe the type-specific prevalence of anal and cervical human papillomavirus (HPV) infections and the cytology in HIV-negative women without a history of cervical cancer, attending a colposcopy clinic. To examine if an HPV positive anal smear is related to anal pathology and
Baandrup, Louise; Thomsen, Louise T; Olesen, Tina Bech
The role of human papillomavirus (HPV) in colorectal cancer has been widely studied with conflicting results. We performed a systematic review and a meta-analysis to estimate the prevalence of HPV in colorectal adenocarcinomas and adenomas, and test the potential association....
Damm, Oliver; Horn, Johannes; Mikolajczyk, Rafael T; Kretzschmar, Mirjam E E|info:eu-repo/dai/nl/075187981; Kaufmann, Andreas M; Deleré, Yvonne; Ultsch, Bernhard; Wichmann, Ole; Krämer, Alexander; Greiner, Wolfgang
BACKGROUND: The aim of this study was to assess the cost-effectiveness of human papillomavirus (HPV) vaccination in addition to the current cervical cancer screening programme in Germany using a dynamic transmission model. METHODS: Based on a mathematical model simulating the transmission dynamics
Olesen, Tina Bech; Munk, Christian; Christensen, Jane
BACKGROUND: We performed a systematic review and meta-analysis to summarise the available data on the prevalence of human papillomavirus (HPV) among men in sub-Saharan Africa. METHODS: PubMed and Embase were searched up to 10 March 2014. Random effects meta-analyses were used to calculate a poole...
Low risk and high risk human papillomaviruses (HPVs) and cervical cancer in Zimbabwe: epidemiological evidence. M Chirara, G A Stanczuk, S A Tswana, L Nystrom, S Bergstrom, S R Moyo, M J Nzara. Abstract. No Abstract. Central African Journal of Medicine Vol. 47 (2) 2001: pp. 32-34.
South African Family Practice. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 55, No 5 (2013) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Human papillomavirus vaccine. J Souter. Abstract.
Cooper, Spring C.; Davies, Cristyn; McBride, Kate; Blades, Joanna; Stoney, Tanya; Marshall, Helen; Skinner, S. Rachel
Objective: Australia has implemented a nation-wide programme providing a human papillomavirus (HPV) vaccine to girls and boys through school-based programmes. Previous research has identified three distinct areas for attention: (1) lack of understanding about HPV and HPV vaccination, (2) young people's desire for involvement in decision-making…
Patel, Divya A.; Zochowski, Melissa; Peterman, Stephanie; Dempsey, Amanda F.; Ernst, Susan; Dalton, Vanessa K.
Objective: To examine human papillomavirus (HPV) vaccine intent and the effect of an educational intervention on vaccine uptake among female college students. Participants: Females aged 18 to 26 attending a university health service gynecology clinic (n = 256). Methods: Participants were randomized to receive either HPV-specific education with a…
Objective: To determine the prevalence of human papillomavirus (HPV) types in South African women with normal cervical cytology and to determine whether our results are comparable to what has been found elsewhere in the wortd. Design: Cervical smears were collected from 262 women. Setting: The Cape Town ...
Rusan, M; Klug, Tejs Ehlers; Henriksen, Jens-Jacob Mølby
The incidence of tonsillar carcinomas associated with Human Papillomavirus (HPV) infection has increased dramatically over the last three decades. In fact, currently in Scandinavia, HPV-associated cases account for over 80 % of tonsillar carcinoma cases. Yet, the epidemiology and natural history...
Background. Human papillomavirus (HPV) infection is well known to be associated with head and neck cancers (HNCs). HPV-associated HNCs are related to sexual behaviour, particularly the lifetime number of oral sex partners, but the epidemiology of oral and oropharyngeal HPV in South African men has not yet been ...
Bohr, Anne; Grønhøj, Christian; Lajer, Christel
The incidence of human papillomavirus (HPV)-associated oropharyngeal cancer is rising in the Western world, but little is known about transmission of the infection and the premalignant phase of the disease. In this article there is an overview of current knowledge with focus on transmission of HPV...
Rebolj, Matejka; Lynge, Elsebeth; Bonde, Jesper
Mass vaccination against human papillomavirus (HPV) genotypes 16 and 18 will, in the long term, reduce the incidence of cervical cancer, but screening will remain an important cancer control measure in both vaccinated and unvaccinated women. Since the 1960s, cytology screening has helped to reduce...
2 London School of Hygiene and Tropical Medicine, London, United Kingdom. Corresponding author: S Delany-Moretlwe (firstname.lastname@example.org). Human papillomavirus (HPV) is a common sexually transmitted infection (STI) affecting both men and women. HPV infections can be classified as either low- (LR) or high-risk ...
Hebnes, Julie Buchholt; Munk, Christian; Nøhr, Bugge
BACKGROUND: It is crucial to understand the epidemiology and natural history of human papillomavirus (HPV) infection in both men and women, to prevent the increasing HPV-related disease burden in men. Data on HPV prevalence among men in the general population are limited. In this cross...
Background. The national human papillomavirus (HPV) vaccination roll-out in South Africa provides two doses of Cervarix to all female Grade 4 learners in state schools. This study estimated the costs of vaccinating all learners in KwaZulu-Natal Province (females or males and females) using either the two- or three-dose ...
High prevalence of human papillomavirus 58 in Northeast Brazil. Annals of Medical and Health Sciences Research | Oct-Dec 2013 | Vol 3 | Issue 4 |. 505 of the cervical lesions of low‑grade to high‑grade and invasive cancer. Studies on the prevalence of genotypes indicate that. HPV 16 is the most prevalent type in the ...
Halmos, Gyorgy B; van der Laan, Tom P; van Hemel, Bettien M; Dikkers, Frederik G; Slagter-Menkema, Lorian; van der Laan, Bernard F A M; Schuuring, Ed
The purpose of this study was to detect human papillomavirus (HPV) infection in laryngeal neuroendocrine carcinoma (LNEC) and to explore the possible relationship between HPV-induced malignant transformation and prognosis in LNEC. Ten cases of LNEC from a tertiary referral hospital were
Introduction: Human papillomavirus (HPV) is one of the most common sexually transmitted infections and has been implicated in over 70% of cases of cervical cancer. This study assessed the knowledge of HPV infection and acceptability of HPV vaccination among nursing students in Benin City. Methodology: A ...
Cervical cancer is the most common female cancer in northern Nigeria, yet the pattern of infection with human papillomavirus, the principal aetiologic agent is unknown. This was a preliminary study conducted in two referral hospitals in order to establish base-line data on the prevalence and risk factors for the infection in ...
Brossfield, Jeralyn E.; Philip J. Chan; Patton, William C.; King, Alan
Purpose:Sperm cells have been shown to take up exogenous DNA readily. The hypothesis was that sperm washing would remove exogenous viral DNA infecting sperm cells. The objective was to compare three types of sperm washing procedures for their capacity to remove exogenous human papillomavirus (HPV) DNA from infected sperm.
Full Text Available We report here identification and validation of the first papillomavirus encoded microRNAs expressed in human cervical lesions and cell lines. We established small RNA libraries from ten human papillomavirus associated cervical lesions including cancer and two human papillomavirus harboring cell lines. These libraries were sequenced using SOLiD 4 technology. We used the sequencing data to predict putative viral microRNAs and discovered nine putative papillomavirus encoded microRNAs. Validation was performed for five candidates, four of which were successfully validated by qPCR from cervical tissue samples and cell lines: two were encoded by HPV 16, one by HPV 38 and one by HPV 68. The expression of HPV 16 microRNAs was further confirmed by in situ hybridization, and colocalization with p16INK4A was established. Prediction of cellular target genes of HPV 16 encoded microRNAs suggests that they may play a role in cell cycle, immune functions, cell adhesion and migration, development, and cancer. Two putative viral target sites for the two validated HPV 16 miRNAs were mapped to the E5 gene, one in the E1 gene, two in the L1 gene and one in the LCR region. This is the first report to show that papillomaviruses encode their own microRNA species. Importantly, microRNAs were found in libraries established from human cervical disease and carcinoma cell lines, and their expression was confirmed in additional tissue samples. To our knowledge, this is also the first paper to use in situ hybridization to show the expression of a viral microRNA in human tissue.
Ault, Kevin A; Joura, Elmar A; Kjaer, Susanne K
The primary objective of this report is to describe the detection of adenocarcinoma in situ (AIS) and associated human papillomavirus (HPV) type distribution that was observed in the context of two phase 3 clinical trials of a quadrivalent HPV6/11/16/18 vaccine. In this intention-to-treat analysis...
Suzana Orsini Machado de Sousa
Full Text Available Objective: The human papillomavirus is a group of DNA epitheliotrophic viruses associated with the etiology of benign and malignant oral warts. More than 100 types have been identified and among them, 24 have been found into the oral cavity. The aim of this study was to analyze human papillomavirus prevalence and its subtypes in 50 oral warts, of which 20 were squamous papillomas, 17 condylomaacuminatum and 13 verruca vulgaris. Method: In situ hybridization was used with biotinylated DNA probes for wide-spectrum HPV and with specific probes for human papillomavirus 6/11, human papillomavirus 16/18 and human papillomavirus 31/33. Results: Human papillomavirus was present in ten (20% of the 50 oral wart cases, 03 (3/20 squamous papillomas, 05 (5/17 condyloma acuminatum and 02 (2/13 verruca vulgaris. Of these, 8 (16% were positive to the HPV probe 6/11 being 5 condyloma acuminatum, 1 squamous papilloma and 2 verruca vulgaris. Three cases (6% demonstrated positivity to the human papillomavirus probe 16/18, with 2 being cases of condyloma and the other a case of squamous papilloma. Of the six positive cases to the human papillomavirus probe 31/33, (12% 4 were condyloma acuminatum and 2 squamous papillomas. Conclusion: The human papillomavirus expression (20% found in this study was low, but within the average found in the literature. Nonetheless, in addition to in situ hybridization, other methods may be necessary for confirming the presence of human papillomavirus.
Giraldo, Paulo; Gonçalves, Ana K S; Pereira, Silvio A S; Barros-Mazon, Silvia; Gondo, Mariza L; Witkin, Steven S
Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases worldwide. We determined the frequency of HPV in the oral cavity of women with and without genital HPV lesions. All patients were seen at the Department of Gynecology, Women's Health Center and the State University of Campinas, Sao Paulo, Brazil and submitted to a general physical and gynecological examination plus an evaluation of the oral cavity. Detailed histories investigated their sexual practices. HPV in the oral cavity was determined by polymerase chain reaction using consensus primers in 70 women presenting with histopathology-confirmed clinical HPV lesions in the genital region and 70 women negative by gynecological, colposcopic and cytological examination for clinical or subclinical HPV lesions. Oral HPV was detected in 29 (20.7%) of the subjects. Among the positive women, 26 (89.7%) were also positive for genital HPV as opposed to only 3 (2.7%) who were genital HPV-negative (p fellatio (22% versus 19%). Patients with HPV genital infection have a greater frequency of HPV in their oral mucosa.
Buonaguro Franco M
Full Text Available Abstract Virtually all cases of cervical cancer are caused by persistent infections with a restricted set of human papillomaviruses (HPV. Some HPV types, like HPV16 and HPV18, are clear and powerful carcinogens. However, the categorization of the most weakly carcinogenic HPV types is extremely challenging. The decisions are important for screening test and vaccine development. This article describes for open discussion an approach recently taken by a World Health Organization International Agency for Research on Cancer (IARC Monographs Working Group to re-assess the carcinogenicity of different HPV types.
Porter, Samuel S; Stepp, Wesley H; Stamos, James D; McBride, Alison A
The life cycle of human papillomaviruses (HPV) is tightly regulated by the differentiation state of mucosal and cutaneous keratinocytes. To counteract viral infection, constitutively expressed cellular factors, which are defined herein as restriction factors, directly mitigate viral gene expression and replication. In turn, some HPV gene products target these restriction factors and abrogate their anti-viral effects to establish efficient gene expression and replication programs. Ironically, in certain circumstances, this delicate counterbalance between viral gene products and restriction factors facilitates persistent infection by HPVs. This review serves to recapitulate the current knowledge of nuclear restriction factors that directly affect the HPV infectious cycle. Published by Elsevier B.V.
Schiffman, Mark; Clifford, Gary; Buonaguro, Franco M
Virtually all cases of cervical cancer are caused by persistent infections with a restricted set of human papillomaviruses (HPV). Some HPV types, like HPV16 and HPV18, are clear and powerful carcinogens. However, the categorization of the most weakly carcinogenic HPV types is extremely challenging. The decisions are important for screening test and vaccine development. This article describes for open discussion an approach recently taken by a World Health Organization International Agency for Research on Cancer (IARC) Monographs Working Group to re-assess the carcinogenicity of different HPV types. PMID:19486508
De, P; Budhwani, H
Transmission of the human papillomavirus (HPV) is a significant public health concern. HPV is preventable through a series of vaccinations; however, knowledge gaps exist as to which groups are least likely to initiate vaccination. Considering this gap, the aim of this study is to examine HPV vaccine initiation rates in racial minorities, comparing foreign-born individuals to their American-born peers. Population-based data from the 2013 National Health Interview Survey (NHIS), a repeated large-scale household interview survey of a statistically representative sample of the United States civilian non-institutionalized population, were applied. Data were derived from two survey modules: the family and summary adult modules. Sampling weights were employed to logistic regression modelling the outcome of HPV vaccine initiation. Foreign-born persons, African Americans, males, those lacking health insurance coverage and those without a medical home (usual place to receive care) held statistically lower rates of HPV vaccine initiation. Being college educated was associated with higher odds of HPV vaccine initiation. Our findings support the persistence of health disparities in racial minorities and foreign-born persons residing in the United States. Addressing these gaps will likely require both individual-level (e.g. targeted health education) and system-level (e.g. HPV vaccine promoting policies) interventions. Since health insurance coverage and having a medical home were significant associates of HPV vaccine initiation, attempts to coverage may improve HPV vaccine initiation rates. Additionally, policies which require HPV vaccination for school entry could boost coverage across all population groups, including boys, foreign-born persons and racial minorities. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.
Full Text Available Human papillomaviruses (HPVs are the etiological agents of several genital cancers, including cancer of the uterine cervix. The detection of HPV infection in genital samples may increase the sensitivity of primary and secondary screenings of cervical cancer. HPV testing may also improve the specificity of screening programs, resulting in the avoidance of overtreatment and cost savings for confirmatory procedures. The major determinants of clinical progression of HPV infection include persistence of HPV infection, involvement of high-risk HPV types, high HPV viral load, integration of viral DNA and presence of several potential cofactors. Signal amplification HPV-DNA detection techniques (Hybrid Capture II, Digene Corporation, USA are standardized, commercially available, and capable of detecting several high-risk HPV types. They also increase the sensitivity of screening for high-grade lesions in combination with cytology. The sensitivity of these techniques to detect high-grade lesions is higher than that of cytology, but the referral rate for colposcopy is greater. These techniques are approved for the triage to colposcopy of women with cervical smears interpreted as atypical squamous cells of undetermined significance. Triage and screening for cervical cancer using HPV will probably be restricted to women aged 30 years or older because of the high prevalence of infection in younger women. Amplification techniques are ideal for epidemiological studies because they minimize the misclassification of HPV infection status. These techniques can detect low HPV burden infections. Consensus primers amplify most genital types in one reaction, and the reverse hybridization of amplicons with type-specific probes allows for the typing of HPV-positive samples. Consensus PCR assays are currently under evaluation for diagnostic purposes. HPV testing is currently implemented for the clinical management of women.
Pérez-Andino, Julio; Buck, Christopher B; Ribbeck, Katharina
Human Papillomaviruses (HPVs) are a diverse group of viruses that infect the skin and mucosal tissues of humans. A high-risk subgroup of HPVs is associated with virtually all cases of cervical cancer -. High-risk HPVs are transmitted sexually; however, the exact mechanisms by which sexual contact promotes virus infection remain uncertain. To study this question we asked whether capsids of HPV type 16 (a high-risk HPV) specifically interact with sperm cells. We tested if purified HPV16 virions directly adsorb to live human sperm cells in native semen and in conditions that resemble the female genital tract. We found that HPV16 capsids bind efficiently to two distinct sites at the equatorial region of the sperm head surface. Moreover, we observed that the interaction of virus with sperm can be reduced by two HPV infection inhibitors, heparin and carrageenan. Our findings suggest that 1) sperm cells may serve as motile carriers that promote virus dispersal and mucosal penetration, and 2) blocking interactions between HPV16 and sperm cells may be an important strategy for the development of antiviral therapies.
Full Text Available Human Papillomaviruses (HPVs are a diverse group of viruses that infect the skin and mucosal tissues of humans. A high-risk subgroup of HPVs is associated with virtually all cases of cervical cancer -. High-risk HPVs are transmitted sexually; however, the exact mechanisms by which sexual contact promotes virus infection remain uncertain. To study this question we asked whether capsids of HPV type 16 (a high-risk HPV specifically interact with sperm cells. We tested if purified HPV16 virions directly adsorb to live human sperm cells in native semen and in conditions that resemble the female genital tract. We found that HPV16 capsids bind efficiently to two distinct sites at the equatorial region of the sperm head surface. Moreover, we observed that the interaction of virus with sperm can be reduced by two HPV infection inhibitors, heparin and carrageenan. Our findings suggest that 1 sperm cells may serve as motile carriers that promote virus dispersal and mucosal penetration, and 2 blocking interactions between HPV16 and sperm cells may be an important strategy for the development of antiviral therapies.
Thomsen, Louise T; Nygård, Mari; Stensen, Signe
Using a large, population-based survey, we assessed the levels and correlates of human papillomavirus (HPV) awareness among Scandinavian women after introduction of HPV vaccination. In 2011-2012, a random sample of women aged between 18 and 45 years from Denmark, Sweden and Norway received a ques......: OR=0.86, 95% CI: 0.80-0.92). HPV awareness in Scandinavia has increased since the introduction of HPV vaccination. However, 24-38% of Scandinavian women still have never heard of HPV. Future information efforts should target groups with low HPV awareness.......Using a large, population-based survey, we assessed the levels and correlates of human papillomavirus (HPV) awareness among Scandinavian women after introduction of HPV vaccination. In 2011-2012, a random sample of women aged between 18 and 45 years from Denmark, Sweden and Norway received...
Machado, Ana Paula; Gatto de Almeida, Flávia; Bonin, Camila Mareti; Martins Prata, Thiago Theodoro; Sobrinho Ávilla, Leandro; Junqueira Padovani, Cacilda Tezelli; Teixeira Ferreira, Alda Maria; dos Santos Fernandes, Carlos Eurico; Tozetti,Inês Aparecida
OBJECTIVES: The aim of this study was to identify highly oncogenic forms of human papillomavirus in the oral mucosa of asymptomatic men. METHODS: In this study, we analyzed samples of exfoliated cells from the oral cavity of 559 asymptomatic men. DNA-human papillomavirus was detected using the consensus primers PGMY09/11; viral genotyping was performed using type-specific PCR and restriction fragment length polymorphism. RESULTS: DNA-human papillomavirus was detected in 1.3% of the s...
sequences in adenovirus E1A and human papillomavirus. E7 proteins mediate interaction with the same set of cellular proteins; J. Virol. 66 6893–6902. Eckner R, Ludlow J W, Lill N L, Oldread E, Arany Z, Modjta- hedi N, DeCaprio J A, Livingston D M and Morgan J A 1996. Association of p300 and CBP with simian virus 40 ...
Kumar, Satish; Jena, Lingaraja; Daf, Sangeeta; Mohod, Kanchan; Goyal, Peyush; Varma, Ashok K.
Human papillomavirus (HPV) infection is the leading cause of cancer mortality among women worldwide. The molecular understanding of HPV proteins has significant connotation for understanding their intrusion in the host and designing novel protein vaccines and anti-viral agents, etc. Genomic, proteomic, structural, and disease-related information on HPV is available on the web; yet, with trivial annotations and more so, it is not well customized for data analysis, host-pathogen interaction, st...
Marlow, Laura A V; Wardle, Jane; Waller, Jo; Grant, Nina
Background With the introduction of human papillomavirus (HPV) testing and vaccination in the UK, health professionals will start to receive questions about the virus from their patients. This study aimed to identify the key questions about HPV that British women will ask when considering having an HPV test or vaccination. Methods Face-to-face interviews were carried out with 21 women to discover what they wanted to know about HPV. A thematic framework approach was used to analyse the data an...
Marlow, L. A. V.; Wardle, J.; Grant, N.; Waller, J.
Background With the introduction of human papillomavirus (HPV) testing and vaccination in the UK, health professionals will start to receive questions about the virus from their patients. This study aimed to identify the key questions about HPV that British women will ask when considering having an HPV test or vaccination.Methods Face-to-face interviews were carried out with 21 women to discover what they wanted to know about HPV. A thematic framework approach was used to analyse the data and...
Rebolj, Matejka; Pribac, Igor; Lynge, Elsebeth
Based on data from randomised controlled trials (RCT) on primary cervical screening, it has been reported that the problem of more frequent false-positive tests in Human Papillomavirus (HPV) DNA screening compared to cytology could be overcome. However, these reports predominantly operated with a...... with a narrow definition of a (false-)positive test. The aim of this paper was to illustrate how the narrow definition affected the measured adverse effects of HPV DNA screening compared with cytology screening....
Nigel Pereira; Kucharczyk, Katherine M.; Estes, Jaclyn L.; Rachel S. Gerber; Jovana P. Lekovich; Elias, Rony T.; Spandorfer, Steven D.
The human papillomavirus (HPV) is a sexually transmitted infection common among men and women across all geographic and socioeconomic subgroups worldwide. Recent evidence suggests that HPV infection may affect fertility and alter the efficacy of assisted reproductive technologies. In men, HPV infection can affect sperm parameters, specifically motility. HPV-infected sperm can transmit viral DNA to oocytes, which may be expressed in the developing blastocyst. HPV can increase trophoblastic apo...
Full Text Available Papillomaviruses have evolved over many millions of years to propagate themselves at specific epithelial niches in a range of different host species. This has led to the great diversity of papillomaviruses that now exist, and to the appearance of distinct strategies for epithelial persistence. Many papillomaviruses minimise the risk of immune clearance by causing chronic asymptomatic infections, accompanied by long-term virion-production with only limited viral gene expression. Such lesions are typical of those caused by Beta HPV types in the general population, with viral activity being suppressed by host immunity. A second strategy requires the evolution of sophisticated immune evasion mechanisms, and allows some HPV types to cause prominent and persistent papillomas, even in immune competent individuals. Some Alphapapillomavirus types have evolved this strategy, including those that cause genital warts in young adults or common warts in children. These strategies reflect broad differences in virus protein function as well as differences in patterns of viral gene expression, with genotype-specific associations underlying the recent introduction of DNA testing, and also the introduction of vaccines to protect against cervical cancer. Interestingly, it appears that cellular environment and the site of infection affect viral pathogenicity by modulating viral gene expression. With the high-risk HPV gene products, changes in E6 and E7 expression are thought to account for the development of neoplasias at the endocervix, the anal and cervical transformation zones, and the tonsilar crypts and other oropharyngeal sites. A detailed analysis of site-specific patterns of gene expression and gene function is now prompted.
Howley, P.M.; Broker, T.R.
This book contains nine sections, each consisting of several papers. The section headings are : Papillomaviruses and Human Genital Tract Diseases;Papillomaviruses and Human Cutaneous Diseases, Papillomaviruses and Human Oral and Laryngeal Diseases;Therapeutic Approaches to Papillomavirus Infections;Animal Papillomaviruses;Molecular Biology;Transcription, Replication, and Genome Organization;Epithelial Cell Culture;Papillomavirus Transformation;and Viral Vectors.
Grabowski, Mary K; Kong, Xiangrong; Gray, Ronald H; Serwadda, David; Kigozi, Godfrey; Gravitt, Patti E; Nalugoda, Fred; Reynolds, Steven J; Wawer, Maria J; Redd, Andrew D; Watya, Stephen; Quinn, Thomas C; Tobian, Aaron A R
The association between partner human papillomavirus (HPV) viral load and incident HPV detection in heterosexual couples is unknown. HPV genotypes were detected in 632 human immunodeficiency virus (HIV)-negative couples followed for 2 years in a male circumcision trial in Rakai, Uganda, using the Roche HPV Linear Array. This assay detects 37 genotypes and provides a semiquantitative measure of viral load based on the intensity (graded 1-4) of the genotype-specific band; a band intensity of 1 indicates a low genotype-specific HPV load, whereas an intensity of 4 indicates a high load. Using Poisson regression with generalized estimating equations, we measured the association between partner's genotype-specific viral load and detection of that genotype in the HPV-discordant partner 1 year later. Incident detection of HPV genotypes was 10.6% among men (54 of 508 genotype-specific visit intervals) and 9.0% among women (55 of 611 genotype-specific visit intervals). Use of male partners with a baseline genotype-specific band intensity of 1 as a reference yielded adjusted relative risks (aRRs) of 1.14 (95% confidence interval [CI], .58-2.27]) for incident detection of that genotype among women whose male partner had a baseline band intensity of 2, 1.75 (95% CI, .97-3.17) among those whose partner had an intensity of 3, and 2.52 (95% CI, 1.40-4.54) among those whose partner had an intensity of 4. Use of female partners with a baseline genotype-specific band intensity of 1 as a reference yielded an aRR of 2.83 (95% CI, 1.50-5.33) for incident detection of that genotype among men whose female partner had a baseline band intensity of 4. These associations were similar for high-risk and low-risk genotypes. Male circumcision also was associated with significant reductions in incident HPV detection in men (aRR, 0.53 [95% CI, .30-.95]) and women (aRR, 0.42 [95% CI, .23-.76]). In heterosexual couples, the genotype-specific HPV load in one partner is associated with the risk of new
van der Weele, Pascal; Meijer, Chris J L M; King, Audrey J
Human papillomavirus (HPV) is a strongly conserved DNA virus, high-risk types of which can cause cervical cancer in persistent infections. The most common type found in HPV-attributable cancer is HPV16, which can be subdivided into four lineages (A to D) with different carcinogenic properties. Studies have shown HPV16 sequence diversity in different geographical areas, but only limited information is available regarding HPV16 diversity within a population, especially at the whole-genome level. We analyzed HPV16 major variant diversity and conservation in persistent infections and performed a single nucleotide polymorphism (SNP) comparison between persistent and clearing infections. Materials were obtained in the Netherlands from a cohort study with longitudinal follow-up for up to 3 years. Our analysis shows a remarkably large variant diversity in the population. Whole-genome sequences were obtained for 57 persistent and 59 clearing HPV16 infections, resulting in 109 unique variants. Interestingly, persistent infections were completely conserved through time. One reinfection event was identified where the initial and follow-up samples clustered differently. Non-A1/A2 variants seemed to clear preferentially (P = 0.02). Our analysis shows that population-wide HPV16 sequence diversity is very large. In persistent infections, the HPV16 sequence was fully conserved. Sequencing can identify HPV16 reinfections, although occurrence is rare. SNP comparison identified no strongly acting effect of the viral genome affecting HPV16 infection clearance or persistence in up to 3 years of follow-up. These findings suggest the progression of an early HPV16 infection could be host related.IMPORTANCE Human papillomavirus 16 (HPV16) is the predominant type found in cervical cancer. Progression of initial infection to cervical cancer has been linked to sequence properties; however, knowledge of variants circulating in European populations, especially with longitudinal follow-up, is
De Vincenzo R
Full Text Available Rosa De Vincenzo,1 Carmine Conte,1 Caterina Ricci,1 Giovanni Scambia,1 Giovanni Capelli2 1Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, 2Department of Human Sciences, Society and Health, University of Cassino and Southern Lazio, Cassino, Italy Abstract: In this paper, we review the published evidence about the long-term efficacy of the available human papillomavirus (HPV vaccines and their safety profile. Two prophylactic HPV vaccines – bivalent (bHPV and quadrivalent (qHPV – are now available, and vaccination programs are being widely implemented, primarily targeting adolescent girls. Efficacy has been widely demonstrated for both vaccines. Since the risk of HPV exposure potentially persists throughout a woman’s sexual life, vaccine duration of protection is critical to overall effectiveness. Interpreting the results of long-term efficacy studies for the two HPV vaccines can be puzzling, due to the heterogeneity of studies, different methods used in the assessment of immunogenicity, histopathological and virological end points, and statistical power issues. Moreover, an immunologic correlate of protection has not yet been established, and it is unknown whether higher antibody levels will really result in a longer duration of protection. Disease prevention remains the most important measure of long-term duration of vaccine efficacy. To date, the longest follow-up of an HPV vaccine has been 9.4 years for the bHPV vaccine. Long-term follow-up for qHPV vaccine goes up to 8 years. The vaccine continues to be immunogenic and well tolerated up to 9 years following vaccination. All randomized controlled clinical trials of the bHPV and the qHPV vaccines provide evidence of an excellent safety profile. The most common complaint reported is pain in the injection site, which is self-limiting and spontaneously resolved. The incidence of systemic adverse events (AEs, serious
Full Text Available Abstract Background Human papillomavirus (HPV has a causal role in cervical cancer with almost half a million new cases occurring each year. Presence of the carcinogenic HPV is necessary for the development of the invasive carcinoma of the genital tract. Therefore, persistent infection with carcinogenic HPV causes virtually all cervical cancers. Some aspects of the molecular evolution of this virus, as the putative importance of recombination in its evolutionary history, are an opened current question. In addition, recombination could also be a significant issue nowadays since the frequency of co-infection with more than one HPV type is not a rare event and, thus, new recombinant types could be currently being generated. Results We have used human alpha-PV sequences from the public database at Los Alamos National Laboratory to report evidence that recombination may exist in this virus. A model-based population genetic approach was used to infer the recombination signal from the HPV DNA sequences grouped attending to phylogenetic and epidemiological information, as well as to clinical manifestations. Our results agree with recently published ones that use a different methodology to detect recombination associated to the gene L2. In addition, we have detected significant recombination signal in the genes E6, E7, L2 and L1 at different groups, and importantly within the high-risk type HPV16. The method used has recently been shown to be one of the most powerful and reliable procedures to detect the recombination signal. Conclusion We provide new support to the recent evidence of recombination in HPV. Additionally, we performed the recombination estimation assuming the best-fit model of nucleotide substitution and rate variation among sites, of the HPV DNA sequence sets. We found that the gene with recombination in most of the groups is L2 but the highest values were detected in L1 and E6. Gene E7 was recombinant only within the HPV16 type. The
Pedersen, C.; Petaja, T.; Strauss, G.; Rumke, H.C.; Poder, A.; Richardus, J.H.; Spiessens, B.; Descamps, D.; Hardt, K.; Lehtinen, M.; Dubin, G.
PURPOSE: In female individuals 15-25-years of age, the AS04-containing human papillomavirus (HPV)-16/18 vaccine is highly immunogenic and provides up to 100% protection against HPV-16/18 persistent infection and associated cervical lesions up to 4.5 years. Optimal cervical cancer prevention will
Full Text Available Background: Molecular tests allow the detection of high-risk human papillomavirus in cervical samples, playing an important role in the prevention of cervical cancer. Objectives: We performed a study to determine the prevalence of HPV 16, HPV 18 and other high-risk human papillomavirus (pool 12 genotypes in Peruvian females from diverse urban areas using the cobas 4800 HPV test. Methods: Routine cervical samples collected in our laboratory were analyzed by cobas 4800 HPV test. Results: A total of 2247 samples from female patients aged 17–79 years were tested. high-risk human papillomavirus was positive in 775 (34.49% samples. Of these, 641 (82.71% were single infections and 134 (17.29% were multiple infections. The positivity rates for HPV 16, HPV 18, and other high-risk human papillomavirus were 10.77%, 2.0%, and 28.08%, respectively. In multiple high-risk human papillomavirus infections, the concomitance of HPV 16 and other high-risk human papillomavirus was more prevalent (13.42%. Conclusion: Our study showed high prevalence of high-risk human papillomavirus in urban Peru, mainly among young women. In both single and multiple infections other high-risk human papillomavirus were more prevalent than HPV 16 and HPV 18, which might influence vaccine impact in our country. Furthermore, the cobas 4800 HPV test may be considered a useful tool for HPV molecular diagnosis.
... in its entirety from the CDC HPV (Human Papillomavirus) Vaccine - Gardasil® Vaccine Information Statement (VIS): www.cdc. ... WHAT IS HPV? Genital human papillomavirus (HPV) is the most common ... United States. More than half of sexually active men and women ...
... in its entirety from the CDC HPV (Human Papillomavirus) Cervarix® Vaccine Information Statement: www.cdc.gov/vaccines/ ... WHAT IS HPV? Genital human papillomavirus (HPV) is the most common ... United States. More than half of sexually active men and women ...
Conclusion: Our study showed high prevalence of high-risk human papillomavirus in urban Peru, mainly among young women. In both single and multiple infections other high-risk human papillomavirus were more prevalent than HPV 16 and HPV 18, which might influence vaccine impact in our country. Furthermore, the cobas 4800 HPV test may be considered a useful tool for HPV molecular diagnosis.
Iwasaki, Ricardo; Galvez-Philpott, Felipe; Arias-Stella, Javier; Arias-Stella, Javier
Molecular tests allow the detection of high-risk human papillomavirus in cervical samples, playing an important role in the prevention of cervical cancer. We performed a study to determine the prevalence of HPV 16, HPV 18 and other high-risk human papillomavirus (pool 12 genotypes) in Peruvian females from diverse urban areas using the cobas 4800 HPV test. Routine cervical samples collected in our laboratory were analyzed by cobas 4800 HPV test. A total of 2247 samples from female patients aged 17-79 years were tested. high-risk human papillomavirus was positive in 775 (34.49%) samples. Of these, 641 (82.71%) were single infections and 134 (17.29%) were multiple infections. The positivity rates for HPV 16, HPV 18, and other high-risk human papillomavirus were 10.77%, 2.0%, and 28.08%, respectively. In multiple high-risk human papillomavirus infections, the concomitance of HPV 16 and other high-risk human papillomavirus was more prevalent (13.42%). Our study showed high prevalence of high-risk human papillomavirus in urban Peru, mainly among young women. In both single and multiple infections other high-risk human papillomavirus were more prevalent than HPV 16 and HPV 18, which might influence vaccine impact in our country. Furthermore, the cobas 4800 HPV test may be considered a useful tool for HPV molecular diagnosis. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.
Comparison of the AdvanSure Human Papillomavirus Screening Real-Time PCR, the Abbott RealTime High Risk Human Papillomavirus Test, and the Hybrid Capture Human Papillomavirus DNA Test for the Detection of Human Papillomavirus
Hwang, Yusun; Lee, Miae
Background We evaluated the performance of various commercial assays for the molecular detection of human papillomavirus (HPV); the recently developed AdvanSure HPV Screening real-time PCR assay (AdvanSure PCR) and the Abbott RealTime High Risk HPV PCR assay (Abbott PCR) were compared with the Hybrid Capture 2 HPV DNA Test (HC2). Methods All 3 tests were performed on 177 samples, and any sample that showed a discrepancy in any of the 3 tests was genotyped using INNO-LiPA HPV genotyping and/or...
Vallely, Lorraine A; Roberts, Stephen A; Kitchener, Henry C; Brabin, Loretta
With the introduction of human papillomavirus (HPV) vaccination an evidence base on effective adolescent educational interventions is urgently required. We undertook formative research to develop and evaluate a film on HPV and cervical cancer prevention for school children who will be offered HPV vaccination in the UK. The main outcome measures were the number of children allowed by parents to view the film and children's knowledge. Our results indicated that the film's four key messages were acceptable to parents and largely understood by adolescents but these messages will need reinforcing if the full potential of a prophylactic vaccine is to be realised.
Nath, Amiya Kumar; Thappa, Devinder Mohan
This article takes a critical look at the pros and cons of human papillomavirus (HPV) vaccines. There is enough evidence to suggest that the prophylactic vaccines are efficacious in preventing various benign and malignant conditions (including cervical cancers) caused by HPV. Even though the vaccine is costly, hypothetical analysis has shown that HPV vaccination will be cost effective in the long run. Therapeutic HPV vaccines used to treat established disease are still undergoing evaluation in clinical studies, and results seem to be encouraging. Although several countries have started mandatory vaccination programs with the prophylactic HPV vaccines, conservatives have voiced concerns regarding the moral impact of such vaccination programs.
Patricia Caseiro Silverio
Full Text Available Porokeratoma is a rare, relatively newly described and still unclear entity. Here, we describe the case of a 52-year-old male patient who presented with four well-defined, verrucous and hyperkeratotic lesions. Microscopically, one of the lesions showed acanthopapillomatosis overlying compact orthokeratosis. Prominent broad and confluent cornoid lamellae were present, with no granular layer and some dyskeratotic keratinocytes. PCR sequencing and in situ hybridization revealed the presence of human papillomavirus (HPV type 16 in the lesion. The association of porokeratoma and HPV infection has not previously been reported.
Balog, Joseph E
Compulsory human papillomavirus (HPV) vaccination of young girls has been proposed as a public health intervention to reduce the threat of the disease. Such a program would entail a symbiotic relationship between scientific interests in reducing mortality and morbidity and philosophical interests in promoting morality. This proposal raises the issue of whether government should use its police powers to restrict liberty and parental autonomy for the purpose of preventing harm to young people. I reviewed the scientific literature that questions the value of a HPV vaccination. Applying a principle-based approach to moral reasoning, I concluded that compulsory HPV vaccinations can be justified on moral, scientific, and public health grounds.
Melbye, M; Frisch, M
There is substantial evidence to suggest that common risk factors exist for cancer of the cervix and other anogenital cancers. Cervical cancer has been etiologically linked with venereal types of human papillomavirus (HPV) and the same types of HPV are being found in other anogenital tissues. The question is to what extent these HPV types may also contribute to carcinogenesis in anogenital cancer other than cervical cancer. In this review some general aspects of the natural history of HPV are presented followed by a description of the incidence and risk factors for anal, vulvar, and penile cancer. Main focus is given to the evidence for an association between these cancers and HPV.
Pascal van der Weele
Full Text Available Background: The most commonly found human papillomavirus (HPV types in cervical cancer are HPV16 and HPV18. Genome variants of these types have been associated with differential carcinogenic potential. To date, only a handful of studies have described HPV18 whole genome sequencing results. Here we describe HPV18 variant diversity and conservation of persistent infections in a longitudinal retrospective cohort study. Methods: Cervical self-samples were obtained annually over four years and genotyped on the SPF10-DEIA-LiPA25 platform. Clearing and persistent HPV18 positive infections were selected, amplified in two overlapping fragments, and sequenced using 32 sequence primers. Results: Complete viral genomes were obtained from 25 participants with persistent and 26 participants with clearing HPV18 infections, resulting in 52 unique HPV18 genomes. Sublineage A3 was predominant in this population. The consensus viral genome was completely conserved over time in persistent infections, with one exception, where different HPV18 variants were identified in follow-up samples. Conclusions: This study identified a diverse set of HPV18 variants. In persistent infections, the consensus viral genome is conserved. The identification of only one HPV18 infection with different major variants in follow-up implies that this is a potentially rare event. This dataset adds 52 HPV18 genome variants to Genbank, more than doubling the currently available HPV18 information resource, and all but one variant are unique additions.
Golovina, D A; Trofimova, O B; Ermilova, V D; Matveev, V B; Volgareva, G M
A battery of tests for detection human papillomavirus DNA, mRNA corresponding to viral oncogenes, and viral oncoprotein E7 in cancer bladder urothelium was piloted in 35 samples of bladder cancer. DNA of human papillomavirus type 16 (causes cervical cancer) was found in 16 (46%) samples; E6/E7 oncogene transcript and E7 oncoprotein of human papillomavirus type 16 were detected in 10 and 7 human papillomavirus DNA-positive samples, respectively. These findings attest to association of bladder cancer with human papillomavirus in Russia.
Cano Garfias, R; Villarreal Peral, C; Juárez Azpilcueta, A
A prospective and transversal study in 100 patients since January to December of 1994, was done, to know the human papiloma virus infection prevalence in male genitals. The patients were studied by a clinical history, genital area colposcopic revision after acetic acid 5% application, biopsy of the lesion and histopathology study. The patients age was among 16 to 71 years old, with a media of 38.8 years old. The sexual activity beginning was from 12 to 27 years old, with an average of 18 years old. Forty one percent of the patients have had sexual relations with prostitutes, 26% have had sexually transmitted diseases, 9% of the patients referred only 1 sexual mate and 82% had human papiloma virus infection.
Turki, Rola; Sait, Khalid; Anfinan, Nisreen; Sohrab, Sayed Sartaj; Abuzenadah, Adel Mohammed
Human papillomavirus (HPV) infection is the main causes of cervical cancer in women worldwide. The goal of the present study was to determine the prevalence and distribution of HPV genotypes in women from Saudi Arabia. Recently, several HPV detection methods have been developed, each with different sensitivities and specificities. In this study, total forty cervical samples were subjected to polymerase chain reaction and hybridization to BioFilmChip microarray assessment. Human papillomavirus (HPV) infections were found in 43% of the specimens. The most prevalent genotypes were HPV 16 (30%) HPV 18 (8.0%) followed by type HPV 45, occurring at 5.0%. Our finding showed the HPV infection and prevalence is increasing at alarming rate in women of Saudi Arabia. There was no low risk infection detected in the tested samples. The BioFilmChip microarray detection system is highly accurate and suitable for detection of single and multiple infections, allowing rapid detection with less time-consumption and easier performance as compared with other methods.
Loran, O B; Sinyakova, L A; Gundorova, L V; Kosov, V A; Kosova, I V; Pogodina, I E; Kolbasov, D N
To determine the role of human papillomavirus (HPV) of high oncogenic risk in the development of urinary bladder cancer. 100 patients (72 men and 28 women) aged 38 to 90 years (mean age 65+/-10 years) diagnosed with bladder cancer were examined and underwent treatment. Clinical assessment was complemented by enzyme-linked immunosorbent assays for the presence of antiviral antibodies to herpes simplex virus (HSV) type 1 and type 2, cytomegalovirus (CMV), Epstein-Barr virus (EBV), urethra scraping for detecting high oncogenic risk HPV. Tumor tissue was sampled for PCR virus detection. Semi-quantitative analysis was used to evaluate the components of lymphocyte-plasmocyte and leukocyte infiltrates and cytopathic changes in tumor tissue. There were positive correlations between cytopathic cell changes (koylocytosis and intranuclear inclusions, as manifestations of HPV) and the level of antiviral antibodies, the presence of viruses in the tumor, as well as with the components of the lymphoid-plasmocyte infiltrate. Negative correlations were found between the presence of papillomatosis and the above changes. Human papillomavirus is believed to be a trigger for the initiation of a tumor in young patients with a latent infection (CMV and EBV, HSV, HPV). Cytopathic changes (kylocytosis and intranuclear inclusions) were associated with the activity and morphological features of herpes-viral infections. Their degree varied depending on the stage of the process, but not on the anaplasia degree. Papillomatosis is associated with a more favorable course of the tumor process.
Malik, Heena; Khan, Fahim H; Ahsan, Haseeb
An association between human papillomavirus (HPV) infection and the development of cervical cancer was initially suggested over 30 years ago, and today there is clear evidence that certain subtypes of HPV are the causative agents of such malignancies. Papillomaviruses make up a vast family that comprises hundreds of different viruses. These viruses infect epithelia in humans and animals and cause benign hyperproliferative lesions, commonly called warts or papillomas, which can occasionally progress to squamous cell cancer. HPV infections are considered the most common among sexually transmitted diseases. One of the most prevalent cancer types induced by HPV (mostly types 16 and 18) is cervical cancer. Vaccination is the most effective means of preventing this infectious disease. These prophylactic vaccines, based on virus-like particles (VLPs), are extremely effective in providing protection from infection in almost 100 % of cases. VLP vaccines of HPV are subunit vaccines consisting only of the major viral capsid protein of HPV. There are two types of vaccine available: bivalent vaccine (against HPV-16/18) and quadrivalent vaccine (against HPV-6/11/16/18). Second-generation prophylactic HPV vaccines, currently in clinical trials, may hold several merits over the current bivalent and quadrivalent vaccines, such as protection against additional oncogenic HPV types, less dependence on cold-chain storage and distribution, and non-invasive methods of delivery.
Kumar, Satish; Jena, Lingaraja; Daf, Sangeeta; Mohod, Kanchan; Goyal, Peyush; Varma, Ashok K
Human papillomavirus (HPV) infection is the leading cause of cancer mortality among women worldwide. The molecular understanding of HPV proteins has significant connotation for understanding their intrusion in the host and designing novel protein vaccines and anti-viral agents, etc. Genomic, proteomic, structural, and disease-related information on HPV is available on the web; yet, with trivial annotations and more so, it is not well customized for data analysis, host-pathogen interaction, strain-disease association, drug designing, and sequence analysis, etc. We attempted to design an online reserve with comprehensive information on HPV for the end users desiring the same. The Human Papillomavirus Proteome Database (hpvPDB) domiciles proteomic and genomic information on 150 HPV strains sequenced to date. Simultaneous easy expandability and retrieval of the strain-specific data, with a provision for sequence analysis and exploration potential of predicted structures, and easy access for curation and annotation through a range of search options at one platform are a few of its important features. Affluent information in this reserve could be of help for researchers involved in structural virology, cancer research, drug discovery, and vaccine design.
Full Text Available Human papillomavirus (HPV infection is the leading cause of cancer mortality among women worldwide. The molecular understanding of HPV proteins has significant connotation for understanding their intrusion in the host and designing novel protein vaccines and anti-viral agents, etc. Genomic, proteomic, structural, and disease-related information on HPV is available on the web; yet, with trivial annotations and more so, it is not well customized for data analysis, host-pathogen interaction, strain-disease association, drug designing, and sequence analysis, etc. We attempted to design an online reserve with comprehensive information on HPV for the end users desiring the same. The Human Papillomavirus Proteome Database (hpvPDB domiciles proteomic and genomic information on 150 HPV strains sequenced to date. Simultaneous easy expandability and retrieval of the strain-specific data, with a provision for sequence analysis and exploration potential of predicted structures, and easy access for curation and annotation through a range of search options at one platform are a few of its important features. Affluent information in this reserve could be of help for researchers involved in structural virology, cancer research, drug discovery, and vaccine design.
Ogunmodede, Folashade; Yale, Steven H.; Krawisz, Bruce; Tyler, Gregory C.; Evans, Anthony C.
Cervical cancer continues to be a leading cause of mortality worldwide. The incidence and mortality associated with invasive cervical cancer have declined significantly in developed countries due to widespread availability of screening with the Papanicolaou (Pap) test. However, the incidence and prevalence of non-invasive cervical intraepithelial neoplasms and genital warts related to oncogenic and nononcogenic strains of human papilloma viruses (HPV) have remained relatively stable. Recent advances in molecular diagnostics have resulted in improved characterization of various HPV types and have led to changes in terminology of Pap test findings. Changes in nomenclature may lead to confusion among primary care providers regarding how best to further evaluate abnormal cytological results. This article provides a concise overview of the approach to the treatment of genital warts and management of abnormal cervical cytology based on guidelines from the American Society of Colposcopy and Cervical Pathology. It also reviews advances in HPV vaccine development and the new recombinant vaccine recently approved for use in the United States. PMID:18086908
Graham, Sheila V; Faizo, Arwa Ali A
Human papillomaviruses possess circular double stranded DNA genomes of around 8kb in size from which multiple mRNAs are synthesized during an infectious life cycle. Although at least three viral promoters are used to initiate transcription, viral mRNAs are largely the product of processing of pre-mRNAs by alternative splicing and polyadenylation. The HPV life cycle and viral gene expression are tightly linked to differentiation of the epithelium the virus infects: there is an orchestrated production of viral mRNAs and proteins. In this review we describe viral mRNA expression and the roles of the SR and hnRNP proteins that respectively positively and negatively regulate splicing. We discuss HPV regulation of splicing factors and detail the evidence that the papillomavirus E2 protein has splicing-related activities. We highlight the possibility that HPV-mediated control of splicing in differentiating epithelial cells may be necessary to accomplish the viral replication cycle. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
Miguel A. Serra Valdés
Full Text Available Introduction. Currently over 216 types of human papillomavirus (HPV have been reported, but only 100 have been fully sequenced. They are able to infect cells of the basal layer of any epithelium. Evidence of HPV oncogenicity has been found. Objective. To describe a case of esophageal HPV infection associated to cancer of the esophagus. Case report. 63 years-old, African and rural origin, single, female housewife with the habit of smoking and frequent ingestion of alcohol. Four months before the diagnosis was established, the patient began to gradually develop dysphagia to solids and weight loss. Upper endoscopy shows a proliferative ulcerated lesion in the middle third of the esophagus. Biopsy is consistent with esophageal squamous cell carcinoma. Cytology is suggestive of papillomavirus infection. Discussion. Prior esophageal papillomatosis and other risk factors contributed to the occurrence of esophageal carcinoma. Histopathology was consistent with the diagnosis of squamous cell carcinoma probably caused by HPV infection. Conclusion. The association between papilloma virus and esophageal cancer is rare but can be diagnosed if it is suspected and other risk factors are present, as well as if there is access to modern diagnostic means.
Poljak, Mario; Šterbenc, Anja; Lunar, Maja M
In comparison to their HIV-negative counterparts, people living with HIV (PLWH) have a higher prevalence of human papillomavirus (HPV) infection in various anatomical sites coupled with increased HPV persistence, higher risk of HPV-related tumors, and faster disease progression. Areas covered: Gender-neutral prevention strategies for HPV-related cancers in PLWH discussed: ABC approach, HPV vaccination, antiretroviral treatment (ART), anal cancer screening, and smoking cessation. Gender specific strategies: cervical cancer screening reduces the incidence and mortality of cervical cancer and circumcision might reduce the risk of HPV infections in men. Expert commentary: HPV-related cancer incidence has not declined (e.g. cervical cancer) and has even increased (e.g. anal cancer) in the ART era, demanding an effective HPV prevention strategy. HPV vaccination should be introduced into national prevention programs worldwide immediately because current prophylactic vaccines are safe, tolerable, and immunogenic in PLWH. HPV vaccine efficacy trials in PLWH are essential to determine the most appropriate immunization schedule. The population most at risk of anal cancer is HIV-positive men who have sex with men, who are not protected by herd immunity if only the female population is vaccinated. Unvaccinated PLWH need enhanced surveillance for early detection of HPV-related cancers and their precursors.
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
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
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
Full Text Available Human papillomaviruses (HPV infect cutaneous and mucosal epithelia and induce benign and malignant lesions. Non-melanoma skin cancer (NMSC, encompassing basal cell carcinoma and squamous cell carcinoma (SCC, is the most frequent cancer in the Caucasian population, and the incidence has increased dramatically worldwide. Ultraviolet (UV radiation is a major risk factor for NMSC, and cutaneous HPV is also considered to play an active role during the pathogenesis of these cancers. The first evidence for the involvement of HPV in NMSC was reported in patients with Epidermodysplasia verruciformis (EV. HPV types detected in skin tumours of these patients are referred to as EV/cutaneous HPV types belonging to the beta- and gamma-papillomaviruses (PV. Epidemiological studies have shown a higher risk of several EV/cutaneous HPV types for NMSC. Furthermore, in vitro and animal models show transforming properties of some PV types. The anti-apoptotic activities, and the delay of DNA repair mechanism caused by some EV/cutaneous HPV E6 proteins in response to UV-induced mutations, may lead to the persistence of DNA-damaged keratinocytes. Thus, specific EV/cutaneous HPV types as co-factors in association with UV-radiation and the immune system seem to be involved in the early pathogenesis of cutaneous SCC.
Mbulawa, Zizipho Z A; Coetzee, David; Marais, Dianne J; Kamupira, Mercy; Zwane, Eugene; Allan, Bruce; Constant, Deborah; Moodley, Jennifer R; Hoffman, Margaret; Williamson, Anna-Lise
This study examined the concordance of genital human papillomavirus (HPV) infection in 254 heterosexually active couples and the impact of HIV coinfection. Genital HPV detection was significantly more common among HIV-infected women than among HIV-seronegative women (99 [68%] of 145 women vs. 33 [31%] of 107 women; P HPV detection was significantly more common among HIV-infected men than among HIV-seronegative men (67 [72%] of 93 and 65 [43%] of 150 men, respectively; P women had a significantly greater prevalence of HPV infection than did HIV-seronegative male partners of HIV-seronegative women (38 [58%] of 65 men vs. 27 [32%] of 85 men; P = .001), indicating that HIV coinfection in one partner has a significant impact on the prevalence of HPV genital infection in the other partner. HPV concordance between couples was associated with HIV infection status (P HPV was associated with HIV concordance status (P = .024). HIV-seronegative couples were more likely to share 1 HPV type and were unlikely to share >1 type, whereas HIV-infected or HIV-discordant couples were more likely to share >1 HPV type. Women with a high HPV load frequently shared HPV types with their male partners, suggesting that a high HPV load may play a role in HPV transmission between partners. In conclusion, HIV coinfection in one or both sexually active partners increased HPV prevalence and HPV type-specific concordance.
Colbère-Garapin, F; Jacques, S; Drillet, A S; Pavio, N; Couderc, T; Blondel, B; Pelletier, I
Poliovirus (PV) can persist in vivo in the intestine of immunocompromised hosts for years. Moreover, immunocompetent individuals who have survived paralytic poliomyelitis sometimes develop the post-poliomyelitis syndrome (PPS), consisting of a variety of symptoms including new muscular atrophies. PPS may be due to PV persistence. We have developed models of PV persistence in neural cells and epidermoid cells. Cell determinants are of crucial importance for the establishment of persistent infections in human neuronal cells, whereas viral determinants play the primary role in human epidermoid HEp-2 cells. The results obtained with these in vitro models show the capacity of PV to persist and reveal a virus and cell co-evolution involving PV-receptor interactions. In addition, they suggest that several mechanisms are used by PV to establish and maintain persistent infections.
Cortés-Bordoy, Javier; Martinón-Torres, Federico
Successful implementation of Human Papillomavirus (HPV) vaccine in each country can only be achieved from a complementary and synergistic perspective, integrating all the different points of view of the diverse related professionals. It is this context where the Spanish HPV Vaccine Consensus Group (Grupo Español de Consenso sobre la Vacuna VPH, GEC-VPH) was created. GEC-VPH philosophy, objectives and experience are reported in this article, with particular attention to the management of negative publicity and anti-vaccine groups. Initiatives as GEC-VPH--adapted to each country's particular idiosyncrasies--might help to overcome the existing barriers and to achieve wide and early implementation of HPV vaccination.
Saslow, Debbie; Andrews, Kimberly S.; Manassaram-Baptiste, Deana; Loomer, Lacey; Lam, Kristina E.; Fisher-Borne, Marcie; Smith, Robert A.; Fontham, Elizabeth T. H.
The American Cancer Society (ACS) reviewed and updated its guideline on human papillomavirus (HPV) vaccination based on a methodologic and content review of the Advisory Committee on Immunization Practices (ACIP) HPV vaccination recommendations. A literature review was performed to supplement the evidence considered by the ACIP and to address new vaccine formulations and recommendations as well as new data on population outcomes since publication of the 2007 ACS guideline. The ACS Guideline Development Group determined that the evidence supports ACS endorsement of the ACIP recommendations, with one qualifying statement related to late vaccination. The ACS recommends vaccination of all children at ages 11 and 12 years to protect against HPV infections that lead to several cancers and precancers. Late vaccination for those not vaccinated at the recommended ages should be completed as soon as possible, and individuals should be informed that vaccination may not be effective at older ages. PMID:27434803
Cervical cancer remains a major cause of morbidity and mortality for women worldwide. Although the introduction of comprehensive screening programs has reduced the disease incidence in developed countries, it remains a major problem in the developing world. The recent licensing of 2 vaccines against human papillomavirus (HPV) type 16 and HPV-18, the viruses responsible for 70% of cervical cancer cases, offers the hope of disease prevention. In this article, we review the role of HPV in the etiology of cervical cancer and the evidence to support the introduction of vaccination programs in young women and discuss the potential obstacles to widespread vaccination. In addition, we discuss the issues that remain to be elucidated, including the potential need for booster doses of the vaccine and the role of concomitant vaccination in men.
Baussano, Iacopo; Lazzarato, Fulvio; Brisson, Marc; Franceschi, Silvia
Human papillomavirus (HPV) prevalence varies widely worldwide. We used a transmission model to show links between age-specific sexual patterns and HPV vaccination effectiveness. We considered rural India and the United States as examples of 2 heterosexual populations with traditional age-specific sexual behavior and gender-similar age-specific sexual behavior, respectively. We simulated these populations by using age-specific rates of sexual activity and age differences between sexual partners and found that transitions from traditional to gender-similar sexual behavior in women sexual behavior and that increased risk for HPV infection attributable to transition is preventable by early vaccination. Our study highlights the importance of using time-limited opportunities to introduce HPV vaccination in traditional populations before changes in age-specific sexual patterns occur.
Sjö, Nicolai Christian; von Buchwald, Christian; Cassonnet, Patricia
PURPOSE: Epithelial tumours of the lacrimal sac are rare but important entities that may carry grave prognoses. In this study the prevalence and possible role of human papillomavirus (HPV) infection in epithelial tumours of the lacrimal sac were evaluated. METHODS: Five papillomas and six...... 11 RNA was demonstrated in two papillomas. CONCLUSIONS: By analysing 11 epithelial lacrimal sac papillomas and carcinomas using PCR, DNA ISH and RNA ISH, we found HPV DNA in all investigated transitional epithelium tumours of the lacrimal sac. HPV RNA was present in two of eight epithelial lacrimal...... sac tumours positive for HPV DNA. As RNA degrades fast in paraffin-embedded tissue, only a small fraction of DNA-positive tumours can be expected to be RNA-positive. We therefore suggest that HPV infection is associated with the development of lacrimal sac papillomas and carcinomas....
Thomas, Tami L; Stephens, Dionne P; Johnson-Mallard, Versie; Higgins, Melinda
This exploratory descriptive study examined perceived vulnerabilities to human papillomavirus (HPV) and the correlation to factors influencing vaccine beliefs and vaccine decision making in young Hispanic males attending a large public urban university. Only 24% of participants believed that the HPV vaccine could prevent future problems, and 53% said they would not be vaccinated. The best predictors of HPV vaccination in young Hispanic men were agreement with doctor recommendations and belief in the vaccine's efficacy. Machismo cultural norms influence young Hispanic men's HPV-related decision making, their perceptions of the vaccine, and how they attitudinally act on what little HPV information they have access to. This study provides culturally relevant information for the development of targeted health education strategies aimed at increasing HPV vaccination in young Hispanic men. © The Author(s) 2014.
Boulet, Gaëlle; Horvath, Caroline; Vanden Broeck, Davy; Sahebali, Shaira; Bogers, Johannes
The recognition of a causal relationship between human papillomaviruses and cancer almost 30 years ago led to a rapid expansion of knowledge in the field, resulting in the description of the main mediators of HPV-induced carcinogenesis, the viral proteins E6 and E7. These oncoproteins show a remarkable pleiotropism in binding host-cell proteins, with the tumour suppressor genes p53 and pRb as their major targets. These interactions induce proliferation, immortalization and malignant transformation of infected cells. The link between HPV and cervical cancer led to the development of molecular methods, often based on the detection of E6 and E7, for screening and diagnosis. Therapeutic vaccines and gene therapy are primarily directed at E6 and E7. Although prophylactic vaccines are available, further understanding of the viral life cycle and the mechanisms underlying HPV-induced oncogenesis is necessary to face the many challenges in the field of HPV and cancer.
Vichnin, Michelle; Bonanni, Paolo; Klein, Nicola P
BACKGROUND: A quadrivalent human papillomavirus (HPV4) type 6/11/16/18 vaccine (GARDASIL/SILGARD®) has been licensed in many countries around the world for the prevention of cervical, vulvar, vaginal, and anal cancers and precancers, as well as external genital warts causally related to HPV types 6....../11/16/18. Across 7 phase 3 clinical trials involving more than 29,000 males and females ages 9-45 years, vaccination was generally well tolerated. Because of its expected public health benefit in reducing cervical cancer and other HPV-related diseases, the vaccine has been implemented in the national vaccination...... programs of several countries, with over 178 million doses distributed worldwide. METHODS: Extensive efforts to assess the safety of the vaccine in routine practice have been conducted over the past 9 years since licensure, including more than 15 studies in more than 1 million preadolescents, adolescents...
de Casadevante, Victoria Fernández; Cuesta, Julita Gil; Cantarero Arevalo, Lourdes
Background: Cervical cancer is the fourth most common cancer affecting women worldwide. Since 2006, two human papillomavirus vaccines (HPVV) have been licensed to protect women against the virus that causes cervical cancer. However, worldwide coverage remains unequal. Studies from the USA found...... refers to either initiation and/or completion of the three dose vaccination program. Results: Out of the 23 eligible studies, 14 were retrospective reviews of data, six were cross-sectional surveys, and three were prospective cohort studies. Higher HPVV uptake was associated with ethnic majority...... populations, higher socio-economic status, regular cervical screening participation by the mother, and having received previous childhood vaccinations. Conclusion: Since the vaccine is offered for free in most of the European countries, the findings suggest that ethno-cultural and educational factors play...
Garland, Suzanne M; Kjaer, Susanne K.; Muñoz, Nubia
Prophylactic human papillomavirus (HPV) vaccination programs constitute major public health initiatives worldwide. We assessed the global effect of quadrivalent HPV (4vHPV) vaccination on HPV infection and disease. PubMed and Embase were systematically searched for peer-reviewed articles from...... January 2007 through February 2016 to identify observational studies reporting the impact or effectiveness of 4vHPV vaccination on infection, anogenital warts, and cervical cancer or precancerous lesions. Over the last decade, the impact of HPV vaccination in real-world settings has become increasingly...... evident, especially among girls vaccinated before HPV exposure in countries with high vaccine uptake. Maximal reductions of approximately 90% for HPV 6/11/16/18 infection, approximately 90% for genital warts, approximately 45% for low-grade cytological cervical abnormalities, and approximately 85...
Full Text Available Human papillomavirus (HPV, a sexually transmitted DNA virus that can lead to cervical cancer, is the most common cancer among women in developing regions. More than 270,000 women die per year from cervical cancer globally, and 85% of those deaths occur in developing countries. In the past, many low- and middle-income countries (LMICs have been unable to afford the implementation of HPV vaccination programmes, resulting in high cervical cancer mortality rates. Gavi, an organisation created to improve worldwide access to vaccines, undertook an initiative that had the goal of decreasing the price of an HPV vaccine to under $5 and increasing access for adolescent girl populations in LMICs. This was done through market shaping, co-financing and implementation support. This case study will present and evaluate Gavi's intervention by assessing targets, investigating cost-effectiveness and identifying strategic challenges.
Reisinger, Keith S; Block, Stan L; Lazcano-Ponce, Eduardo; Samakoses, Rudiwilai; Esser, Mark T; Erick, Joanne; Puchalski, Derek; Giacoletti, Katherine E D; Sings, Heather L; Lukac, Suzanne; Alvarez, Frances B; Barr, Eliav
Administration of a quadrivalent HPV-6/ 1/16/18 vaccine to 16- to 26-year-old women was highly effective in preventing HPV-6/ 1/16/18-related cervical/vulvar/vaginal precancerous lesions and genital warts. As the risk of acquiring HPV significantly rises after sexual debut, HPV vaccines should have the greatest benefit in sexually naive adolescents. We evaluated the tolerability and immunogenicity of quadrivalent vaccine in males and females 9 to 15 years of age through 18 months postenrollment. In this randomized, double-blind trial, 1781 sexually naive children were assigned (2:1) to quadrivalent HPV-6/11/16/18 vaccine or saline placebo administered at day 1 and months 2 and 6. Serum neutralizing anti-HPV-6/11/16/18 responses were summarized as geometric mean titers (GMTs) and seroconversion rates. Primary analyses were done per-protocol (subjects received 3 doses, had no major protocol violations and were HPV type-specific seronegative at day 1). Adverse experiences were collected by diary card. At month 7, seroconversion rates were > or =99.5% for the 4 vaccine-HPV-types. GMTs and seroconversion rates in boys were noninferior to those in girls (P or =91.5% of vaccine recipients were seropositive, regardless of gender. A higher proportion of vaccine recipients (75.3%) than placebo recipients (50.0%) reported one or more injection-site adverse experiences following any vaccination. Rates of fever were similar between vaccination groups. No serious vaccine-related adverse experiences were reported. In 9- to 15-year-old adolescents, the quadrivalent vaccine was generally well tolerated and induced persistent anti-HPV serologic responses in the majority of subjects for at least 12 months following completion of a three-dose regimen. The vaccine durability supports universal HPV vaccination programs in adolescents to reduce the burden of clinical HPV disease, particularly cervical cancer and precancers.
Full Text Available Introduction : Genital human papillomavirus (HPV infections are essentials factors in the development of cervical cancer. Human papillomavirus vaccines can contribute to reducing the high incidence of this disease, provided that this form of prophylaxis is commonly accepted. Participation in vaccinations is restricted by the belief that their implementation and consequent feeling of safety will reduce women’s participation in other forms of cervical carcinoma prophylaxis and will encourage them to be sexually promiscuous. Aim of the research study : To determine the awareness of cervical carcinoma prophylaxis among young women vaccinated against HPV by comparing them with a group of unvaccinated women. Material and methods: The survey covered a group of 210 young women in the age range 18 to 20 years, who were vaccinated against HPV. Within the framework of comparison, the survey covered a group of 255 young HPV-unvaccinated women, adequately selected in respect of age and education. Results: The HPVvaccinated women declared participation in medical check-ups and cytological tests no less frequently than the unvaccinated women. In both groups, the usage of condoms, sexual partners hygiene, monogamy and smoking abstinence were determined as behaviours limiting the occurrence of cervical carcinoma. Conclusions: Awareness of the application of supplementary prophylaxis of cervical carcinoma was high among the HPV vaccinated woman and did not differ from the unvaccinated woman’s awareness. Young women did not show a tendency for promiscuous behaviours, and were more likely touse condoms in the prevention of cervical carcinoma than were the unvaccinated woman.
Holl, Katsiaryna; Nowakowski, Andrzej M; Powell, Ned
Cervical glandular neoplasias (CGN) present a challenge for cervical cancer prevention due to their complex histopathology and difficulties in detecting preinvasive stages with current screening practices. Reports of human papillomavirus (HPV) prevalence and type-distribution in CGN vary, providi...
Rebolj, M; Njor, Sisse Helle; Lynge, E.
OBJECTIVE: We studied how representative cytologically abnormal women ("referral populations") are with respect to uncovering differences between human papillomavirus (HPV) assays in the primary screening where most women are cytologically normal. METHODS: A total of 4997 women were tested...
Wakae, Kousho; Aoyama, Satoru; Wang, Zhe; Kitamura, Kouichi; Liu, Guangyan; Monjurul, Ahasan Md; Koura, Miki; Imayasu, Mieko; Sakamoto, Naoya; Nakamura, Mitsuhiro; Kyo, Satoru; Kondo, Satoru; Fujiwara, Hiroshi; Yoshizaki, Tomokazu; Kukimoto, Iwao; Yamaguchi, Katsushi; Shigenobu, Shuji; Nishiyama, Tomoaki; Muramatsu, Masamichi
Human papillomavirus type 16 (HPV16) is a major cause of cervical cancer. We previously demonstrated that C-to-T and G-to-A hypermutations accumulated in the HPV16 genome by APOBEC3 expression in vitro...
Svahn, Malene F; Faber, Mette Tuxen; Christensen, Jane
The role of human papillomavirus (HPV) in the pathogenesis of ovarian cancer is controversial, and conflicting results have been published. We conducted a systematic review and meta-analysis to estimate the prevalence of HPV in epithelial ovarian cancer tissue.......The role of human papillomavirus (HPV) in the pathogenesis of ovarian cancer is controversial, and conflicting results have been published. We conducted a systematic review and meta-analysis to estimate the prevalence of HPV in epithelial ovarian cancer tissue....
Iwasaki, Ricardo; Galvez-Philpott, Felipe; Arias-Stella Jr.,Javier; Arias-Stella, Javier
Background: Molecular tests allow the detection of high-risk human papillomavirus in cervical samples, playing an important role in the prevention of cervical cancer. Objectives: We performed a study to determine the prevalence of HPV 16, HPV 18 and other high-risk human papillomavirus (pool 12 genotypes) in Peruvian females from diverse urban areas using the cobas 4800 HPV test. Methods: Routine cervical samples collected in our laboratory were analyzed by cobas 4800 HPV test. Results:...
Sjö, Nicolai Christian
ophthalmology, lacrimal sac, tear sac, papilloma, carcinoma, papillomavirus, HPV, polymerase chain reaction, PCR, RNA, DNA, in situ hybridisation, aetiology, conjunctiva, dysplasia, sex, age, distribution......ophthalmology, lacrimal sac, tear sac, papilloma, carcinoma, papillomavirus, HPV, polymerase chain reaction, PCR, RNA, DNA, in situ hybridisation, aetiology, conjunctiva, dysplasia, sex, age, distribution...
Background Human papillomavirus (HPV) is associated with different malignancies but its role in the pathogenesis of ovarian cancer is controversial. This study investigated the prevalence, genotyping and physical state of HPV in ovarian cancer Saudi patients. Methods Hundred formalin fixed paraffin embedded (FFPE) ovarian carcinoma tissues and their normal adjacent tissues (NAT) were included in the study. HPV was detected by nested polymerase chain reaction (PCR) using degenerated HPVL1 consensus primer pairs MY09/MY11 and GP5+/GP6 + to amplify a broad spectrum of HPV genotypes in a single reaction. The HPV positive samples were further genotyped using DNA sequencing. The physical state of the virus was identified using Amplification of Papillomavirus Oncogene Transcripts (APOT) assay in the samples positive for HPV16 and/or HPV18. Results High percentage of HPV (42%) was observed in ovarian carcinoma compared to 8% in the NAT. The high-risk HPV types 16, 18 and 45 were highly associated with the advanced stages of tumor, while low-risk types 6 and 11 were present in NAT. In malignant tissues, HPV-16 was the most predominant genotype followed by HPV-18 and -45. The percentage of viral integration into the host genome was significantly high (61.1%) compared to 38.9% episomal in HPV positive tumors tissues. In HPV18 genotype the percentage of viral integration was 54.5% compared to 45.5% episomal. Conclusion The high risk HPV genotypes in ovarian cancer may indicate its role in ovarian carcinogenesis. The HPV vaccination is highly recommended to reduce this type of cancer. PMID:24252426
Schellenbacher, Christina; Roden, Richard B S; Kirnbauer, Reinhard
Infections with sexually transmitted high-risk Human Papillomavirus (hrHPV), of which there are at least 15 genotypes, are responsible for a tremendous disease burden by causing cervical, and subsets of other ano-genital and oro-pharyngeal carcinomas, together representing 5% of all cancer cases worldwide. HPV subunit vaccines consisting of virus-like particles (VLP) self-assembled from major capsid protein L1 plus adjuvant have been licensed. Prophylactic vaccinations with the 2-valent (HPV16/18), 4-valent (HPV6/11/16/18), or 9-valent (HPV6/11/16/18/31/33/45/52/58) vaccine induce high-titer neutralizing antibodies restricted to the vaccine types that cause up to 90% of cervical carcinomas, a subset of other ano-genital and oro-pharyngeal cancers and 90% of benign ano-genital warts (condylomata). The complexity of manufacturing multivalent L1-VLP vaccines limits the number of included VLP types and thus the vaccines' spectrum of protection, leaving a panel of oncogenic mucosal HPV unaddressed. In addition, current vaccines do not protect against cutaneous HPV types causing benign skin warts, or against beta-papillomavirus (betaPV) types implicated in the development of non-melanoma skin cancer (NMSC) in immunosuppressed patients. In contrast with L1-VLP, the minor capsid protein L2 contains type-common epitopes that induce low-titer yet broadly cross-neutralizing antibodies to heterologous PV types and provide cross-protection in animal challenge models. Efforts to increase the low immunogenicity of L2 (poly)-peptides and thereby to develop broader-spectrum HPV vaccines are the focus of this review. Copyright © 2016 Elsevier B.V. All rights reserved.
Carlo Foresta; Cristina Patassini; Alessandro Bertoldo; Massimo Menegazzo; Felice Francavilla; Luisa Barzon; Alberto Ferlin
Human papillomaviruses (HPVs) are agents of the most common sexually transmitted diseases in females and males. Precise data about the presence, mechanism of infection and clinical significance of HPV in the male reproductive tract and especially in sperm are not available. Here we show that HPV can infect human sperm, it localizes at the equatorial region of sperm head through interaction between the HPV capsid protein L1 and syndecan-1. Sperm transfected with HPV E6/E7 genes and sperm expos...
Grasso, Felicia; Negri, Donatella R M; Mochi, Stefania; Rossi, Alessandra; Cesolini, Armando; Giovannelli, Andrea; Chiantore, Maria Vincenza; Leone, Pasqualina; Giorgi, Colomba; Cara, Andrea
Persistent infection with high risk genotypes of human papillomavirus (HPV) is the cause of cervical cancer, one of most common cancer among woman worldwide, and represents an important risk factor associated with other anogenital and oropharyngeal cancers in men and women. Here, we designed a therapeutic vaccine based on integrase defective lentiviral vector (IDLV) to deliver a mutated nononcogenic form of HPV16 E7 protein, considered as a tumor specific antigen for immunotherapy of HPV-associated cervical cancer, fused to calreticulin (CRT), a protein able to enhance major histocompatibility complex class I antigen presentation (IDLV-CRT/E7). Vaccination with IDLV-CRT/E7 induced a potent and persistent E7-specific T cell response up to 1 year after a single immunization. Importantly, a single immunization with IDLV-CRT/E7 was able to prevent growth of E7-expressing TC-1 tumor cells and to eradicate established tumors in mice. The strong therapeutic effect induced by the IDLV-based vaccine in this preclinical model suggests that this strategy may be further exploited as a safe and attractive anticancer immunotherapeutic vaccine in humans. Copyright © 2012 UICC.
Everton Faccini Augusto; Larissa Silva dos Santos; Ledy do Horto dos Santos Oliveira
OBJECTIVES: to survey the prevalence of human papillomavirus, associated risk factors and genotype distribution in women who were referred to cervical cancer screening when attended in a Family Health Program. METHOD: we conducted a cross-sectional survey, investigating 351 women. Polymerase chain reaction for DNA amplification and restriction fragment length polymorphism analysis were used to detect and typify the papillomavirus. RESULTS: virus infection was detected in 8.8% of the ...
Nghi, Nguyen Quy; Lamontagne, D Scott; Bingham, Allison; Rafiq, Mirriam; Mai, Le Thi Phuong; Lien, Nguyen Thi Phuong; Khanh, Nguyen Cong; Hong, Duong Thi; Huyen, Dang Thi Thanh; Tho, Nguyen Thi Thi; Hien, Nguyen Tran
Formative research is a useful tool for designing new health interventions. This paper presents key findings from formative research conducted in Vietnam to guide human papillomavirus (HPV) vaccine introduction. We explored the sociocultural environment, health system capacity and the policy-making process using a combined quantitative and qualitative methodology. Data collection was done through literature review, in-depth interviews, focus group discussions, observation checklists and a structured questionnaire on knowledge, attitudes and practices. Populations of interest included 11- to 14-year-old girls, their parents, community leaders, teachers, health workers, health and education officials, and policy-makers at all levels. Although HPV vaccines are new, we found high potential acceptance among parents and girls. HPV vaccine introduction was also favourably supported by health professionals if assurances for system preparedness, e.g. cold chain and human resources, were made. There were no significant barriers from the policy perspective that would prevent the introduction of a new vaccine. However, several concerns related to this new vaccine would need to be adequately addressed before implementation. Our findings provide options for potential vaccine delivery strategies, appropriate communication strategies and targeted advocacy strategies to introduce HPV vaccines in the Vietnamese context.
Korucuoglu, U; Guler, I; Dogan, H; Biri, A
Although the association of human papillomavirus (HPV) with warts arising in different parts of the human body has been well-demonstrated, the association of HPV with endometrial polyps has never been studied in the literature up to now. Detection of the HPV DNA was carried out by using 13 high-risk HPV real-time PCR Kit and five low-risk HPV real-time PCR Kit. Among 50 endometrial polyp samples, one endometrial polyp sample revealed a positive result for the presence of HPV type 18. This first study in the medical literature investigating the possible effect of HPV on the development of endometrial polyps has demonstrated that HPV might have a role in the development of some of the endometrial polyps. If the present authors' hypothesis that endometrial polyps caused by carcinogenic HPV types are prone to proceed to endometrial cancer if left untreated is correct, HPV vaccine has a potential to prevent development of at least some of the endometrial polyps and endometrial cancers.
Golde, R.J.T. van; Hullu, J.A. de; Bekkers, R.L.M.; Bulten, J.; Grefte, J.M.
Human papillomavirus (HPV) infection is an important factor in cervical carcinogenesis. We describe 3 cases of patients with difficulties in diagnosing either a primary or recurrent cervical carcinoma. These cases illustrate that detection of integrated HPV is helpful in diagnosing cervical
Magaldi, Thomas G.; Almstead, Laura L.; Bellone, Stefania; Prevatt, Edward G.; Santin, Alessandro D.; DiMaio, Daniel
Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repre...
Steinberg, B.M.; Brandsma, J.L. (Long Island Jewish Medical Center, NY (US)); Taichman, L.B. (State Univ. of New York, Stony Brook, NY (US))
This book contains over 30 selections. Some of the titles are: Elements that Control the Transcription of Genital Human Papillomavirus Type 18; Human Paillomavirus Gene Expression; RNA Probes to Analyze Human Papillomavirus Gene Expression in Squamous Papilloma of the Respiratory Tract; Expression of Human Papillomavirus Type-1 E4 Gene Products in Warts; and Underreplication of Human Papillomavirus Type-1 DNA in Cultures of Foreskin Keratinocytes.
Full Text Available There is considerable data to support a central role for human papillomavirus (HPV in the etiology of cervical cancer. More than a 100 HPV types have been described, and 40 have been isolated from benign and malignant genital lesions. Consequently, there is strong motivation to evaluate HPV testing for cervical cancer screening. Few studies concerning the natural history of HPV infection have been conducted in the state of Rio de Janeiro. We determined the prevalence of HPV types in female genital lesions by using Hybrid Capture Assay (HCA and we retrospectively analyzed the course of HPV infection. Our sample included 788 women attended at Laboratórios Sérgio Franco. The average age of the participants was 29.6 years. HPV prevalence and cytological diagnosis were determined. The overall prevalence of HPV DNA in the study group was 50.1% (395/788, ranging from 25% (NORMAL to 100% in high-grade intraepithelial lesions (HSIL. High risk HPV was found in 12% inflammatory, 58.3% HPV, 63.2% LSIL and 100% HSIL. A retrospective analysis of 78 patients showed that 22 presented persistent lesions, 2 had progressive lesions, 4 had regressive lesions, 13 showed latent infections, 18 were transiently infected and 19 were submitted to curative treatment. No cases of cancer were registered in this population, which can afford private medical care and regular follow-up exams. We suggest that HCA be used in specific cases involving persistent and recurrent lesions.
Full Text Available The human papillomavirus (HPV is a sexually transmitted infection common among men and women across all geographic and socioeconomic subgroups worldwide. Recent evidence suggests that HPV infection may affect fertility and alter the efficacy of assisted reproductive technologies. In men, HPV infection can affect sperm parameters, specifically motility. HPV-infected sperm can transmit viral DNA to oocytes, which may be expressed in the developing blastocyst. HPV can increase trophoblastic apoptosis and reduce the endometrial implantation of trophoblastic cells, thus increasing the theoretical risk of miscarriage. Vertical transmission of HPV during pregnancy may be involved in the pathophysiology of preterm rupture of membranes and spontaneous preterm birth. In patients undergoing intrauterine insemination for idiopathic infertility, HPV infection confers a lower pregnancy rate. In contrast, the evidence regarding any detrimental impact of HPV infection on IVF outcomes is inconclusive. It has been suggested that vaccination could potentially counter HPV-related sperm impairment, trophoblastic apoptosis, and spontaneous miscarriages; however, these conclusions are based on in vitro studies rather than large-scale epidemiological studies. Improvement in the understanding of HPV sperm infection mechanisms and HPV transmission into the oocyte and developing blastocyst may help explain idiopathic causes of infertility and miscarriage.
Full Text Available Following attachment to primary receptor heparan sulfate proteoglycans (HSPG, human papillomavirus type 16 (HPV16 particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.
Saslow, Debbie; Andrews, Kimberly S; Manassaram-Baptiste, Deana; Loomer, Lacey; Lam, Kristina E; Fisher-Borne, Marcie; Smith, Robert A; Fontham, Elizabeth T H
Answer questions and earn CME/CNE The American Cancer Society (ACS) reviewed and updated its guideline on human papillomavirus (HPV) vaccination based on a methodologic and content review of the Advisory Committee on Immunization Practices (ACIP) HPV vaccination recommendations. A literature review was performed to supplement the evidence considered by the ACIP and to address new vaccine formulations and recommendations as well as new data on population outcomes since publication of the 2007 ACS guideline. The ACS Guideline Development Group determined that the evidence supports ACS endorsement of the ACIP recommendations, with one qualifying statement related to late vaccination. The ACS recommends vaccination of all children at ages 11 and 12 years to protect against HPV infections that lead to several cancers and precancers. Late vaccination for those not vaccinated at the recommended ages should be completed as soon as possible, and individuals should be informed that vaccination may not be effective at older ages. CA Cancer J Clin 2016;66:375-385. © 2016 American Cancer Society. © 2016 American Cancer Society.
Full Text Available The role of human papillomavirus (HPV in prostate carcinogenesis is highly controversial: some studies suggest a positive association between HPV infection and an increased risk of prostate cancer (PCa, whereas others do not reveal any correlation. In this study, we investigated the prognostic impact of HPV infection on survival in 150 primary PCa patients. One hundred twelve (74.67% patients had positive expression of HPV E7 protein, which was evaluated in tumour tissue by immunohistochemistry. DNA analysis on a subset of cases confirmed HPV infection and revealed the presence of genotype 16. In Kaplan-Meier analysis, HPV-positive cancer patients showed worse overall survival (OS (median 4.59 years compared to HPV-negative (median 8.24 years, P=0.0381. In multivariate analysis age (P<0.001, Gleason score (P<0.001, nuclear grading (P=0.002, and HPV status (P=0.034 were independent prognostic factors for OS. In our cohort, we observed high prevalence of HPV nuclear E7 oncoprotein and an association between HPV infection and PCa survival. In the debate about the oncogenic activity of HPV in PCa, our results further confirm the need for additional studies to clarify the possible role of HPV in prostate carcinogenesis.
Corbitt, G; Zarod, A P; Arrand, J R; Longson, M; Farrington, W T
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
Li, Juan; Zhang, Tian-Yu; Tan, Le-Tian; Wang, Shu-Yi; Chen, Yu-Ying; Tian, Jie-Yan; Da, Wen-Ying; He, Ping; Zhao, Ya-Ming
The aim of this study was to evaluate the correlation between clinical behavior and expression of human papillomavirus (HPV) in patients with juvenile laryngeal papillomatosis, in an attempt to develop an effective molecular biological method to predict prognosis. We included 37 patients with juvenile laryngeal papillomatosis in the study group and 10 cases each of juvenile vocal cord polyps and juvenile normal laryngeal mucosa as the control group. We detected HPV by immunocytochemistry and in situ hybridization, identified the virus type, and measured HPV-DNA content using a computer-assisted, color pathological image-analysis system. Additionally, we conducted a retrospective study with regard to the patients' clinical history to evaluate the prognosis. The data of the 2 groups were compared and statistically analyzed, including a correlation with prognosis. In the study group, 67.3% (25/37) were positive for HPV-Ag by immunocytochemistry; whereas 53.2%, 45.8%, and 25.4% were positive for HPV6b-DNA, HPV11-DNA, and HPV6b+11-DNA, respectively, by in situ hybridization. HPV was not detected in the control group. There was a significant difference between two groups (P laryngeal papilloma (JLP) and that HPV6b-positivity can be used as an index to predict the development and outcome of JLP.
Chan, Paul K.S.; Picconi, María Alejandra; Cheung, Tak Hong; Giovannelli, Lucia; Park, Jong Sup
Human papillomavirus (HPV) infection is associated with a wide spectrum of disease that ranges from self-limited skin warts to life-threatening cancers. Since HPV plays a necessary etiological role in cervical cancer, it is logical to use HPV as a marker for early detection of cervical cancer and precancer. Recent advances in technology enable the development of high-throughput HPV assays of different formats, including DNA-based, mRNA-based, high-risk group-specific and type-specific methods. The ultimate goal of these assays is to improve the accuracy and cost-effiectiveness of cervical screening programs. HPV testing has several potential advantages compared to cytology-based screening. However, since the cancer to transient infection ratio is always low in the general population, HPV test results are bound to have a low positive predictive value that may subject women to unnecessary follow-up investigations. The wide-spread administration of prophylactic HPV vaccine will substantially decrease the incidence of cancer and precancer. This poses a number of challenges to cytology-based screening, and the role of HPV testing is expected to increase. Finally, apart from technical and cost-effiectiveness considerations, one should also keep in mind the psycho-social impact of using sexually-transmitted agents as a marker for cancer screening. PMID:22913405
Álvarez-Soria, M Josefa; Hernández-González, Amalia; Carrasco-García de León, Sira; del Real-Francia, M Ángeles; Gallardo-Alcañiz, M José; López-Gómez, José L
Primary prevention by prophylactic vaccination against the major cause of cervical cancer, the carcinogenic human papillomavirus (HPV) types 16 and 18, is now available worldwide. Postlicensure adverse neurological effects have been described. The studies realized after the license are descriptive and limited by the difficulty to obtain the information, despite most of the statistical indexes show that the adverse effects by the vaccine of the HPV are not upper compared with other vaccines, the substimation must be considered. We describe the cases of four young women that developed demyelinating disease after the vaccination of the HPV, with a rank of time between the administration of the dose and the development of the clinical of seven days to a month, with similar symptoms with the successive doses. We have described six episodes coinciding after the vaccination. Have been described seizures, autoimmune disorders such as Guillain-Barre syndrome, transverse myelitis, or motor neuron disease, probably adverse effects following immunization by HPV vaccine. So we suggest that vaccine may trigger an immunological mechanism leading to demyelinating events, perhaps in predisposed young.
Kano, Makoto; Kondo, Satoru; Wakisaka, Naohiro; Moriyama-Kita, Makiko; Nakanishi, Yosuke; Endo, Kazuhira; Murono, Shigeyuki; Nakamura, Hiroyuki; Yoshizaki, Tomokazu
Although Japan is a non-endemic area with nasopharyngeal carcinoma (NPC), the proportion of WHO type I NPC in Japan are different from that in non-endemic areas such as North America and Europe. Recently, it is said that not only Epstein-Barr virus (EBV) but also human papillomavirus (HPV) has an influence on NPC in non-endemic areas. The aim of this study is to clarify the influence of HPV on NPC in Japan. Paraffin-embedded tumor specimens were available for 59 patients with NPC diagnosed between 1996 and 2015. We detected the virus status by p16 immunohistochemistry, HPV PCR, and in situ hybridization for Epstein-Barr virus (EBV)-encoded RNA. Kaplan-Meier curves were used to compare the overall survival by viral status. Among the 59 patients, 49 (83%) were EBV-positive/HPV-negative, 2 (3%) were EBV-positive/HPV-positive, and 8 (16%) were EBV-negative/HPV-negative. All HPV-positive NPCs were co-infected with EBV. There were no significant differences between the overall survival in the three groups (p=0.111). In Japan, HPV was detected in a few patients with NPC, and we suggest that HPV has no influence on NPC carcinogenesis in this population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Ache, Kevin A; Wallace, Lorraine S
A large percentage of Internet users regularly search for health-related information. In recent years, participatory Internet sites such as YouTube have become increasingly popular, in part because individuals are able to both retrieve and post information. This study analyzed how human papillomavirus (HPV) vaccination was portrayed in videoclips and viewer-posted comments available on YouTube. YouTube (www.youtube.com) was queried on February 8, 2008, using the search terms Gardasil, cervical cancer vaccination, and HPV vaccination to identify and download relevant videoclips. Videoclips were classified as either positively or negatively portraying HPV vaccination, and viewer-posted comments were enumerated. Data analyses were conducted immediately following videoclip retrieval. A total of 146 unique YouTube videoclips were located, using the three search keywords combined. Three quarters (n=109; 74.7%) of the videoclips portrayed HPV vaccination in a positive manner. One third (n=47; 32.2%) of the videoclips had generated at least one posted comment. These results demonstrate that there is a wide variety of information on YouTube regarding HPV vaccination and cervical cancer. As a result, public health and medical professionals need to be cognizant of the nature of the HPV-related information available, so that they are better equipped to respond to patients who acquire information posted on YouTube and other Internet sources.
Liu, Su-Hsun; Rositch, Anne F; Viscidi, Raphael P; Silver, Michelle I; Burke, Anne E; Gravitt, Patti E
Obesity is known to increase susceptibility to certain infections in men. It is unclear whether obesity increases women's risk for human papillomavirus (HPV) infection. In a prospective cohort of 696 perimenopausal women enrolled in 2008-2012, we sought to determine whether obesity predicted incident HPV detection or nondetection. Obesity was defined as body mass index (BMI) ≥ 30 kg/m(2). Baseline any type HPV prevalence was comparable between obese and nonobese women (18.7% vs 19.1%; P > .05). Over a median follow-up period of 17.9 months (interquartile range: 12.1-24.5), 187 new HPV detections occurred among 123 women, 60 of whom subsequently lost 76 detectable infections. When compared with nonobese participants, obese women had a similar rate of new HPV detection (7.1 vs 7.8 infections per 1000 infection-years; P > .05) or loss of detection (100.3 vs 85.8 infections per 100 infection-years; P > .05). Similar results were found after adjusting for age, menopausal status, smoking habit, and sexual exposure history. Results from the current analysis suggest little effect of obesity on HPV detection and loss of detection in mid-adult women. More research is needed to determine whether adipokines or cytokines better capture the potential immune modulating effects of obesity on HPV infection.
Reis, Angela Adamski da Silva; Monteiro, Caroline Dias; Paula, Leonardo Barcelos de; Santos, Rodrigo da Silva; Saddi, Vera Aparecida; Cruz, Aparecido Divino da
The present study aimed to evaluate the applicability of an educational booklet that contained information for the general population about promotion and prevention of infections and neoplasic process caused by the human papillomavirus (HPV). The study was arranged in two phases. First, the booklet was given to 200 volunteers in the city of Goiânia, Goiás State. The applicability of the booklet was evaluated without the necessity of proving former knowledge. In the second phase, a detailed analysis of the data was made and the booklet revealed applicable. Then, the educational material was published and 2000 copies were distributed in a social event held by the Pontifícia Universidade Católica de Góias in the city of Goiânia. In the event, the booklet raised the interest of the general public and gave the volunteers a chance to participate in a study that investigated the presence of the HPV in the genital microbiote. The booklet proved to be applicable and reached its objective to inform and prevent. However, it's necessary to promote and improve campaigns to the population about the HPV and its relations with the neoplasic process.
Wright, Thomas C; Stoler, Mark H; Behrens, Catherine M; Apple, Raymond; Derion, Toniann; Wright, Teresa L
The objective of the study was to describe baseline data from Addressing the Need for Advanced HPV Diagnostics, a prospective, multicenter US cervical cancer screening trial. A total of 47,208 women aged 21 years or older undergoing routine screening were enrolled; liquid-based cytology and human papillomavirus (HPV) testing were performed. Women with abnormal cytology underwent colposcopy, as did high-risk HPV (hrHPV)-positive women and a random subset of women negative by both tests aged 25 years or older. Verification bias adjustment was applied; 95% confidence intervals were computed by the bootstrap method. The prevalence of cytologic abnormalities was 7.1%. hrHPV, HPV 16, and HPV 18 were detected using the cobas HPV Test in 12.6%, 2.8%, and 1.0% of women, respectively. Both cytologic abnormalities and hrHPV positivity declined with increasing age. The adjusted prevalence of cervical intraepithelial neoplasia grade 2 (CIN2) or greater in women aged 25-34 years was 2.3%, decreasing to 1.5% among older women. The Addressing the Need for Advanced HPV Diagnostics study provides important estimates of the prevalence of cytologic abnormalities, hrHPV positivity, and CIN2 or greater in a US screening population. Copyright © 2012 Mosby, Inc. All rights reserved.
Marlow, Laura A V; Wardle, Jane; Grant, Nina; Waller, Jo
With the introduction of human papillomavirus (HPV) testing and vaccination in the UK, health professionals will start to receive questions about the virus from their patients. This study aimed to identify the key questions about HPV that British women will ask when considering having an HPV test or vaccination. Face-to-face interviews were carried out with 21 women to discover what they wanted to know about HPV. A thematic framework approach was used to analyse the data and identify key themes in women's HPV knowledge requirements. Women's questions about HPV fell into six areas: identity (e.g. What are the symptoms?), cause (e.g. How do you get HPV?), timeline (e.g. How long does it last?), consequences (e.g. Does it always cause cervical cancer?) and control-cure (e.g. Can you prevent infection?). In addition, they asked procedural questions about testing and vaccination (e.g. Where do I get an HPV test?). These mapped well onto the dimensions identified in Leventhal's description of lay models of illness, called the 'Common Sense Model' (CSM). These results indicated that the majority of the questions women asked about HPV fitted well into the CSM, which therefore provides a structure for women's information needs. The findings could help health professionals understand what questions they may be expected to answer. Framing educational materials using the CSM themes may also help health educators achieve a good fit with what the public want to know.
Souho, Tiatou; Bennani, Bahia
Human papillomavirus (HPV) detection and genotyping are determinant in cervical cancer prevention. They help to identify women at risk and allow the establishment of epidemiologic profiles. Many PCR-based genotyping methods have been developed. They require many steps or specialized equipment increasing the assay duration and cost. This affects their routine use, especially in developing countries. Therefore, the aim of this study was to develop a new HPV genotyping method that can be routinely used also in low incomes countries. For this purpose, fifteen high risk HPV type specific reverse primers were designed on L1 gene and fluorescently labeled. These primers were used on two multiplex PCR with one common forward primer (MY11). The lengths of products were revealed by capillary electrophoresis. This technique identifies sixteen high risk HPVs (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 68, 73 and 82). It was optimized on HPV genome plasmids and evaluated on artificial and cervical samples. All the sixteen targeted genotypes were identified specifically and repeatedly in simple and multiple infections in both artificial and clinical samples. The developed technique is sensitive, specific, easy to perform and appropriate for routine laboratory use and high throughput screening programs. Copyright © 2013 Elsevier B.V. All rights reserved.
Caroline C. King
Full Text Available Objective. To evaluate associations between common vaginal infections and human papillomavirus (HPV. Study Design. Data from up to 15 visits on 756 HIV-infected women and 380 high-risk HIV-uninfected women enrolled in the HIV Epidemiology Research Study (HERS were evaluated for associations of bacterial vaginosis, trichomoniasis, and vaginal Candida colonization with prevalent HPV, incident HPV, and clearance of HPV in multivariate analysis. Results. Bacterial vaginosis (BV was associated with increased odds for prevalent (aOR = 1.14, 95% CI: 1.04, 1.26 and incident (aOR = 1.24, 95% CI: 1.04, 1.47 HPV and with delayed clearance of infection (aHR = 0.84, 95% CI: 0.72, 0.97. Whereas BV at the preceding or current visit was associated with incident HPV, in an alternate model for the outcome of incident BV, HPV at the current, but not preceding, visit was associated with incident BV. Conclusion. These findings underscore the importance of prevention and successful treatment of bacterial vaginosis.
Olatunbosun, O; Deneer, H; Pierson, R
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.
Pereira, Nigel; Kucharczyk, Katherine M; Estes, Jaclyn L; Gerber, Rachel S; Lekovich, Jovana P; Elias, Rony T; Spandorfer, Steven D
The human papillomavirus (HPV) is a sexually transmitted infection common among men and women across all geographic and socioeconomic subgroups worldwide. Recent evidence suggests that HPV infection may affect fertility and alter the efficacy of assisted reproductive technologies. In men, HPV infection can affect sperm parameters, specifically motility. HPV-infected sperm can transmit viral DNA to oocytes, which may be expressed in the developing blastocyst. HPV can increase trophoblastic apoptosis and reduce the endometrial implantation of trophoblastic cells, thus increasing the theoretical risk of miscarriage. Vertical transmission of HPV during pregnancy may be involved in the pathophysiology of preterm rupture of membranes and spontaneous preterm birth. In patients undergoing intrauterine insemination for idiopathic infertility, HPV infection confers a lower pregnancy rate. In contrast, the evidence regarding any detrimental impact of HPV infection on IVF outcomes is inconclusive. It has been suggested that vaccination could potentially counter HPV-related sperm impairment, trophoblastic apoptosis, and spontaneous miscarriages; however, these conclusions are based on in vitro studies rather than large-scale epidemiological studies. Improvement in the understanding of HPV sperm infection mechanisms and HPV transmission into the oocyte and developing blastocyst may help explain idiopathic causes of infertility and miscarriage.
Bohn, Olga-L; Navarro, Leticia; Saldivar, Jesus; Sanchez-Sosa, Sergio
To investigate the presence of human papillomavirus (HPV) in esophageal squamous papilloma (ESP) and determine p16, p53 and Ki67 expression in a Mexican cohort. Nineteen cases diagnosed as ESP, corresponding to 18 patients were reviewed; nineteen cases of normal esophageal mucosa were used as negative controls. HPV detection was performed by amplified chromogenic in situ hybridization (ACISH) using a wide spectrum-cocktail probe and PCR. The average age at presentation was 46.3 years (range 28-72 years). Patients included four (22.22%) males and 14 (77.77%) females. The most frequent location was upper third (11 cases), followed by middle third (3 cases) and unknown site (5 cases). Immunohistochemistry (IHC) revealed basal and focal p53 expression in 17 cases (89%); p16 was expressed in eight cases (42.10%) and the Ki67 index ranged from 10% to 30%. HPV was detected in 14 out of 16 cases (87.5%) by ACISH: Twelve showed diffuse nuclear patterns and two showed granular patterns. HPV DNA was identified by PCR in 12 out of 14 cases (85.7%). Low-risk HPV types were detected in the most of the cases. This study provides identification of HPV infection in almost 80% of ESP using either ACISH or PCR; overall, all of these lesions show low expression of cell-cycle markers. We suggest ACISH as an alternative diagnostic tool for HPV detection in ESP.
Gu, Can; Niccolai, Linda M; Yang, Shengbo; Wang, Xiuhua; Tao, Lijian
To examine young women's perceptions and acceptability of human papillomavirus vaccination and factors influencing acceptability in mainland China. In the light of current concepts, human papillomavirus vaccines serve as new paradigms in cervical cancer prevention programme for young women. However, knowledge and acceptability of human papillomavirus vaccination and factors influencing acceptability among young Chinese women are not known. We implemented a cross-sectional descriptive study in the Hunan province of China. One hundred and seventeen female undergraduate students completed confidential surveys in 2012. The questionnaire included five parts: background information, awareness and knowledge of human papillomavirus vaccine and cervical cancer, attitudes towards the vaccine and intentions to be vaccinated, psychosocial burden of human papillomavirus infection, and human papillomavirus-related sexual stigma. Only 44% of the participants were willing to be vaccinated in the future. Young women demonstrated low awareness and knowledge about human papillomavirus vaccine and cervical cancer. Their intention to receive future vaccination was associated with the high levels of knowledge about risk factors for cervical cancer and perceptions that infected women are responsible for their own infection of human papillomavirus. The results of this study suggest low awareness and knowledge among young Chinese women about the preventive nature and value of human papillomavirus vaccination. Social and cultural factors including moral obligation and STD-related stigma may influence young women's intention to future vaccination. Educational interventions are necessary to promote public awareness and deliver information about human papillomavirus vaccination and cervical cancer prevention. Results of this study can help health care practitioners develop appropriate programmes for the promotion of human papillomavirus vaccination among this population. © 2015 John Wiley
... Archive Data & Statistics Sexually Transmitted Diseases Figure 45. Human Papillomavirus — Prevalence of High-risk and Low-risk ... on the STD Data and Statistics page . * HPV = human papillomavirus. NOTE: Error bars indicate 95% confidence interval. ...
Ault, Kevin A; Joura, Elmar A; Kjaer, Susanne K
The primary objective of this report is to describe the detection of adenocarcinoma in situ (AIS) and associated human papillomavirus (HPV) type distribution that was observed in the context of two phase 3 clinical trials of a quadrivalent HPV6/11/16/18 vaccine. In this intention-to-treat analysis......, we include all women who had at least one follow-up visit postenrollment. Healthy women (17,622) aged 15-26 with no history of HPV disease and a lifetime number of less than five sex partners (average follow-up of 3.6 years) were randomized (1:1) to receive vaccine or placebo at day 1, months 2......, and 6. Women underwent colposcopy and biopsy according to a Papanicolaou triage algorithm. All tissue specimens were tested for 14 HPV types and were adjudicated by a pathology panel. During the trials, 22 women were diagnosed with AIS (six vaccine and 16 placebo). There were 25 AIS lesions in total...
Full Text Available Objective. To compare knowledge and attitudes of human papillomavirus (HPV and the vaccine between different cultures of African descent. Methods. A cross-sectional survey of 555 African-Americans and Afro-Caribbeans residing in the US and the Bahamas (BHM was conducted. Results. General knowledge about HPV and the HPV vaccine differed between the two countries significantly. Bahamian respondents were less likely to have higher numbers of correct knowledge answers when compared to Americans (Adjusted Odds Ratio [Adj. OR] 0.47, 95% Confidence Interval [CI] 0.30–0.75. Older age, regardless of location, was also associated with answering fewer questions correctly (Adj. OR 0.61, 95% CI 0.40–0.92. Attitudes related to HPV vaccination were similar between the US and BHM, but nearly 80% of BHM respondents felt that children should not be able to receive the vaccine without parental consent compared to 57% of American respondents. Conclusions. Grave lack of knowledge, safety and cost concerns, and influence of parental restrictions may negatively impact vaccine uptake among African-American and Afro-Caribbean persons. Interventions to increase the vaccine uptake in the Caribbean must include medical provider and parental involvement. Effective strategies for education and increasing vaccine uptake in BHM are crucial for decreasing cervical cancer burden in the Caribbean.
Binagwaho, Agnes; Wagner, Claire M; Gatera, Maurice; Karema, Corine; Nutt, Cameron T; Ngabo, Fidele
Virtually all women who have cervical cancer are infected with the human papillomavirus (HPV). Of the 275,000 women who die from cervical cancer every year, 88% live in developing countries. Two vaccines against the HPV have been approved. However, vaccine implementation in low-income countries tends to lag behind implementation in high-income countries by 15 to 20 years. In 2011, Rwanda's Ministry of Health partnered with Merck to offer the Gardasil HPV vaccine to all girls of appropriate age. The Ministry formed a "public-private community partnership" to ensure effective and equitable delivery. Thanks to a strong national focus on health systems strengthening, more than 90% of all Rwandan infants aged 12-23 months receive all basic immunizations recommended by the World Health Organization. In 2011, Rwanda's HPV vaccination programme achieved 93.23% coverage after the first three-dose course of vaccination among girls in grade six. This was made possible through school-based vaccination and community involvement in identifying girls absent from or not enrolled in school. A nationwide sensitization campaign preceded delivery of the first dose. Through a series of innovative partnerships, Rwanda reduced the historical two-decade gap in vaccine introduction between high- and low-income countries to just five years. High coverage rates were achieved due to a delivery strategy that built on Rwanda's strong vaccination system and human resources framework. Following the GAVI Alliance's decision to begin financing HPV vaccination, Rwanda's example should motivate other countries to explore universal HPV vaccine coverage, although implementation must be tailored to the local context.
Antonsson, Annika; Nancarrow, Derek J; Brown, Ian S; Green, Adele C; Drew, Paul A; Watson, David I; Hayward, Nicholas K; Whiteman, David C
Although most cases of esophageal squamous cell carcinoma (ESCC) in western populations have been attributed to high levels of exposure to tobacco and alcohol, infectious agents have been postulated as possible causes, particularly human papillomavirus (HPV). To explore this issue, we analyzed HPV DNA prevalence and HPV types together with lifestyle factors, in relation to tumor stage and survival in a low-incidence population. Archived tumor samples from a nationwide cohort of 222 ESCC patients were tested for the presence of HPV DNA by PCR; positive samples were sequenced to determine HPV type, and p16(INK4a) status was assessed by immunohistochemistry. Of 222 ESCC patients, 8 tested HPV positive (prevalence, 3.6%; 95% confidence interval, 1.1-6.1%), of which 6 were HPV-16 positive and 2 were HPV-35 positive. Four of the eight HPV-positive tumors overexpressed p16(INK4a). None of 55 normal esophageal tissue samples from healthy participants had any detectable HPV. Although the numbers were low, it seemed that patients with HPV-positive ESCC tumors were younger than those with HPV-negative tumors (mean age, 60.8 versus 65.3 years, P = 0.18) and had higher body mass index (BMI) throughout life (mean current BMI of 25.1 for HPV positive, 22.2 for HPV negative, P = 0.08; mean BMI at 20 years of 25.8 for HPV positive, 22.1 for HPV negative, P = 0.003). We found no difference between patients with HPV-positive and HPV-negative tumors with respect to other lifestyle factors. These findings suggest a very low prevalence of HPV DNA in human ESCC. HPV is very unlikely to be a common cause of ESCC in Australia. (c)2010 AACR.
Garolla, Andrea; Pizzol, Damiano; Foresta, Carlo
To review the role of human papillomavirus (HPV) on sperm parameters, fertility and implication of the use of infected sperm cells in assisted reproduction. HPVs are agents of the most common sexually transmitted disease and can lead to warts and cancers both in men and women.A high incidence of HPV infection has been demonstrated in sperm from sexually active men with and without risk factors for HPV and from infertile patients. Semen infection is associated to an impairment of sperm parameters suggesting a possible role in male infertility. Interestingly, it has been demonstrated that when HPV is present in semen only a percentage of total cells are infected and the virus can be localized in sperm or in exfoliated cells with different impact on sperm motility. Moreover, infected sperm are able to penetrate the oocyte, to deliver HPV genome in the oocyte and HPV genes can be actively transcribed by the fertilized oocyte. Recently an increased risk of pregnancy loss has been demonstrated in couples undergoing in-vitro fertilization and particularly when HPV DNA was present in semen samples of male partners. To date, no effective treatment, control strategy and prevention is provided for men despite the reported high incidence of HPV semen infection. Because this infection in men is also a problem for partners, and because growing evidence suggests that semen infection may cause infertility and early miscarriage, more attention should be paid to male HPV infection. This study reviews the more recent literature about the role of HPV infection on sperm function and human reproduction.
Comparison of two commercial assays for detection of human papillomavirus (HPV) in cervical scrape specimens: validation of the Roche AMPLICOR HPV test as a means to screen for HPV genotypes associated with a higher risk of cervical disorders.
Ham, M.A. van; Bakkers, J.M.J.E.; Harbers, G.; Quint, W.G.V.; Massuger, L.F.A.G.; Melchers, W.J.G.
Certain high-risk (HR) human papillomavirus (HPV) types are a necessary cause for the development of cervical disorders. Women with persistent HR HPV infections have an increased risk of developing high-grade cervical lesions, compared with those who have no or low-risk HPV infections. Therefore,
Ambühl, Lea M M; Leonhard, Anne K; Widen Zakhary, Carina; Jørgensen, Annemette; Blaakaer, Jan; Dybkaer, Karen; Baandrup, Ulrik; Uldbjerg, Niels; Sørensen, Suzette
Recently, an association between human papillomavirus infection and both spontaneous abortion and spontaneous preterm delivery was suggested. However, the reported human papillomavirus prevalence in pregnant women varies considerably and reliable conclusions are difficult. We aimed to investigate human papillomavirus infection in placental tissue of a Danish study cohort. Furthermore, we studied the cellular localization of human papillomavirus. In this prospective case-control study, placental tissue was analyzed for human papillomavirus infection by nested PCR in the following four study groups: full-term delivery (n = 103), spontaneous preterm delivery (n = 69), elective abortion (n = 54), and spontaneous abortion (n = 44). Moreover, human papillomavirus cellular target was identified using in situ hybridization. Human papillomavirus prevalence in placental tissue was 8.7% in full-term deliveries, 8.8% in spontaneous preterm deliveries, 10.9% in spontaneous abortions, and 20.4% in elective abortions. Twelve different human papillomavirus types were detected, and placental human papillomavirus infection was associated to a disease history of cervical cancer. Human papillomavirus DNA was identified in trophoblast cells, cells of the placental villi mesenchyme including Hofbauer cells, and in parts of the encasing endometrium. Placental human papillomavirus infections are not likely to constitute a risk factor for spontaneous preterm labor or spontaneous abortions in the Danish population, although an effect of human papillomavirus DNA in placental cells cannot be excluded. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.
Dilley, Sarah; Scarinci, Isabel; Kimberlin, David; Straughn, J Michael
Human papillomavirus-related cancers, which include cervical, vulvovaginal, anal, and oropharyngeal cancers, are on the rise in the United States. Although the human papillomavirus vaccine has been on the market for 10 years, human papillomavirus vaccination rates are well below national goals. Research identified many barriers and facilitators to human papillomavirus vaccination, and provider recommendation remains the most important factor in parental and patient decisions to vaccinate. While much of the burden of human papillomavirus vaccine provision falls on pediatricians and primary care providers, they cannot do it alone. As clinicians who care for a large proportion of human papillomavirus-related conditions, obstetrician-gynecologists and other women's health care providers must share the responsibility for vaccination of eligible patients. Obstetrician-gynecologists can support the efforts to eradicate human papillomavirus-related disease in their patients and their families via multiple avenues, including providing the human papillomavirus vaccine and being community leaders in support of vaccination. Copyright © 2017 Elsevier Inc. All rights reserved.
Dartell, Myassa Arkam; Rasch, Vibeke; Munk, Christian
Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. The prevalence is dependent on several known factors notably sexual behavior and age, and factors still under scrutiny.......Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. The prevalence is dependent on several known factors notably sexual behavior and age, and factors still under scrutiny....
Alemany, Laia; Cubilla, Antonio; Halec, Gordana; Kasamatsu, Elena; Quirós, Beatriz; Masferrer, Emili; Tous, Sara; Lloveras, Belén; Hernández-Suarez, Gustavo; Lonsdale, Ray; Tinoco, Leopoldo; Alejo, Maria; Alvarado-Cabrero, Isabel; Laco, Jan; Guimerà, Nuria; Poblet, Enrique; Lombardi, Luis E; Bergeron, Christine; Clavero, Omar; Shin, Hai-Rim; Ferrera, Annabelle; Felix, Ana; Germar, Julieta; Mandys, Vaclav; Clavel, Christine; Tzardi, Maria; Pons, Luis E; Wain, Vincent; Cruz, Eugenia; Molina, Carla; Mota, Jose D; Jach, Robert; Velasco, Julio; Carrilho, Carla; López-Revilla, Ruben; Goodman, Marc T; Quint, Wim G; Castellsagué, Xavier; Bravo, Ignacio; Pawlita, Michael; Muñoz, Nubia; Bosch, F Xavier; de Sanjosé, Silvia
Invasive penile cancer is a rare disease with an approximately 22 000 cases per year. The incidence is higher in less developed countries, where penile cancer can account for up to 10% of cancers among men in some parts of Africa, South America, and Asia. To describe the human papillomavirus (HPV) DNA prevalence, HPV type distribution, and detection of markers of viral activity (ie, E6*I mRNA and p16(INK4a)) in a series of invasive penile cancers and penile high-grade squamous intraepithelial lesions (HGSILs) from 25 countries. A total of 85 penile HGSILs and 1010 penile invasive cancers diagnosed from 1983 to 2011 were included. After histopathologic evaluation of formalin-fixed paraffin-embedded samples, HPV DNA detection and genotyping were performed using the SPF-10/DEIA/LiPA25 system, v.1 (Laboratory Biomedical Products, Rijswijk, The Netherlands). HPV DNA-positive cases were additionally tested for oncogene E6*I mRNA and all cases for p16(INK4a) expression, a surrogate marker of oncogenic HPV activity. HPV DNA prevalence and type distributions were estimated. HPV DNA was detected in 33.1% of penile cancers (95% confidence interval [CI], 30.2-36.1) and in 87.1% of HGSILs (95% CI, 78.0-93.4). The warty-basaloid histologic subtype showed the highest HPV DNA prevalence. Among cancers, statistically significant differences in prevalence were observed only by geographic region and not by period or by age at diagnosis. HPV16 was the most frequent HPV type detected in both HPV-positive cancers (68.7%) and HGSILs (79.6%). HPV6 was the second most common type in invasive cancers (3.7%). The p16(INK4a) upregulation and mRNA detection in addition to HPV DNA positivity were observed in 69.3% of HGSILs, and at least one of these HPV activity markers was detected in 85.3% of cases. In penile cancers, these figures were 22.0% and 27.1%, respectively. About a third to a fourth of penile cancers were related to HPV when considering HPV DNA detection alone or adding an HPV
Approximately 2 million new cancer cases are attributed to infectious agents each year worldwide. Vaccines for the hepatitis B virus (HBV), a risk factor of hepatocellular cancer, and human papillomavirus (HPV), a risk factor of cervical cancer, are considered major successes in clinical chemoprevention of cancer. In Taiwan, the first evidence of cancer prevention through vaccinations was provided by HBV vaccination data in infants. The Taiwanese HBV vaccination program has since become a model immunization schedule for newborns worldwide. Persistent infection with high-risk HPV is generally accepted as prerequisite for cervical cancer diagnosis; however, cervical cancer is a rare complication of HPV infections. This is due to the fact that such infections tend to be transient. The safety and efficacy of both available HPV quadrivalent vaccine and bivalent vaccine are not in doubt at the present time. Until a human cytomegalovirus (CMV) vaccine becomes available, simple hygienic practices, such as hand washing, can prevent CMV infection both before and during pregnancy. Each country should establish her official guidelines regarding which vaccines should be used to treat various conditions, the target population (i.e., universal or limited to a selected population), and the immunization schedules. After a vaccine is recommended, decisions regarding reimbursement by the public health care fund are evaluated. The guidelines become part of the immunization schedule, which is updated annually and published in the official bulletin. In conclusion, both HBV and HPV vaccines are considered major successes in the chemoprevention of cancer. Copyright © 2015. Published by Elsevier B.V.
Full Text Available Persistent infection of basal keratinocytes with high-risk human papillomavirus (hrHPV may cause cancer. Keratinocytes are equipped with different pattern recognition receptors (PRRs but hrHPV has developed ways to dampen their signals resulting in minimal inflammation and evasion of host immunity for sustained periods of time. To understand the mechanisms underlying hrHPV's capacity to evade immunity, we studied PRR signaling in non, newly, and persistently hrHPV-infected keratinocytes. We found that active infection with hrHPV hampered the relay of signals downstream of the PRRs to the nucleus, thereby affecting the production of type-I interferon and pro-inflammatory cytokines and chemokines. This suppression was shown to depend on hrHPV-induced expression of the cellular protein ubiquitin carboxyl-terminal hydrolase L1 (UCHL1 in keratinocytes. UCHL1 accomplished this by inhibiting tumor necrosis factor receptor-associated factor 3 (TRAF3 K63 poly-ubiquitination which lead to lower levels of TRAF3 bound to TANK-binding kinase 1 and a reduced phosphorylation of interferon regulatory factor 3. Furthermore, UCHL1 mediated the degradation of the NF-kappa-B essential modulator with as result the suppression of p65 phosphorylation and canonical NF-κB signaling. We conclude that hrHPV exploits the cellular protein UCHL1 to evade host innate immunity by suppressing PRR-induced keratinocyte-mediated production of interferons, cytokines and chemokines, which normally results in the attraction and activation of an adaptive immune response. This identifies UCHL1 as a negative regulator of PRR-induced immune responses and consequently its virus-increased expression as a strategy for hrHPV to persist.
Reinson, Tormi; Henno, Liisi; Toots, Mart; Ustav, Mart; Ustav, Mart
Viruses manipulate the cell cycle of the host cell to optimize conditions for more efficient viral genome replication. One strategy utilized by DNA viruses is to replicate their genomes non-concurrently with the host genome; in this case, the viral genome is amplified outside S phase. This phenomenon has also been described for human papillomavirus (HPV) vegetative genome replication, which occurs in G2-arrested cells; however, the precise timing of viral DNA replication during initial and stable replication phases has not been studied. We developed a new method to quantitate newly synthesized DNA levels and used this method in combination with cell cycle synchronization to show that viral DNA replication is initiated during S phase and is extended to G2 during initial amplification but follows the replication pattern of cellular DNA during S phase in the stable maintenance phase. E1 and E2 protein overexpression changes the replication time from S only to both the S and G2 phases in cells that stably maintain viral episomes. These data demonstrate that the active synthesis and replication of the HPV genome are extended into the G2 phase to amplify its copy number and the duration of HPV genome replication is controlled by the level of the viral replication proteins E1 and E2. Using the G2 phase for genome amplification may be an important adaptation that allows exploitation of changing cellular conditions during cell cycle progression. We also describe a new method to quantify newly synthesized viral DNA levels and discuss its benefits for HPV research.
Shakya, Sunila; Syversen, Unni; Åsvold, Bjørn O; Bofin, Anna M; Aune, Guro; Nordbø, Svein A; Vaidya, Karishma M; Karmacharya, Biraj M; Afset, Jan E; Tingulstad, Solveig
In this study we aimed to determine the overall and type-specific prevalence of cervical human papillomavirus (HPV) infection and risk factors for such infection among women in rural Nepal, and to investigate the distribution of HPV infection by cervical cytology. The study was conducted among women aged ≥15 years in five rural villages within Kavre District in Nepal. Sociodemographic data and information on risk factors for cervical cancer were obtained through an interview, and a cervical specimen was collected for HPV DNA detection and typing using the Anyplex™ ll HPV28 Detection system, and for Papanicolaou test. Among the 1289 women in whom a valid HPV result was obtained the median age was 40 years (range 17-86 years). Overall, the HPV prevalence was 14.4%, 7.9% for high-risk and 6.5% for low-risk HPV types, and was similar between age groups. The five most common HR types were HPV-18 (2.3%), HPV-51 (1.2%), HPV-59 (1.1%), HPV-31 (0.9%), and HPV-16 (0.8%). The prevalence of high-risk types in women with and without abnormal cytology was 8.3 and 7.7%, respectively. HPV infection was associated with current smoking, formal education, and being married to a husband with at least one previous marriage. This is the first population-based study to report the prevalence of a broad range of HPV types among women from rural Nepal. These data are crucial for development of preventive strategies to reduce cervical cancer burden in the country. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.
Navarro-Illana, P; Caballero, P; Tuells, J; Puig-Barberá, J; Diez-Domingo, J
In October 2008, Valencian Community started its human papillomavirus (HPV) vaccination schedules for 14 year-old girls. The aim of this study is to assess knowledge about HPV infection and its vaccine among the mothers of these girls, and to identify factors associated with the willingness to vaccinate their daughters. Cross-sectional study by means of a questionnaire to mothers of girls born in 1995, and attending secondary schools in the province of Valencia during 2010-2011. Cluster stratified random sample (n=1279). percentages, confidence intervals, OR, Chi-squared and multivariate logistic regression contrasts. A total of 833 (65.1%) questionnaires were completed. The results obtained showed that, 76.6% of mothers had vaccinated their daughters against HPV; 93.8% knew about the vaccine, particularly through television (71.5%); and 78.5% received positive advice from a health professional which increased the vaccination of their daughters (OR: 2.4). There was low overall knowledge about HPV infection and vaccination. Confidence of the mothers in vaccines as a preventative method increases the HPV vaccination (OR: 3.8). The first reason for refusal was the fear of adverse events (45.6%). Apparently, the media does not influence the willingness to vaccinate. It would be desirable to minimize the perception of risk of the vaccine. Positive health advice from a health professional can have a positive effect on vaccination. There is a gap between the level of knowledge and decision-making to vaccinate. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.
Lewis-Bell, Karen; Luciani, Silvana; Unger, Elizabeth R; Hariri, Susan; McFarlane, Shelly; Steinau, Martin; Prieto-Lara, Elisa; Vicari, Andrea S; Irons, Beryl; Lewis, Merle J; Andrus, Jon Kim
To characterize the prevalence and distribution of genital human papillomavirus (HPV) types among women in Jamaica, and to explore risk factors associated with HPV infection. This was a cross-sectional study that took place in April-July 2010 with 852 sexually-active women, 16-49 years of age, who had attended a selected public or private primary health clinic in one of Jamaica's four health authority regions. Sociodemographic data was collected from each participant by trained study staff. Each participant had a gynecological examination that included a clinical Pap test and a cervical sample for HPV detection and typing-performed using the Research Use Only Linear Array (LA) genotyping assay (Roche Diagnostics Corp., Indianapolis, Indiana, United States). Overall and type-specific prevalence of HPV infection was calculated for 37 HPV types included in the LA genotyping assay. HPV DNA was detected in 460 of the 852 women (54.0%). Oncogenic HPV was detected in 297 women (34.9%) and HPV types 16/18 were found in 86 women (10.1%). The most frequently occurring HPV types were: 16 (6.2%); 35 (6.0%); 62 and 83 (5.5%); 61 and 58 (5.4%); 84 (4.7%); 18 (4.3%); and, 66 and 81 (4.2%). HPV prevalence was highest among women who were single, young (16-19 years), and had had more than three sexual partners in their lifetime. These results, coupled with high rates of cervical cancer, support introducing HPV vaccines while maintaining and strengthening cervical cancer screening services. Policy decision-making that reflects these results is instrumental to establishing a comprehensive cervical cancer program in Jamaica.
Brestovac, Brian; Wong, Michelle E; Costantino, Paul S; Groth, David
Infection with oncogenic human papillomavirus (HPV) genotypes is necessary for the development of cervical cancer. Testing for HPV DNA from liquid based cervical samples can be used as an adjunct to traditional cytological screening. In addition there are ongoing viral load, genotyping, and prevalence studies. Therefore, a sensitive DNA extraction method is needed to maximize the efficiency of HPV DNA detection. The XytXtract Tissue kit is a DNA extraction kit that is rapid and so could be useful for HPV testing, particularly in screening protocols. This study was undertaken to determine the suitability of this method for HPV detection. DNA extraction from HeLa and Caski cell lines containing HPV 18 and 16 respectively together with DNA from five liquid based cervical samples were used in a HPV PCR assay. DNA was also extracted using the QIAamp DNA mini kit (Qiagen, Hilden, Germany) as a comparison. DNA extracts were serially diluted and assayed. HPV DNA was successfully detected in cell lines and cervical samples using the XytXtract Tissue kit. In addition, the XytXtract method was found to be more sensitive than the QIAmp method as determined by a dilution series of the extracted DNA. While the XytXtract method is a closed, the QIAamp method uses a spin column with possible loss of DNA through DNA binding competition of the matrix, which could impact on the final extraction efficiency. The XytXtract is a cheap, rapid and efficient method for extracting HPV DNA from both cell lines and liquid based cervical samples. © 2014 Wiley Periodicals, Inc.
Nelson, Erik J; Hughes, John; Oakes, J Michael; Pankow, James S; Kulasingam, Shalini L
To identify factors associated with human papillomavirus (HPV) vaccination and to determine the geographic distribution of vaccine uptake while accounting for spatial autocorrelation. This study is cross-sectional in design using data collected via the Internet from the Survey of Minnesotans About Screening and HPV study. The sample consists of 760 individuals aged 18-30 years nested within 99 ZIP codes surrounding the downtown area of Minneapolis, Minnesota. In all, 46.2% of participants had received ≥ 1 dose of HPV vaccine (67.7% of women and 13.0% of men). Prevalence of HPV vaccination was found to exhibit strong spatial dependence ([Formula: see text] = 0.9951) across ZIP codes. Accounting for spatial dependence, age (OR=0.76, 95% CI 0.70 to 0.83) and male gender (OR=0.04, 95% CI 0.03 to 0.07) were negatively associated with vaccination, while liberal political preferences (OR=4.31, 95% CI 2.32 to 8.01), and college education (OR=2.58, 95% CI 1.14 to 5.83) were found to be positively associated with HPV vaccination. Strong spatial dependence and heterogeneity of HPV vaccination prevalence were found across ZIP codes, indicating that spatial statistical models are needed to accurately identify and estimate factors associated with vaccine uptake across geographic units. This study also underscores the need for more detailed data collected at local levels (eg, ZIP code), as patterns of HPV vaccine receipt were found to differ significantly from aggregated state and national patterns. Future work is needed to further pinpoint areas with the greatest disparities in HPV vaccination and how to then access these populations to improve vaccine uptake. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Full Text Available In 2007, human papillomavirus (HPV type 16 was recognized as a risk factor by the International Agency for Research on Cancer, for oropharyngeal squamous cell carcinoma (OSCC, where tonsillar and base of tongue cancer (TSCC and BOTSCC dominate. Furthermore, patients with HPV-positive TSCC and BOTSCC, had a much better clinical outcome than those with corresponding HPV-negative cancer and other head and neck cancer. More specifically, survival was around 80% for HPV-positive TSCC and BOTSCC vs. 40% five-year disease free survival, for the corresponding HPV-negative tumors with conventional radiotherapy and surgery, while this could not be observed for HPV-positive OSCC at other sites. In addition, the past 20–40 years in many Western Countries, the incidence of HPV-positive TSCC and BOTSCC has risen, and >70% are men. This has resulted in a relative increase of patients with HPV-positive TSCC and BOTSCC that may not need the intensified chemo-radiotherapy (with many more severe debilitating side effects often given today to patients with head and neck cancer. However, before tapering therapy, one needs to enable selection of patients for such treatment, by identifying clinical and molecular markers that together with HPV-positive status will better predict patient prognosis and response to therapy. To conclude, there is a new increasing group of patients with HPV-positive TSCC and BOTSCC with good clinical outcome, where options for better-tailored therapy are needed. For prevention, it would be of benefit to vaccinate both girls and boys against HPV16 infection. For potential future screening the ways to do so need optimizing.
Pinatti, L M; Walline, H M; Carey, T E
We conducted a critical review of human papillomavirus (HPV) integration into the host genome in oral/oropharyngeal cancer, reviewed the literature for HPV-induced cancers, and obtained current data for HPV-related oral and oropharyngeal cancers. In addition, we performed studies to identify HPV integration sites and the relationship of integration to viral-host fusion transcripts and whether integration is required for HPV-associated oncogenesis. Viral integration of HPV into the host genome is not required for the viral life cycle and might not be necessary for cellular transformation, yet HPV integration is frequently reported in cervical and head and neck cancer specimens. Studies of large numbers of early cervical lesions revealed frequent viral integration into gene-poor regions of the host genome with comparatively rare integration into cellular genes, suggesting that integration is a stochastic event and that site of integration may be largely a function of chance. However, more recent studies of head and neck squamous cell carcinomas (HNSCCs) suggest that integration may represent an additional oncogenic mechanism through direct effects on cancer-related gene expression and generation of hybrid viral-host fusion transcripts. In HNSCC cell lines as well as primary tumors, integration into cancer-related genes leading to gene disruption has been reported. The studies have shown that integration-induced altered gene expression may be associated with tumor recurrence. Evidence from several studies indicates that viral integration into genic regions is accompanied by local amplification, increased expression in some cases, interruption of gene expression, and likely additional oncogenic effects. Similarly, reported examples of viral integration near microRNAs suggest that altered expression of these regulatory molecules may also contribute to oncogenesis. Future work is indicated to identify the mechanisms of these events on cancer cell behavior.
Comparison of the AdvanSure human papillomavirus screening real-time PCR, the Abbott RealTime High Risk human papillomavirus test, and the Hybrid Capture human papillomavirus DNA test for the detection of human papillomavirus.
Hwang, Yusun; Lee, Miae
We evaluated the performance of various commercial assays for the molecular detection of human papillomavirus (HPV); the recently developed AdvanSure HPV Screening real-time PCR assay (AdvanSure PCR) and the Abbott RealTime High Risk HPV PCR assay (Abbott PCR) were compared with the Hybrid Capture 2 HPV DNA Test (HC2). All 3 tests were performed on 177 samples, and any sample that showed a discrepancy in any of the 3 tests was genotyped using INNO-LiPA HPV genotyping and/or sequencing. On the basis of these results, we obtained a consensus HPV result, and the performance of each test was evaluated. We also evaluated high-risk HPV 16/18 detection by using the 2 real-time PCR assays. Among the 177 samples, 65 were negative and 75 were positive in all 3 assays; however, the results of the 3 assays with 37 samples were discrepant. Compared with the consensus HPV result, the sensitivities and specificities of HC2, AdvanSure PCR, and Abbott PCR were 97.6%, 91.7%, and 86.9% and 83.9%, 98.8%, and 100.0%, respectively. For HPV type 16/18 detection, the concordance rate between the AdvanSure PCR and Abbott PCR assays was 98.3%; however, 3 samples were discrepant (positive in AdvanSure PCR and negative in Abbott PCR) and were confirmed as HPV type 16 by INNO-LiPA genotyping and/or sequencing. For HPV detection, the AdvanSure HPV Screening real-time PCR assay and the Abbott PCR assay are less sensitive but more specific than the HC2 assay, but can simultaneously differentiate type 16/18 HPV from other types.
Full Text Available BACKGROUND: Current prophylactic vaccines against human papillomavirus (HPV target two oncogenic types (16 and 18 that contribute to 70% of cervical cancer cases worldwide. Our objective was to quantify the range of additional benefits conferred by second-generation HPV prophylactic vaccines that are expected to expand protection to five additional oncogenic types (31, 33, 45, 52 and 58. METHODS: A microsimulation model of HPV and cervical cancer calibrated to epidemiological data from two countries (Kenya and Uganda was used to estimate reductions in lifetime risk of cervical cancer from the second-generation HPV vaccines. We explored the independent and joint impact of uncertain factors (i.e., distribution of HPV types, co-infection with multiple HPV types, and unidentifiable HPV types in cancer and vaccine properties (i.e., cross-protection against non-targeted HPV types, compared against currently-available vaccines. RESULTS: Assuming complete uptake of the second-generation vaccine, reductions in lifetime cancer risk were 86.3% in Kenya and 91.8% in Uganda, representing an absolute increase in cervical cancer reduction of 26.1% in Kenya and 17.9% in Uganda, compared with complete uptake of current vaccines. The range of added benefits was 19.6% to 29.1% in Kenya and 14.0% to 19.5% in Uganda, depending on assumptions of cancers attributable to multiple HPV infections and unidentifiable HPV types. These effects were blunted in both countries when assuming vaccine cross-protection with both the current and second-generation vaccines. CONCLUSION: Second-generation HPV vaccines that protect against additional oncogenic HPV types have the potential to improve cervical cancer prevention. Co-infection with multiple HPV infections and unidentifiable HPV types can influence vaccine effectiveness, but the magnitude of effect may be moderated by vaccine cross-protective effects. These benefits must be weighed against the cost of the vaccines in future
Klosky, James L; Hudson, Melissa M; Chen, Yanjun; Connelly, James A; Wasilewski-Masker, Karen; Sun, Can-Lan; Francisco, Liton; Gustafson, Laura; Russell, Kathryn M; Sabbatini, Gina; Flynn, Jessica S; York, Jocelyn M; Giuliano, Anna R; Robison, Leslie L; Wong, F Lennie; Bhatia, Smita; Landier, Wendy
Purpose Cancer survivors are at high risk for human papillomavirus (HPV)-related morbidities; we estimated the prevalence of HPV vaccine initiation in cancer survivors versus the US population and examined predictors of noninitiation. Methods Participants included 982 cancer survivors (9 to 26 years of age; 1 to 5 years postcompletion of therapy); we assessed HPV vaccine initiation, sociodemographic and clinical characteristics, and vaccine-specific health beliefs; age-, sex-, and year-matched US population comparisons were from the National Immunization Survey-Teen and the National Health Interview Survey (2012-2015). Results The mean age at the time of the study was 16.3 ± 4.7 years; the mean time off therapy was 2.7 ± 1.2 years; participants were 55% male and 66% non-Hispanic white; 59% had leukemia/lymphoma. Vaccine initiation rates were significantly lower in cancer survivors versus the general population (23.8%; 95% CI, 20.6% to 27.0% v 40.5%; 95% CI, 40.2% to 40.7%; P P P young adult survivors and peers (ages 18 to 26 years) was comparably low (25.3%; 95% CI, 20.9% to 29.7% v 24.2%; 95% CI, 23.6% to 24.9%). Predictors of noninitiation included lack of provider recommendation (OR, 10.8; 95% CI, 6.5 to 18.0; P P P P P < .001; comparison, 13 to 17 years). Conclusion HPV vaccine initiation rates in cancer survivors are low. Lack of provider recommendation and barriers to vaccine receipt should be targeted in vaccine promotion efforts.
Velázquez-Márquez, Noé; Jaime Jiménez-Aranda, Lucio; Sánchez-Alonso, Patricia; Santos-López, Gerardo; Reyes-Leyva, Julio; Vallejo-Ruiz, Verónica
Cervical cancer is an important health problem in women living in developing countries. Infection with some genotypes of human papillomavirus (HPV) is the most important risk factor associated with cervical cancer. Little information exists about HPV genotype distribution in rural and suburban regions of Mexico. Thus, we determined the prevalence of HPV genotypes in women from Tlaxcala, one of the poorest states in central Mexico, and we evaluated age infection prevalence and risk factors associated with cervical neoplasm. A cross-sectional study was conducted in 236 women seeking gynecological care at the Mexican Institute for Social Security in Tlaxcala, Mexico. Cervical scrapings were diagnosed as normal, low-grade, and high-grade squamous intraepithelial lesions (LGSIL, HGSIL). Parallel samples were used to detect HPV genotypes by PCR assays using type-specific primers for HPV 6, 11, 16, 18, and 31. An epidemiological questionnaire was applied. Prevalence of HPV infection was 31.3%. From the infected samples, prevalence of HPV 16 was 45.9%; HPV 18, 31.1%; HPV 31, 16.2%; HPV 6, 10.8%; HPV 11, 6.7%. With regard to age, the highest HPV prevalence (43.5%) was found in the 18- to 24-year-old group and the lowest (19%) in the 45- to 54-year-old group. None of the risk factors showed association with cervical neoplasia grade. HPV 16 was the most common in cervical lesions. HPV was present in 22% of normal samples and, of these, 82.6% represented high-risk HPVs. Tlaxcala showed HPV prevalence comparable to that of the largest cities in Mexico, with higher prevalence for HPV 31.
Full Text Available Cervical cancer is an important health problem in women living in developing countries. Infection with some genotypes of human papillomavirus (HPV is the most important risk factor associated with cervical cancer. Little information exists about HPV genotype distribution in rural and suburban regions of Mexico. Thus, we determined the prevalence of HPV genotypes in women from Tlaxcala, one of the poorest states in central Mexico, and we evaluated age infection prevalence and risk factors associated with cervical neoplasm. A cross-sectional study was conducted in 236 women seeking gynecological care at the Mexican Institute for Social Security in Tlaxcala, Mexico. Cervical scrapings were diagnosed as normal, low-grade, and high-grade squamous intraepithelial lesions (LGSIL, HGSIL. Parallel samples were used to detect HPV genotypes by PCR assays using type-specific primers for HPV 6, 11, 16, 18, and 31. An epidemiological questionnaire was applied. Prevalence of HPV infection was 31.3%. From the infected samples, prevalence of HPV 16 was 45.9%; HPV 18, 31.1%; HPV 31, 16.2%; HPV 6, 10.8%; HPV 11, 6.7%. With regard to age, the highest HPV prevalence (43.5% was found in the 18- to 24-year-old group and the lowest (19% in the 45- to 54-year-old group. None of the risk factors showed association with cervical neoplasia grade. HPV 16 was the most common in cervical lesions. HPV was present in 22% of normal samples and, of these, 82.6% represented high-risk HPVs. Tlaxcala showed HPV prevalence comparable to that of the largest cities in Mexico, with higher prevalence for HPV 31.
Full Text Available Abstract Background Nasopharyngeal carcinoma (NPC is a malignant tumor which arises in surface epithelium of the posterior wall of the nasopharynx. There's is evidence that Epstein Barr virus (EBV is associated to NPC development. However, many epidemiologic studies point to a connection between viral infections by the human papillomavirus (HPV and NPC. Method Seventy Moroccan patients with NPC were screened for EBV and HPV. EBV detection was performed by PCR amplification of BZLF1 gene, encoding the ZEBRA (Z Epstein-Barr Virus Replication Activator protein, and HPV infection was screened by PCR amplification with subsequent typing by hybridization with specific oligonucleotides for HPV types 16, 18, 31, 33, 35, 45 and 59. Results The age distribution of our patients revealed a bimodal pattern. Sixty two cases (88.9% were classified as type 3 (undifferentiated carcinoma, 6 (8.6% as type 2 (non keratinizing NPC and only 2 (2.9% cases were classified as type 1 (keratinizing NPC. EBV was detected in all NPC tumors, whereas HPV DNA was revealed in 34% of cases (24/70. Molecular analysis showed that 20.8% (5/24 were infected with HPV31, and the remaining were infected with other oncogenic types (i.e., HPV59, 16, 18, 33, 35 and 45. In addition, statistical analysis showed that there's no association between sex or age and HPV infection (P > 0.1. Conclusion Our data indicated that EBV is commonly associated with NPC in Moroccan patients and show for the first time that NPC tumours from Moroccan patients harbour high risk HPV genotypes.
Carvalho Maria Odete O.
Full Text Available Human Papillomavirus (HPV infection is the main cause of cervical cancers and cervical intraepithelial neoplasias (CIN worldwide. Consequently, it would be useful to evaluate HPV testing to screen for cervical cancer. Recently developed, the second-generation Hybrid Capture (HCA II test is a non-radioactive, relatively rapid, liquid hybridization assay designed to detect 18 HPV types, divided into high and low-risk groups. We evaluated 1055 women for HPV infection with the HCA II test. Five hundred and ten (48.3% of these women had HPV infection; 60 (11.8% had low cancer-risk HPV DNA; 269 (52.7% had high-risk HPV types and 181 (35.5% had both groups. Hence, 450 women (88.2% in this HPV-infected group had at least one high risk HPV type, and were therefore considered to be at high risk for cancer. Among the group with Papanicolaou (Pap test results, the overall prevalence of HPV DNA was 58.4%. Significant differences in HPV infection of the cervix were detected between Pap I (normal smears and Pap IV (carcinomas (p<0.0001. Values of HPV viral load obtained for Pap I and SILs were significantly different, with an upward trend (p<0.0001, suggesting a positive correlation between high viral load values and risk of SIL. Because of the high costs of the HCA II test, its use for routine cervical mass screening cannot be recommended in poor countries. Nevertheless, it is a useful tool when combined with cytology, diagnosing high-risk infections in apparently normal tissues. Use of this technique could help reduce the risk of cancer.
Brossfield, J E; Chan, P J; Patton, W C; King, A
Sperm cells have been shown to take up exogenous DNA readily. The hypothesis was that sperm washing would remove exogenous viral DNA infecting sperm cells. The objective was to compare three types of sperm washing procedures for their capacity to remove exogenous human papillomavirus (HPV) DNA from infected sperm. Prewashed sperm were equally divided and sperm in one portion were exposed to L1 HPV DNA fragments for 30 min at 37 degrees C. Untreated washed sperm served as the control. After transfection, the sperm were washed by either centrifuge, two-layer Isolate colloid wash, or test-yolk buffer procedures. Sperm parameters were measured on a Hamilton Thorn HTM-C analyzer. Sperm DNA were extracted and polymerase chain reaction (PCR) was carried out targeting the L1 consensus gene of HPV and the designated sentinel gene, 17q21 spanning the D17S855 gene. Amplified products were analyzed in 2% agarose gel electrophoresis. PCR analyses detected the consensus L1 HPV gene in sperm after they were processed through either of the three procedures. Controls were negative for the L1 gene. Extracted DNA were verified by PCR amplification of 17q21 spanning the D17S855 gene. Transfected sperm had higher percentages of total motility and progression compared with the control. Centrifuged, washed, transfected sperm exhibited a greater curvilinear velocity and hyperactivation. The data showed that washing would not remove exogenous HPV DNA from sperm cells. The viral DNA was tenaciously bound to the sperm, suggesting an internalization into the sperm. The viral DNA also increased the motility of the sperm by affecting the velocity and progression of the sperm, which suggested either an increase in metabolism, an enhancement of the calcium-regulated motility mechanism, or an artifact of PCR reagents. More studies are needed to elucidate the mechanism of DNA stimulated sperm motility.
Frazer, Ian H
The family of human papillomaviruses (HPVs) includes more than 130 genotypes, many of which infect the genital tract, and these can be classified as low risk or high risk for induction of genital neoplasia. Two prophylactic vaccines are currently available for the prevention of genital HPV infection: a quadrivalent (Gardasil); Merck & Co. Inc) and a bivalent (Cervarix; GlaxoSmithKline) vaccine. Protection against HPV infection and associated disease is observed for at least 6.4 years following immunization with the bivalent vaccine and for at least 8.5 years with the HPV 16L1 virus-like particle of the quadrivalent vaccine. HPV vaccines induce robust immune memory, as evidenced by recall of responses after revaccination, suggesting that immunization will afford long-lasting protection. An immunological marker for ongoing protection from infection would provide information to help establish best-practice deployment of these vaccines. However, while HPV-specific antibody is likely the major mechanism of protection against HPV infection following immunization, available serological assays provide only a partial characterization of immune status, and no measured immune response has been shown to define immediate or future protection against HPV infection or associated disease. Future research efforts should therefore be directed towards correlating measures of virus-specific immune memory with continued protection against infection with the HPV types in the available vaccines, and towards determining the duration of cross-protection afforded by these vaccines against HPV types other than those incorporated in the vaccines. Copyright (c) 2010. Published by Elsevier Inc.
Fisher, William A; Laniado, Hila; Shoval, Hila; Hakim, Marwan; Bornstein, Jacob
Barriers to human papillomavirus (HPV) vaccine acceptability in Israel include Israel's relatively low incidence of cervical cancer; the religiously-based 80% circumcision rate in Israel, which is regarded as contributing to the lower incidence of HPV infection in the country; the fact that HPV vaccine provides immunity against only few virus types; the vaccine's high cost; and the perception that HPV transmission is associated with unacceptable sexual relations. A recent survey has demonstrated that, following media two campaigns, Israeli's level of awareness of the vaccine increased but the actual vaccination rate remained low, at approximately 10%. Survey findings also indicated that an enduring barrier to HPV vaccination is the vaccine's high cost. Recent research on a convenience sample of Israeli undergraduate women 21 to 24 years of age showed that intentions to receive HPV vaccination in the coming year were a function of women's attitudes towards getting vaccinated and their perceptions of social support for doing so. Undergraduate women who intended to be vaccinated perceived the prevention of cervical cancer, avoidance of personal health threat, and avoidance of HPV infection per se to be the advantages of undergoing HPV vaccination. Disadvantages of getting vaccinated included fear of vaccine side effects, cost of the vaccine, and newness of the vaccine, doubts about vaccines, time required to undergo multiple vaccinations, and dislike of injections. Friends', mothers' and physicians' recommendations influenced women's intentions to be vaccinated in the coming year as well. This article forms part of a regional report entitled "Comprehensive Control of HPV Infections and Related Diseases in Israel" Vaccine Volume 31, Supplement 8, 2013. Updates of the progress in the field are presented in a separate monograph entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. Copyright © 2013 Elsevier Ltd
Glenn, Wendy K; Whitaker, Noel J; Lawson, James S
Multiple viruses, including human immunodeficiency virus, Epstein Barr virus (EBV) and mouse mammary tumour virus have been identified in human milk. High risk human papillomavirus (HPV) sequences have been identified in breast cancer. The aim of this study is to determine if viral sequences are present in human milk from normal lactating women. Standard (liquid) and in situ polymerase chain reaction (PCR) techniques were used to identify HPV and EBV in human milk samples from normal lactating Australian women who had no history of breast cancer.High risk human papillomavirus was identified in milk samples of 6 of 40 (15%) from normal lactating women - sequencing on four samples showed three were HPV 16 and one was HPV 18. Epstein Barr virus was identified in fourteen samples (33%). The presence of high risk HPV and EBV in human milk suggests the possibility of milk transmission of these viruses. However, given the rarity of viral associated malignancies in young people, it is possible but unlikely, that such transmission is associated with breast or other cancers.
Glenn Wendy K
Full Text Available Abstract Background Multiple viruses, including human immunodeficiency virus, Epstein Barr virus (EBV and mouse mammary tumour virus have been identified in human milk. High risk human papillomavirus (HPV sequences have been identified in breast cancer. The aim of this study is to determine if viral sequences are present in human milk from normal lactating women. Findings Standard (liquid and in situ polymerase chain reaction (PCR techniques were used to identify HPV and EBV in human milk samples from normal lactating Australian women who had no history of breast cancer. High risk human papillomavirus was identified in milk samples of 6 of 40 (15% from normal lactating women - sequencing on four samples showed three were HPV 16 and one was HPV 18. Epstein Barr virus was identified in fourteen samples (33%. Conclusion The presence of high risk HPV and EBV in human milk suggests the possibility of milk transmission of these viruses. However, given the rarity of viral associated malignancies in young people, it is possible but unlikely, that such transmission is associated with breast or other cancers.
Vinther, J.; Rosenstierne, M.W.; Kristiansen, Karen
Background: High risk human papillomavirus (HR-HPV) infects mucosal surfaces and HR-HPV infection is required for development of cervical cancer. Accordingly, enforced expression of the early HR-HPV proteins can induce immortalisation of human cells. In most cervical cancers and cervical cancer...
Avnstorp, Magnus Balslev; Jensen, Ramon Gordon; Garnæs, Emilie
Oropharyngeal squamous cell carcinoma (OPSCC) is associated with the sexually transmitted human papillomavirus (HPV), smoking and alcohol. In Greenland, a high rate of HPV-induced cervical cancer and venereal diseases are found, which exposes the population for high risk of HPV infection. In Gree......Oropharyngeal squamous cell carcinoma (OPSCC) is associated with the sexually transmitted human papillomavirus (HPV), smoking and alcohol. In Greenland, a high rate of HPV-induced cervical cancer and venereal diseases are found, which exposes the population for high risk of HPV infection...
Westra, Tjalke Arend
Vaccinatie van 12-jarige meisjes tegen het humaan papillomavirus (HPV) dat baarmoederhalskanker kan veroorzaken, blijkt effectief en kosteneffectief te zijn. UMCG-onderzoeker Tjalke Westra rekende met behulp van modellen de lange termijn effecten door van verschillende HPV-vaccinatiescenario’s
Burger, Emily A; Lee, Kyueun; Saraiya, Mona; Thompson, Trevor D; Chesson, Harrell W; Markowitz, Lauri E; Kim, Jane J
In the United States, the burden of human papillomavirus (HPV)-associated cancers varies by racial/ethnic group. HPV vaccination may provide opportunities for primary prevention of these cancers. Herein, the authors projected changes in HPV-associated cancer burden among racial/ethnic groups under various coverage assumptions with the available first-generation and second-generation HPV vaccines to evaluate changes in racial/ethnic disparities. Cancer-specific mathematical models simulated the burden of 6 HPV-associated cancers. Model parameters, informed using national registries and epidemiological studies, reflected sex-specific, age-specific, and racial/ethnic-specific heterogeneities in HPV type distribution, cancer incidence, stage of disease at detection, and mortality. Model outcomes included the cumulative lifetime risks of developing and dying of 6 HPV-associated cancers. The level of racial/ethnic disparities was evaluated under each alternative HPV vaccine scenario using several metrics of social group disparity. HPV vaccination is expected to reduce the risks of developing and dying of HPV-associated cancers in all racial/ethnic groups as well as reduce the absolute degree of disparities. However, alternative metrics suggested that relative disparities would persist and in some scenarios worsen. For example, when assuming high uptake with the second-generation HPV vaccine, the lifetime risk of dying of an HPV-associated cancer for males decreased by approximately 60%, yet the relative disparity increased from 3.0 to 3.9. HPV vaccines are expected to reduce the overall burden of HPV-associated cancers for all racial/ethnic groups and to reduce the absolute disparity gap. However, even with the second-generation vaccine, relative disparities will likely still exist and may widen if the underlying causes of these disparities remain unaddressed. Cancer 2016;122:2057-66. © 2016 American Cancer Society. © 2016 American Cancer Society.
Ault, Kevin A
The majority of human papillomavirus (HPV) belong to the genus alpha-papillomavirus, which can be further subdivided into species and then strains. Approximately 200 strains of HPV have been identified, and the whole genomes of approximately 100 strains have been (discovered) and completely sequenced. Between 13 and 18 HPV strains have been characterized as conferring a high oncogenic risk, with 12 of these strains belonging to the HPV species 7 (HPV-18, -39, -45, -59, -68) and species 9 (HPV-16, -31, -33, -35, -52, -58, -67). While strains belonging to the same species are phylogenetically related, they may differ biologically. The available data on whether natural HPV infection infers cross protection against other related strains from the same species are equivocal. There are data to indicate that following HPV infection, there appears to be a reduced risk of contracting the same strain of HPV. However, there is also evidence to indicate that natural infection with HPV does not confer group-specific immune protection or general protection from reinfection with genital HPV mucosal types. Recent studies conducted with HPV vaccines show data on cross-protection against related HPV strains. In vitro experiments with serum from recipients of the quadrivalent HPV vaccine (HPV-6/8/16/18) show neutralization of HPV 45 pseudovirions. Cross-protection following vaccination of women (n=776) with three doses of bivalent HPV vaccine (HPV-16/18) demonstrated that, over a period of up to 4.5 years, long-term vaccine efficacy was observed for HPV-16 and -18, and vaccine efficacy was also observed against incident infection with HPV-31 and -45. These findings are supported by the results of a large study (n=18,644) in women aged 15 to 25 years vaccinated with the adjuvant bivalent HPV vaccine (HPV-16/18). Over a period of 6 months, cross-protection was observed against persistent infections with HPV-45, -31 and -52, and at 12 months, modest protection was demonstrated against
Nieto, Karen; Stahl-Hennig, Christiane; Leuchs, Barbara; Müller, Martin; Gissmann, Lutz; Kleinschmidt, Jürgen A
Cervical cancer is the second most common cancer in women worldwide. Persistent high-risk human papillomavirus (HPV) infection has been identified as the causative event for the development of this type of cancer. Recombinant adeno-associated viruses (rAAVs) are currently being developed and evaluated as vaccine vector. In previous work, we demonstrated that rAAVs administered intranasally in mice induced high titers and long-lasting neutralizing antibodies against HPV type 16 (HPV16). To extend this approach to a more human-related species, we immunized rhesus macaques (Macaca mulatta) with AAVs expressing an HPV16 L1 protein using rAAV5 and 9 vectors in an intranasal prophylactic setting. An rAAV5-L1 vector followed by a boost with rAAV9-L1 induced higher titers of L1-specific serum antibodies than a single rAAV5-L1 immunization. L1-specific antibodies elicited by AAV9 vector neutralized HPV16 pseudovirions and persisted for at least 7 months post immunization. Interestingly, nasal application of rAAV9 was immunogenic even in the presence of high AAV9 antibody titers, allowing reimmunization with the same serotype without prevention of the transgene expression. Two of six animals did not respond to AAV-mediated intranasal vaccination, although they were not tolerant, as both developed antibodies after intramuscular vaccination with HPV16 virus-like particles. These data clearly show the efficacy of an intranasal immunization using rAAV9-L1 vectors without the need of an adjuvant. We conclude from our results that rAAV9 vector is a promising candidate for a noninvasive nasal vaccination strategy.
Taberna, Miren; Inglehart, Ronald C; Pickard, Robert K L; Fakhry, Carole; Agrawal, Amit; Katz, Mira L; Gillison, Maura L
Sexual behavior and oral human papillomavirus (HPV) infection are risk factors for oral squamous cell carcinoma (OSCC). The effects of OSCC diagnosis and treatment on subsequent relationship stress and sexual behavior are unknown. Incident cases of HPV-positive or HPV-negative OSCC in patients who had a partnered relationship and partners of patients with oropharyngeal cancer were eligible for a study in which surveys were administered at diagnosis and at the 6-month follow-up time point to assess relationship distress, HPV transmission and concerns about health consequences, and sexual behavior. The frequency distributions of responses, stratified by tumor HPV status, were compared at baseline and follow-up. In total, 262 patients with OSCC and 81 partners were enrolled. Among the patients, 142 (54.2%) had HPV-positive OSCC, and 120 (45.8%) had HPV-negative OSCC. Relationship distress was infrequently reported, and 69% of patients felt that their relationship had strengthened since the cancer diagnosis. Both HPV-positive patients (25%) and their partners (14%) reported feelings of guilt or responsibility for the diagnosis of an HPV-caused cancer. Concern over sexual, but not nonsexual, HPV transmission to partners was reported by 50%. Significant declines in the frequency of vaginal and oral sexual behaviors were reported at follow-up, regardless of tumor HPV status. From baseline to 6 months, significant increases in abstinence from vaginal sex (from 10% to 34%; P Sexual behavior is an important quality-of-life outcome to assess within clinical trials. [See related editorial on pages 000-000, this issue.] Cancer 2017. © 2017 American Cancer Society. Cancer 2017;123:1156-1165. © 2016 American Cancer Society. © 2017 American Cancer Society.
Full Text Available Espen Enerly, Cecilia Olofsson, Mari NygårdDepartment of Research, Cancer Registry of Norway, Oslo, NorwayAbstract: Human papillomavirus (HPV is the main cause of cervical cancer, and many countries now offer vaccination against HPV to girls by way of government-funded national immunization programs. Monitoring HPV prevalence in adolescents could offer a near-term biological measure of vaccine impact, and urine sampling may be an attractive large-scale method that could be used for this purpose. Our objective was to provide an overview of the literature on HPV DNA detection in urine samples, with an emphasis on adolescents. We searched the PubMed database using the terms “HPV” and “urine” and identified 21 female and 14 male study populations in which HPV prevalence in urine samples was reported, four of which included only asymptomatic female adolescents. We provide herein an overview of the recruitment setting, age, urine sampling procedure, lesion type, HPV assay, and HPV prevalence in urine samples and other urogenital samples for the studies included in this review. In female study populations, concordance for any HPV type and type-specific concordance in paired urine and cervical samples are provided in addition to sensitivity and specificity. We concluded that few studies on HPV prevalence in urine samples have been performed in asymptomatic female adolescent populations but that urine samples may be a useful alternative to cervical samples to monitor changes in HPV prevalence in females in the post-HPV vaccination era. However, care should be taken when extrapolating HPV findings from urine samples to the cervix. In males, urine samples do not seem to be optimal for monitoring HPV prevalence due to a low human genomic DNA content and HPV DNA detection rate compared to other urogenital sites. In each situation the costs and benefits of HPV DNA detection in urine compared to alternative monitoring options should be carefully
Groves, Ian J; Coleman, Nicholas
Human papillomavirus (HPV) infection is associated with ~5% of all human cancers, including a range of squamous cell carcinomas (SCCs). Persistent infection by high-risk HPVs (HRHPVs) is associated with the integration of virus genomes (which are usually stably maintained as extrachromosomal episomes) into host chromosomes. Although HRHPV integration rates differ across human sites of infection, this process appears to be an integral event in HPV-associated neoplastic progression, leading to deregulation of virus oncogene expression, host gene expression modulation and further genomic instability. However, the mechanisms by which HRHPV integration occur and by which the subsequent gene expression changes take place are incompletely understood. The advent of 'next generation' sequencing (NGS) of both RNA and DNA has allowed powerful interrogation of the association of HRHPVs with human disease, including precise determination of the sites of integration and the genomic rearrangements at integration loci. In turn, these data have indicated that integration occurs through two main mechanisms: looping integration or direct insertion. Improved understanding of integration sites is allowing further investigation of the factors that provide a competitive advantage to some integrants during disease progression. Furthermore, advanced approaches to the generation of genome-wide samples have given novel insight into the three-dimensional interactions within the nucleus, that could act as another layer of epigenetic control of both virus and host transcription. It is hoped that further advances with NGS techniques and analysis will not only allow the examination of further unanswered questions regarding HPV infection but also direct new approaches to treating HPV-associated human disease. This article is protected by copyright. All rights reserved.
Kremsdorf, D; Jablonska, S; Favre, M; Orth, G
The DNAs of four human papillomaviruses (HPVs) that were found in the benign lesions of three patients suffering from epidermodysplasia verruciformis have been characterized. The flat wart-like lesions and the macular lesions of patient 1 contained two viruses, HPV-3a and HPV-8, respectively, whose genomes had previously been only partially characterized. The flat wart-like lesions of patient 2 and the macular lesions of patient 3 each contained a virus previously considered as belonging to t...
Hama, Takanori; Tokumaru, Yutaka; Fujii, Masato; Yane, Katsunari; Okami, Kenji; Kato, Kengo; Masuda, Muneyuki; Mineta, Hiroyuki; Nakashima, Torahiko; Sugasawa, Masashi; Sakihama, Noriyuki; Yoshizaki, Tomokazu; Hanazawa, Toyoyuki; Kato, Hisayuki; Hirano, Shigeru; Imanishi, Yorihisa; Kuratomi, Yuichirou; Otsuki, Naoki; Ota, Ichiro; Sugimoto, Taro; Suzuki, Shinsuke
The incidence rates of oropharyngeal squamous cell carcinoma (OPSCC) have risen steadily in the USA and in northern Europe. These increases are thought to be a consequence of persistent infection with high-risk human papillomavirus (HPV) in OPSCC patients. HPV is an emerging etiologic factor in OPSCC. In Japan, the incidence of OPSCC has significantly increased over the last three decades. However, the population of HPV-positive OPSCC patients is currently unknown. We examined the nationwide trends with regard to HPV incidence in OPSCC patients at 21 specific sites, and examined the relationship between the presence of HPV and survival in OPSCC patients in Japan. Tumor samples were obtained from patients with OPSCC prior to treatment, and HPV infection was investigated by polymerase chain reaction (PCR). Hybrid Capture 2 (HC2) was also adopted for swab examination on the surface of fresh tumors. HPV was detected by PCR in 79 (50.3%) out of 157 OPSCC patients. The clinical features of HPV-positive OPSCC were low differentiation, a tendency to involve the lateral wall, and high nodal staging. The sensitivity and specificity of HC2 were 93.7 and 96.2%, respectively, indicating its utility as a screening test. HPV-positive patients had significantly better overall survival and disease-free survival than HPV-negative patients. © 2014 S. Karger AG, Basel.
Full Text Available Gardasil ® is the first quadrivalent human papillomavirus (HPV- types 6, 11, 16, 18 recombinant vaccine approved by the FDA on June 8, 2006. It induces genotype-specific virus-neutralizing antibodies and prevents infection with HPV. Various clinical trials demonstrated a reduction in the incidence of vaccine-type-specific persistent infections and of associated moderate- and high-grade cervical dysplasias and carcinomas in situ after its use. Gardasil is currently approved by FDA for prevention of genital warts, cancers and precancerous conditions of cervix and vulva in 9-26 years old females. Three doses of 0.5 ml of gardasil each at 0, 2 and 6 months are given intramuscularly. It is contraindicated in individuals who are hypersensitive to the active substances or to any of the excipients of the vaccine, patients with bleeding abnormalities or patients on anticoagulant therapy and during pregnancy. However, the vaccine, at an estimated $300-500 per course, is too expensive for many women in developing countries. Moreover, question regarding the longevity of the protection by vaccine is still unsolved. Hence, longer studies are required to establish its real status in cancer prevention.
Bi, Qingqing; Zhang, Lei; Zhao, Ziyun; Mu, Xiaofeng; Zhang, Meilian; Wang, Peng
Persistent infection with human papillomavirus, especially high risk ones, is a necessary cause of cervical cancer. This study aimed to investigate the distribution of HPV genotypes in female outpatients from Qingdao, East China. A total of 4,534 cervical swabs from women visiting this medical institution for gynecologic care were included. HPV genotypes were examined by a PCR-based hybridization gene chip assay and liquid-based cytology analysis was used to evaluate cervical cytology. The overall HPV prevalence in this study was 32.2% (1,459/4,534). A total of 23 HPV genotypes were identified and the five most prevalent ones were HPV16 (16.1%), HPV52 (8.9%), HPV58 (7.9%), HPV6 (7.0%), and HPV53 (6.5%). Age-specific prevalence of HPV exhibited one peak at the youngest age group and the HPV positive rate decreased gradually with age growth. But high risk HPV infections were more prevalent among aged women. Besides, association between cervical cytology and HPV infection was also determined, 27.2% (1124/4,126) of women with normal cytology were HPV positive while 82.1% (335/408) of women with abnormal cytology were HPV positive. These findings give new epidemiological data and may provide guidance for the vaccination program in this area. © 2015 Wiley Periodicals, Inc.
Ferris, Daron G; Samakoses, Rudiwilai; Block, Stanley L
OBJECTIVES: We describe the final 10-year data for the long-term follow-up study of the 4-valent human papillomavirus (4vHPV) vaccine in preadolescents and adolescents. METHODS: In the base study (V501-018), 1661 sexually inactive boys and girls received the 4vHPV vaccine (early vaccination group...... [EVG], managed for 9.9 years) or a placebo at day 1, month 2, and month 6. Thereafter, at month 30, the placebo group (catch-up vaccination group [CVG], managed for 7.4 years) received the 4vHPV vaccine by using the same dosing schedule. Long-term anti-HPV type 6, 11, 16, and 18 immune responses were...... 38% to 65% higher geometric mean titers at month 7, which remained 16% to 42% higher at 10 years compared with adolescents. No cases of HPV type 6, 11, 16, and 18-related diseases were observed. Ten subjects had a persistent infection of ≥6 months duration with vaccine-type HPV and 2 subjects had...
Songock, William K; Kim, Seong-Man; Bodily, Jason M
High-risk human papillomaviruses (HPVs) encode oncoproteins which manipulate gene expression patterns in the host keratinocytes to facilitate viral replication, regulate viral transcription, and promote immune evasion and persistence. In some cases, oncoprotein-induced changes in host cell behavior can cause progression to cancer, but a complete picture of the functions of the viral oncoproteins in the productive HPV life cycle remains elusive. E7 is the HPV-encoded factor most responsible for maintaining cell cycle competence in differentiating keratinocytes. Through interactions with dozens of host factors, E7 has an enormous impact on host gene expression patterns. In this review, we will examine the role of E7 specifically as a regulator of transcription. We will discuss mechanisms of regulation of cell cycle-related genes by E7 as well as genes involved in immune regulation, growth factor signaling, DNA damage responses, microRNAs, and others pathways. We will also discuss some unanswered questions about how transcriptional regulation by E7 impacts the biology of HPV in both benign and malignant conditions. Copyright © 2016 Elsevier B.V. All rights reserved.
Barcellos, Regina Bones; Almeida, Sabrina Esteves de Matos; Sperhacke, Rosa Dea; Verza, Mirela; Rosso, Franciele; Medeiros, Rúbia Marília de; Perizzolo, Paulo Fernando; Cortez-Herrera, Elizabeth; Rossetti, Maria Lucia Rosa
Persistent infection with high-risk human papillomavirus (HR-HPV) has been associated with cervical cancer. Developing assays for the identification of these viral types is of great importance for monitoring patients and controlling strategies. The development of the MCHA (microplate colorimetric hybridization assay), a PCR-based method for identifying six of the most common HR-HPV types (HPV 16, 18, 31, 33, 39 and 45) is described. The MCHA combines the amplification with the GP5+/GP6+ consensus primers followed by PCR reverse hybridization with specific probes and detection through a colorimetric assay. The performance of the MCHA was evaluated using 108 DNA samples typed previously by the PapilloCheck(®). The agreement between both methods was 69.4% for HPV 16; 79.1% for HPV 45; 82.4% for HPV 18; 93.6% for HPV 31; 87.9% for HPV 33, and 17.6% for HPV 39. The assay had higher sensitivity than the Papillocheck(®), particularly for identifying HPV 16 and 18. The MCHA seemed to be sensitive and specific for the identification of the most prevalent HPV types in invasive cervical cancer, HPV 16, 18, 45, 33 and 31. It requires low-cost reagents and common laboratory apparatus. Copyright © 2011 Elsevier B.V. All rights reserved.
Lee, Sin Hang; Vigliotti, Veronica S; Pappu, Suri
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.
Kukimoto, Iwao; Mori, Seiichiro; Aoyama, Satoru; Wakae, Kousho; Muramatsu, Masamichi; Kondo, Kazunari
Persistent infection with oncogenic human papillomavirus (HPV) causes cervical cancer. However, viral genetic changes during cervical carcinogenesis are not fully understood. Recent studies have revealed the presence of adenine/thymine-clustered hypermutation in the long control region of the HPV16 genome in cervical intraepithelial neoplasia (CIN) lesions, and suggested that apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) proteins, which play a key role in innate immunity against retroviral infection, potentially introduce such hypermutation. This study reports for the first time the detection of adenine/thymine-clustered hypermutation in the E2 gene of HPV16 isolated from clinical specimens with low- and high-grade CIN lesions (CIN1/3). Differential DNA denaturation PCR, which utilizes lower denaturation temperatures to selectively amplify adenine/thymine-rich DNA, identified clusters of adenine/thymine mutations in the E2 gene in 4 of 11 CIN1 (36.4%), and 6 of 27 CIN3 (22.2%) samples. Interestingly, the number of mutations per sample was higher in CIN3 than in CIN1. Although the relevance of E2 hypermutation in cervical carcinogenesis remains unclear, the observed hypermutation patterns strongly imply involvement of APOBEC3 proteins in editing the HPV16 genome during natural viral infection. © 2015 Wiley Periodicals, Inc.
Bartosik, Martin; Durikova, Helena; Vojtesek, Borivoj; Anton, Milan; Jandakova, Eva; Hrstka, Roman
Cervical cancer, being the fourth leading cause of cancer death in women worldwide, predominantly originates from a persistent infection with a high-risk human papillomavirus (HPV). Detection of DNA sequences from these high-risk strains, mostly HPV-16 and HPV-18, represents promising strategy for early screening, which would help to identify women with higher risk of cervical cancer. In developing countries, inadequate screening options lead to disproportionately high mortality rates, making a fast and inexpensive detection schemes highly important. Electrochemical sensors and assays offer an alternative to current methods of detection. We developed an electrochemical-chip based assay, in which target HPV DNA is captured via magnetic bead-modified DNA probes, followed by an antidigoxigenin-peroxidase detection system at screen-printed carbon electrode chips, enabling parallel measurements of eight samples simultaneously. We show sensitive detection in attomoles of HPV DNA, selective discrimination between HPV-16 and HPV-18 and good reproducibility. Most importantly, we show application of the assay into both cancer cell lines and cervical smears from patients. The electrochemical results correlated well with standard methods, making this assay potentially applicable in clinical practice. Copyright © 2016 Elsevier B.V. All rights reserved.
Shew, Marcia L; Ermel, Aaron C; Tong, Yan; Tu, Wanzhu; Qadadri, Brahim; Brown, Darron R
Redetection of a type-specific human papillomavirus (HPV) infection may represent reinfection. However, a growing body of literature suggests that reactivation of HPV is common and that episodic detection of a HPV infection may represent reactivation of a persistent virus. A cohort of prospectively followed adolescent women (N = 150), ages 14-17, was observed on average 6.4 years. The authors describe the redetection of 37 HPV types and associated factors of redetection of high-risk (HR) and low-risk (LR) types using Cox proportional hazard models. Of 1,248 HPV type-specific infections, 286 (22.9%) were associated with redetection after apparent clearance. Chlamydia infections (HR = 1.99 [95%CI, 1.15-3.49]) and non-condom use (HR = 1.1 [95%CI, 1.04-1.99]) were associated with increased redetection of HR-HPV infections. Oral contraceptive pills (HR = 2.73 [95%CI, 1.52-4.90]) and number of sexual partners (HR = 1.44 [95%CI, 1.04-1.99]) were associated with increased redetection of LR-HPV infections. Episodic detection of HPV is common for HR- and LR-HPV types. This finding and identified factors or redetection have clinical implications and enhances the understanding of HPV natural history. © 2015 Wiley Periodicals, Inc.
Cook, Robert L.; Thompson, Erika L.; Kelso, Natalie E.; Friary, John; Hosford, Jennifer; Barkley, Phillip; Dodd, Virginia J.; Abrahamsen, Martha; Ajinkya, Shaun; Obesso, Peter Daniel; Rashid, Mohammed H.; Giuliano, Anna R.
Background Oral human papillomavirus (HPV) is associated with a rising incidence of certain head and neck cancers, and oral sex has been associated with oral HPV. This study sought to identify more specific patterns of oral sexual activity, including self-inoculation, that are associated with oral HPV infections in young women. Methods A total of 1010 women attending a large university completed a computer-based questionnaire and provided oral specimens that were tested for any oral HPV using a Linear Array assay that detects any HPV as well as 37 HPV genotypes. Twenty-seven women provided additional samples up to 12 months after enrollment. Bivariable and multivariable analyses were conducted to identify oral sexual patterns and other risk factors associated with prevalent oral HPV. Results Nineteen women had prevalent oral HPV (1.9%), with 10 women (1%) having a type-specific infection. Oral HPV was significantly associated with lifetime coital sex partnership numbers (P = 0.03), lifetime and yearly oral sex partnership numbers (P lipstick, or toothbrushes (P < 0.05 for each), with an apparent dose-response for alcohol use and smoking behavior, stratified by number of sexual partners. Of 7 women with prevalent HPV who provided follow-up samples, none had evidence of a persistent type-specific infection. Conclusions These data provide additional evidence of transmission of oral HPV from oral sexual activity and also suggest possible transmission from self-inoculation or sharing of oral products. PMID:25013976
Lee, Sin Hang, E-mail: email@example.com; Vigliotti, Jessica S.; Vigliotti, Veronica S.; Jones, William [Department of Pathology, Milford Hospital, 300 Seaside Ave., Milford, CT 06460 (United States)
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.
Obalek, S; Jablonska, S; Favre, M; Walczak, L; Orth, G
To identify the papillomavirus types associated with condylomata acuminata in children and to evaluate their mode of transmission, we studied 32 children with anogenital warts. External condylomata were found in 12 of their mothers and in 10 of their fathers. Ten mothers, including two without external lesions, had cervical condylomata. Blot hybridization studies disclosed a genital human papillomavirus (HPV) in 14 of 27 children (HPV-6 in 12 and HPV-11 in two) and in 8 of 14 patients (HPV-6 in all). HPV-6 was found in another child by the polymerase chain reaction technique. Infection occurred most likely at birth or from nonsexual contact, but sexual abuse could not be excluded in one 11-year-old girl. Cutaneous HPV-2 was found in seven children and as yet uncharacterized papillomaviruses were found in two children. Three mothers of HPV-2-infected children had common hand warts, and two children had subungual warts. This study shows the frequent nonsexual transmission of genital papillomaviruses in children and the unexpectedly high association of children's condylomata with papillomaviruses responsible for skin warts, possibly transmitted by heteroinoculation or autoinoculation.
Full Text Available Naked DNA vaccines can be manufactured simply and are stable at ambient temperature, but require improved delivery technologies to boost immunogenicity. Here we explore in vivo electroporation for multivalent codon-optimized human papillomavirus (HPV L1 and L2 DNA vaccination.Balb/c mice were vaccinated three times at two week intervals with a fusion protein comprising L2 residues ∼11-88 of 8 different HPV types (11-88×8 or its DNA expression vector, DNA constructs expressing L1 only or L1+L2 of a single HPV type, or as a mixture of several high-risk HPV types and administered utilizing electroporation, i.m. injection or gene gun. Serum was collected two weeks and 3 months after the last vaccination. Sera from immunized mice were tested for in-vitro neutralization titer, and protective efficacy upon passive transfer to naive mice and vaginal HPV challenge. Heterotypic interactions between L1 proteins of HPV6, HPV16 and HPV18 in 293TT cells were tested by co-precipitation using type-specific monoclonal antibodies.Electroporation with L2 multimer DNA did not elicit detectable antibody titer, whereas DNA expressing L1 or L1+L2 induced L1-specific, type-restricted neutralizing antibodies, with titers approaching those induced by Gardasil. Co-expression of L2 neither augmented L1-specific responses nor induced L2-specific antibodies. Delivery of HPV L1 DNA via in vivo electroporation produces a stronger antibody response compared to i.m. injection or i.d. ballistic delivery via gene gun. Reduced neutralizing antibody titers were observed for certain types when vaccinating with a mixture of L1 (or L1+L2 vectors of multiple HPV types, likely resulting from heterotypic L1 interactions observed in co-immunoprecipitation studies. High titers were restored by vaccinating with individual constructs at different sites, or partially recovered by co-expression of L2, such that durable protective antibody titers were achieved for each type
Bosch, F. Xavier; Broker, Thomas R.; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L.; Doorbar, John; Stern, Peter L.; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E.; Schiller, John T.; Markowitz, Lauri E.; Fisher, William A.; Canfell, Karen; Denny, Lynette A.; Franco, Eduardo L.; Steben, Marc; Kane, Mark A.; Schiffman, Mark; Meijer, Chris J.L.M.; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J.; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia
Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of
Markowitz, Lauri E; Tsu, Vivien; Deeks, Shelley L; Cubie, Heather; Wang, Susan A; Vicari, Andrea S; Brotherton, Julia M L
The availability of prophylactic human papillomavirus (HPV) vaccines has provided powerful tools for primary prevention of cervical cancer and other HPV-associated diseases. Since 2006, the quadrivalent and bivalent vaccines have each been licensed in over 100 countries. By the beginning of 2012, HPV vaccine had been introduced into national immunization programs in at least 40 countries. Australia, the United Kingdom, the United States, and Canada were among the first countries to introduce HPV vaccination. In Europe, the number of countries having introduced vaccine increased from 3 in 2007 to 22 at the beginning of 2012. While all country programs target young adolescent girls, specific target age groups vary as do catch-up recommendations. Different health care systems and infrastructure have resulted in varied implementation strategies, with some countries delivering vaccine in schools and others through health centers or primary care providers. Within the first 5 years after vaccines became available, few low- or middle-income countries had introduced HPV vaccine. The main reason was budgetary constraints due to the high vaccine cost. Bhutan and Rwanda implemented national immunization after receiving vaccine through donation programs in 2010 and 2011, respectively. The GAVI Alliance decision in 2011 to support HPV vaccination should increase implementation in low-income countries. Evaluation of vaccination programs includes monitoring of coverage, safety, and impact. Vaccine safety monitoring is part of routine activities in many countries. Safety evaluations are important and communication about vaccine safety is critical, as events temporally associated with vaccination can be falsely attributed to vaccination. Anti-vaccination efforts, in part related to concerns about safety, have been mounted in several countries. In the 5 years since HPV vaccines were licensed, there have been successes as well as challenges with vaccine introduction and implementation
Isaac, Andre; Kostiuk, Morris; Zhang, Han; Lindsay, Cameron; Makki, Fawaz; O'Connell, Daniel A; Harris, Jeffrey R; Cote, David W J; Seikaly, Hadi; Biron, Vincent L
The incidence of oropharyngeal squamous cell carcinoma (OPSCC) caused by oncogenic human papillomavirus (HPV) is rising worldwide. HPV-OPSCC is commonly diagnosed by RT-qPCR of HPV E6 and E7 oncoproteins or by p16 immunohistochemistry (IHC). Droplet digital PCR (ddPCR) has been recently reported as an ultra-sensitive and highly precise method of nucleic acid quantification for biomarker analysis. To validate the use of a minimally invasive assay for detection of oncogenic HPV based on oropharyngeal swabs using ddPCR. Secondary objectives were to compare the accuracy of ddPCR swabs to fresh tissue p16 IHC and RT-qPCR, and to compare the cost of ddPCR with p16 IHC. We prospectively included patients with p16+ oral cavity/oropharyngeal cancer (OC/OPSCC), and two control groups: p16- OC/OPSCC patients, and healthy controls undergoing tonsillectomy. All underwent an oropharyngeal swab with ddPCR for quantitative detection of E6 and E7 mRNA. Surgical specimens had p16 IHC performed. Agreement between ddPCR and p16 IHC was determined for patients with p16 positive and negative OC/OPSCC as well as for healthy control patients. The sensitivity and specificity of ddPCR of oropharyngeal swabs were calculated against p16 IHC for OPSCC. 122 patients were included: 36 patients with p16+OPSCC, 16 patients with p16-OPSCC, 4 patients with p16+OCSCC, 41 patients with p16-OCSCC, and 25 healthy controls. The sensitivity and specificity of ddPCR of oropharyngeal swabs against p16 IHC were 92 and 98% respectively, using 20-50 times less RNA than that required for conventional RT-qPCR. Overall agreement between ddPCR of tissue swabs and p16 of tumor tissue was high at ĸ = 0.826 [0.662-0.989]. Oropharyngeal swabs analyzed by ddPCR is a quantitative, rapid, and effective method for minimally invasive oncogenic HPV detection. This assay represents the most sensitive and accurate mode of HPV detection in OPSCC without a tissue biopsy in the available literature.
Herrero, Rolando; González, Paula; Markowitz, Lauri E
Oncogenic human papillomavirus (HPV) infection is the cause of nearly all cervical cancers and a proportion of other anogenital and oropharyngeal cancers. A bivalent vaccine containing HPV 16 and 18 and a quadrivalent vaccine containing HPV 6, 11, 16, and 18 antigens are in use in vaccination programmes around the world. In clinical trials, three vaccine doses provided 90-100% protection against cervical infection and pre-cancer related to HPV 16 and 18 in women aged 15-26 years who were not infected at vaccination. Partial cross-protection against other HPV types has been reported but its duration is unknown. The vaccines were also efficacious at the prevention of HPV 16 and 18 infections at other anatomical sites in both sexes. Immunobridging studies allowed licensing of the vaccines for use starting at age 9 years for both sexes. Two-dose schedules elicit high antibody concentrations, leading to the recommendation of two-dose schedules for girls aged 9-14 years. Pre-licensure and post-licensure studies have provided data supporting vaccine safety. In 2014, a nonavalent vaccine containing HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58 antigens was licensed by the US Food and Drug Administration. HPV vaccination was first introduced in high-income countries owing to vaccine cost, logistic challenges, and competing health priorities. Since 2011, vaccine prices have lowered, allowing the introduction of the vaccine in some middle-income countries. Funding of the vaccine by the GAVI Alliance in 2012 led to demonstration projects in some low-income countries. By 2014, more than 57 countries had included the HPV vaccine in their national health programmes. Data from several countries have shown the effect of vaccination on HPV infection and associated disease, and provided evidence of herd immunity. Expansion of programmes to countries with the highest burden of disease is beginning, but further efforts are needed to realise the potential of HPV vaccines. Copyright © 2015
Bosch, F Xavier; Broker, Thomas R; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L; Doorbar, John; Stern, Peter L; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E; Schiller, John T; Markowitz, Lauri E; Fisher, William A; Canfell, Karen; Denny, Lynette A; Franco, Eduardo L; Steben, Marc; Kane, Mark A; Schiffman, Mark; Meijer, Chris J L M; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia
Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of
Joura, Elmar A.; Ault, Kevin A.; Bosch, F. Xavier
BACKGROUND: We estimated the prevalence and incidence of 14 human papillomavirus (HPV) types (6/11/16/18/31/33/35/39/45/51/52/56/58/59) in cervicovaginal swabs, and the attribution of these HPV types in cervical intraepithelial neoplasia (CIN), and adenocarcinoma in situ (AIS), using predefined...
Coelho, Pedro Luiz Spinelli; da Silva Calestini, Gustavo Lacerda; Alvo, Fernando Salgueiro; de Moura Freitas, Jefferson Michel; Castro, Paula Marcela Vilela; Konstantyner, Tulio
To identify and quantify the adverse effects associated with the recombinant human papillomavirus (types 6, 11, 16 and 18) vaccine in adolescents. Systematic review of randomized clinical trials from PubMed, SciELO and Lilacs databases. Articles investigating the safety of the vaccine in subjects under 18 years and comparing the recombinant human papillomavirus types 6, 11, 16 and 18 vaccine with a control group were included. Meta-analyses were performed for the outcomes of pain, erythema, swelling and fever, using clinical trials with maximum Jadad score. Fourteen studies were included. The most commons adverse effects related to the human papillomavirus vaccine were effects with no severity (pain, erythema, edema, and fever). Five studies were used for the meta-analyses: Pain-Risk Difference (RD)=11% (p<0.001); edema-RD=8% (p<0.001); erythema-RD=5% (p<0.001); fever-RD=2% (p<0.003). The recombinant human papillomavirus types 6, 11, 16 and 18 vaccine was safe and well tolerated. The main adverse effects related to vaccination were pain, erythema, edema and fever. The low frequency of severe adverse effects encourages the administration of the vaccine in the population at risk. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.
Lippman, S. A.; Sucupira, M. C. A.; Jones, H. E.; Luppi, C. G.; Palefsky, J.; van de Wijgert, J. H. H. M.; Oliveira, R. L. S.; Diaz, R. S.
We determined the prevalence, distribution and correlates of human papillomavirus (HPV) types in 386 mixed-income, sexually active women in Sao Paulo, Brazil. Endocervical samples were tested for HPV DNA with L1 primers MY09 and MY11, negative and indeterminate samples were retested using GP 5+/6+
Brisson, Marc; Bénard, Élodie; Drolet, Mélanie
BackgroundModelling studies have been widely used to inform human papillomavirus (HPV) vaccination policy decisions; however, many models exist and it is not known whether they produce consistent predictions of population-level effectiveness and herd effects. We did a systematic review and meta-a...
P. Møller, Sanne; Kristiansen, Maria; Norredam, Marie
Refugee children and their families may experience impaired access to healthcare; therefore, we aimed to uncover human papillomavirus (HPV) immunization patterns among a large group of refugee girls compared with Danish-born girls. We also examined possible predictors of uptake among refugee girl...
Nodulman, Jessica A.; Starling, Randall; Kong, Alberta S.; Buller, David B.; Wheeler, Cosette M.; Woodall, W. Gill
Background: In several countries worldwide, school-based human papillomavirus (HPV) vaccination programs have been successful; however, little research has explored US stakeholders' acceptance toward school-based HPV vaccination programs. Methods: A total of 13 focus groups and 12 key informant interviews (N?=?117; 85% females; 66% racial/ethnic…
J.M. van Rosmalen (Joost); I.M.C.M. de Kok (Inge); M. van Ballegooijen (Marjolein)
textabstractObjective To determine the most cost-effective screening programme for cervical cancer. Design Cost-effectiveness analysis from a societal perspective. Setting The Netherlands. Population Dutch women who have not been invited for human papillomavirus (HPV) vaccination. Methods We
Rajpert-De Meyts, E; Hørding, U; Nielsen, H W
sequences of two viruses with known transforming abilities, human papillomavirus (HPV) and Epstein-Barr virus (EBV). The polymerase chain reaction (PCR) technique was used. In none of the 19 successfully amplified samples were DNA sequences of HPV type 16 or type 18 detected. In six cases a faint trace...
Lanning, Beth; Golman, Mandy; Crosslin, Katie
Background: Human papillomavirus (HPV) vaccination rates remain relatively low, despite new recommendations found in "Healthy People 2020." Purpose: The purpose of this study was to determine vaccination rates, identify factors that influenced initiation/continuance of HPV vaccine series, and identify levels of influence for HPV health…
Glahder, Jacob-Andreas Harald; Kristiansen, Karen; Durand, Marjorie
All human papillomavirus type 16 (HPV-16) early mRNAs are polyadenylated at the poly(A) signal within the early 3' untranslated region (3'UTR). The 3'end of the early E5 open reading frame and the 3'UTR of HPV-16 is very AU-rich, with five regions similar to cytoplasmic polyadenylation elements (...
Vriend, Henrike J; Boot, Hein J; van der Sande, Marianne A B; Rossen, John
BACKGROUND: Baseline genotype-specific human papillomavirus (HPV) prevalence rates and associated risk factors per gender enable future assessment of the impact of vaccination on HPV dynamics. METHODS: Before the start of national HPV vaccination for girls, data were collected cross-sectionally in
Casciotti, Dana M.; Smith, Katherine C.; Andon, Lindsay; Vernick, Jon; Tsui, Amy; Klassen, Ann C.
Background: In 2007, legislation was proposed in 24 states and the District of Columbia for school-based human papillomavirus (HPV) vaccine mandates, and mandates were enacted in Texas, Virginia, and the District of Columbia. Media coverage of these events was extensive, and media messages both reflected and contributed to controversy surrounding…
Hansen, Christina Neigaard; Nielsen, Lone; Norrild, Bodil
Worldwide, one of the most common cancer forms diagnosed in women is cervical cancer induced by infections with high-risk human papillomaviruses (HPVs) with HPV type 16 (HPV-16) being the most frequently identified. The oncogenicity is caused mainly by expression of the oncogenes E6 and E7 leading...
Rebolj, Matejka; Pribac, Igor; Frederiksen, Maria Eiholm
Human Papillomavirus (HPV) testing has been extensively studied in randomized controlled trials of primary cervical screening. Based on encouraging results concerning its high detection rates and a high negative predictive value for high-grade cervical intraepithelial neoplasia (CIN), HPV testing...
Patel, Divya A.; Grunzweig, Katherine A.; Zochowski, Melissa K.; Dempsey, Amanda F.; Carlos, Ruth C.; Dalton, Vanessa K.
Objective: To examine gender differences in human papillomavirus (HPV) vaccine stages of change following the recommendations for permissive use of HPV vaccine in males. Participants: Students aged 18-26 attending a large, public, Midwest university in April 2010. Methods: Participants completed a self-administered, online questionnaire. HPV…
Crosby, Richard A.; DiClemente, Ralph J.; Salazar, Laura F.; Nash, Rachel; Younge, Sinead; Head, Sara
Objective: To identify associations between engaging in oral sex and perceived risk of oral cancer among college men. Also, to identify associations, and their moderating factors, between oral sex and human papillomavirus (HPV) vaccine acceptance. Methods: Young men were recruited from 2 university campuses in the South (N = 150). Men completed an…
Wachtel, MS; Boon, ME; Korporaal, H; Kok, LP
Polymerase chain reaction to detect high- risk human papillomavirus has been suggested as a gold standard for cytology. The Netherlands and Surinam were prospectively compared in regard to the proportions of Negative, Atypical Squamous Cells of Undetermined Significance, and Squamous Intraepithelial
Ambühl, Lea Maria Margareta; Baandrup, Ulrik; Dybkær, Karen
Based on the current literature, we aimed to provide an overview on Human Papillomavirus prevalence in normal pregnancies and pregnancies with adverse outcome.We conducted a systematic literature search in PubMed and Embase. Data extracted from the articles and used for analysis included HPV...
Hald, Anna K; Blaakaer, Jan
human papillomavirus (HPV) may have an etiopathogenic role in anogenital LS. The databases MEDLINE and Embase were systematically searched using the PRISMA guidelines. Twenty-seven papers were included that reported the prevalence of HPV in LS and in LS associated with neoplasia. HPV was identified in 0...
Kofoed, Kristian; Sand, Carsten; Forslund, Ola
Genital warts are caused by human papillomavirus (HPV). HPV is a leading cause of anogenital malignancies and a role of HPV in the aetiology of oro-pharyngeal cancers has been demonstrated. The frequency of oral HPV infection in patients with genital warts and the association between concomitant...
Grønhøj Larsen, C; Gyldenløve, M; Jensen, D H
A significant proportion of squamous cell carcinomas of the oropharynx (OP-SCC) are related to human papillomavirus (HPV) infection and p16 overexpression. This subgroup proves better prognosis and survival but no evidence exists on the correlation between HPV and p16 overexpression based...
Yen, Chia-Feng; Chen, Si-Fan; Lin, Lan-Ping; Hsu, Shang-Wei; Chang, Mao-Jung; Wu, Chia-Ling; Lin, Jin-Ding
The present paper aims to explore awareness and acceptability of human papillomavirus (HPV) vaccination and to identify factors influencing HPV acceptability among women with physical disabilities in Taiwan. The study participants were 438 adult women with physical disabilities, aged 18-69 years. The participants were all officially registered as…
Lindley, Lisa L.; Elkind, Julia S.; Landi, Suzanne N.; Brandt, Heather M.
Objective: To determine receipt of the human papillomavirus (HPV) vaccine among female college students by demographic/descriptive characteristics and sexual behaviors. Methods: A secondary analysis of the Spring 2009 National College Health Assessment-II was conducted with 40,610 female college students (aged 18 to 24 years) attending 4-year…
Rebolj, Matejka; Njor, Sisse H; Lynge, Elsebeth
Cervical screening with human papillomavirus (HPV) testing is less specific for high-grade cervical intraepithelial neoplasia (=CIN3) than cytology. The aim of this systematic review was to determine whether a restriction of HPV testing to women aged at least 30 years would eliminate the problem...
Lam, Janni Uyen Hoa; Rebolj, Matejka; Dugué, Pierre-Antoine
Based on cross-sectional studies, the data on protection from Human Papillomavirus (HPV) infections related to using male condoms appear inconsistent. Longitudinal studies are more informative for this purpose. We undertook a systematic review of longitudinal studies on the effectiveness of male...
Tabora, N.; Zelaya, A.; Bakkers, J.M.J.E.; Melchers, W.J.G.; Ferrera, A.
Sexually transmitted infections are a serious health problem in Honduras. Human papillomavirus (HPV) and Chlamydia trachomatis are major causes of sexually transmitted diseases. To determine the prevalence of C. trachomatis and HPV in young women, 100 female university students in Honduras were
Hauwers, K.W.M. d'; Depuydt, C.; Bogers, J.P.; Stalpaert, M.; Vereecken, A.; Wyndaele, J.J.; Tjalma, W.
AIM: To investigate whether urine is a good medium for screening and whether there is a correlation between the amount of extracted DNA and human papillomavirus (HPV)-positivity. METHODS: In the present study, 30 first-voided urine (FVU) specimens and 20 urethroglandular swabs using cervex-brushes
Lewis, J.S., Jr.; Westra, W.H.; Thompson, L.D.; Barnes, L.; Cardesa, A.; Hunt, J.L.; Williams, M.D.; Slootweg, P.J.; Triantafyllou, A.; Woolgar, J.A.; Devaney, K.O.; Rinaldo, A.; Ferlito, A.
While high risk human papillomavirus (HPV) is well established as causative and clinically important for squamous cell carcinoma (SCC) of the oropharynx, its role in non-oropharyngeal head and neck SCC is much less clearly elucidated. In the sinonasal region, in particular, although it is a
Greco, Dario; Kivi, Niina; Qian, Kui
Human papillomavirus (HPV) infection is a prerequisite of developing cervical cancer, approximately half of which are associated with HPV type 16. HPV 16 encodes three oncogenes, E5, E6, and E7, of which E5 is the least studied so far. Its roles in regulating replication and pathogenesis of HPV...
Sandfort, Jessica R.; Pleasant, Andrew
Objective: To assess students' human papillomavirus (HPV) knowledge, attitudes, and behaviors. Participants/ Methods: Students (N = 1,282) at a large, public university in the Northeast United States completed a questionnaire during February 2008 assessing HPV knowledge, prevalence, transmission, cervical cancer risk and stigma; sexual behavior,…
Savoca, S; Nardo, L G; Rosano, T F; D'Agosta, S; Nardo, F
Human papillomavirus manifestations occur with increased frequency and severity amongst sexually active people. Several therapeutic approaches have been suggested to treat this viral disease. The aim of this prospective observational study was to assess the effectiveness of CO(2) laser vaporization for human papillomavirus warts. Eighty healthy sexually active women with cytologically, colposcopically and histologically diagnosed human papillomavirus urogenital and perianal warts were enrolled and then treated by CO(2) laser (16-18 W). Male partners were also investigated, and interferon-beta was eventually administered. All patients were then followed up for twelve months consecutively. At twelve-month follow-up, warts clearance was observed in 70 (87.5%) women. Recurrence was reported in ten (12.5%) women with multiple partners and affected by flat or endophytic condiloma of the cervix. Moreover, there were no complaints of pain, scar tissue deformity or other side effects. CO(2) laser vaporization is an effective, as well as safe and simple therapeutic approach for treatment of human papillomavirus warts. Its use should be encouraged for condyloma acuminata not associated with malignancy, as well as during pregnancy.
Hauwers, K.W.M. d'; Depuydt, C.E.; Bogers, J.J.; Noel, J.C.; Delvenne, P.; Marbaix, E.; Donders, A.R.T.; Tjalma, W.A.
PURPOSE: The prevalence of penile cancer varies between 1.5 (industrialized countries) and 4.5 per 100,000 men (non-industrialized countries). Predominant histological subtype is squamous cell carcinoma (SCC). Human papillomavirus (HPV) is found in 40-46% of cases: penile cancer is considered to
Bekkers, R.L.M.; Massuger, L.F.A.G.; Bulten, J.; Melchers, W.J.G.
Cervical cancer is a major cause of death, and the second most frequent cancer in women worldwide. Many studies have indicated a causal relation between genital human papillomavirus (HPV) infections and cervical cancer. High-risk HPV genotypes have been detected in almost 100% of all cervical
Human papillomavirus (HPV) is small, double-stranded DNA virus that infects mucosal and cutaneous epithelial tissue. HPV is sexually transmitted and the viral DNA replicates extrachromosomally. The virus is non-enveloped and has an icosahedral capsid. There are approximately 118 types of HPV, which are ...
Rietbergen, M.M.; Braakhuis, B.J.M.; Moukhtari, N.; Bloemena, E.; Brink, A.; Sie, D.; Ylstra, B.; Baatenburg de Jong, R.J.; Snijders, P.J.F.; Brakenhoff, R.H.; Leemans, C.R.
Background Patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCCs) have a better prognosis than patients with HPV-negative OPSCCs. Important factors contributing to this better prognosis are relatively low numbers of local/regional recurrences (LRRs) and
Lazarczyk, Maciej; Cassonnet, Patricia; Pons, Christian; Jacob, Yves; Favre, Michel
Summary: Infections by human papillomaviruses (HPVs) are the most frequently occurring sexually transmitted diseases. The crucial role of genital oncogenic HPV in cervical carcinoma development is now well established. In contrast, the role of cutaneous HPV in skin cancer development remains a matter of debate. Cutaneous beta-HPV strains show an amazing ubiquity. The fact that a few oncogenic genotypes cause cancers in patients suffering from epidermodysplasia verruciformis is in sharp contrast to the unapparent course of infection in the general population. Our recent investigations revealed that a natural barrier exists in humans, which protects them against infection with these papillomaviruses. A central role in the function of this HPV-specific barrier is played by a complex of the zinc-transporting proteins EVER1, EVER2, and ZnT-1, which maintain cellular zinc homeostasis. Apparently, the deregulation of the cellular zinc balance emerges as an important step in the life cycles not only of cutaneous but also of genital HPVs, although the latter viruses have developed a mechanism by which they can break the barrier and impose a zinc imbalance. Herein, we present a previously unpublished list of the cellular partners of EVER proteins, which points to future directions concerning investigations of the mechanisms of action of the EVER/ZnT-1 complex. We also present a general overview of the pathogenesis of HPV infections, taking into account the latest discoveries regarding the role of cellular zinc homeostasis in the HPV life cycle. We propose a potential model for the mechanism of function of the anti-HPV barrier. PMID:19487731
Cho, Hee-Jeong; Lee, Soondong; Im, Saewon; Kim, Mi-Gyeong; Lee, Jaewoo; Lee, Hee-Jung; Lee, Keyong Ho; Kim, Sujeong; Kim, Young Bong; Oh, Yu-Kyoung
Test pharmacokinetics and biodistribution of a human papillomavirus(HPV)16L1 DNA vaccine delivered in human endogenous retrovirus envelope protein (HERV)-expressing baculovirus (AcHERV) and those of naked plasmid vaccine. HPV16L1 gene was administrated as a naked plasmid or in AcHERV to mice via intravenous and intramuscular routes. HPV16L1 gene was extracted and assayed by quantitative real-time polymerase chain reaction, which was determined to have a detection limit of 50 copies/µg genomic DNA.. Mean residence times of HPV16L1 in AcHERV were 4.8- and 272.2-fold higher than naked HPV16L1 DNA vaccines after intramuscular and intravenous administration, respectively. Naked HPV16L1 DNA levels 1 month after injection were >3 orders of magnitude lower in each tissue tested than AcHERV-delivered HPV16L1, which was retained in most tissues without specific tissue tropism. AcHERV-delivered HPV16L1 administered intramuscularly persisted at the injection sites. However, the levels of copy numbers in muscle were low (1,800/μg genomic DNA) after 1 month, and undetectable after 6 months. HPV16L1 delivered via AcHERV resides longer in the body than HPV16L1 in naked form. The lack of tissue tropism ensures the safety of AcHERV vectors for further development.
Yongcheng Dong; Qifan Kuang; Xu Dai; Rong Li; Yiming Wu; Weijia Leng; Yizhou Li; Menglong Li
The human papillomavirus 16 (HPV16) has high risk to lead various cancers and afflictions, especially, the cervical cancer. Therefore, investigating the pathogenesis of HPV16 is very important for public health. Protein-protein interaction (PPI) network between HPV16 and human was used as a measure to improve our understanding of its pathogenesis. By adopting sequence and topological features, a support vector machine (SVM) model was built to predict new interactions between HPV16 and human p...
Sonawane, Kalyani; Suk, Ryan; Chiao, Elizabeth Y; Chhatwal, Jagpreet; Qiu, Peihua; Wilkin, Timothy; Nyitray, Alan G; Sikora, Andrew G; Deshmukh, Ashish A
The burden of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is disproportionately high among men, yet empirical evidence regarding the difference in prevalence of oral HPV infection between men and women is limited. Concordance of oral and genital HPV infection among men is unknown. To determine the prevalence of oral HPV infection, as well as the concordance of oral and genital HPV infection, among U.S. men and women. Nationally representative survey. Civilian noninstitutionalized population. Adults aged 18 to 69 years from NHANES (National Health and Nutritional Examination Survey, 2011 to 2014). Oral rinse, penile swab, and vaginal swab specimens were evaluated by polymerase chain reaction followed by type-specific hybridization. The overall prevalence of oral HPV infection was 11.5% (95% CI, 9.8% to 13.1%) in men and 3.2% (CI, 2.7% to 3.8%) in women (equating to 11 million men and 3.2 million women nationwide). High-risk oral HPV infection was more prevalent among men (7.3% [CI, 6.0% to 8.6%]) than women (1.4% [CI, 1.0% to 1.8%]). Oral HPV 16 was 6 times more common in men (1.8% [CI, 1.3% to 2.2%]) than women (0.3% [CI, 0.1% to 0.5%]) (1.7 million men vs. 0.27 million women). Among men and women who reported having same-sex partners, the prevalence of high-risk HPV infection was 12.7% (CI, 7.0% to 18.4%) and 3.6% (CI, 1.4% to 5.9%), respectively. Among men who reported having 2 or more same-sex oral sex partners, the prevalence of high-risk HPV infection was 22.2% (CI, 9.6% to 34.8%). Oral HPV prevalence among men with concurrent genital HPV infection was fourfold greater (19.3%) than among those without it (4.4%). Men had 5.4% (CI, 5.1% to 5.8%) greater predicted probability of high-risk oral HPV infection than women. The predicted probability of high-risk oral HPV infection was greatest among black participants, those who smoked more than 20 cigarettes daily, current marijuana users, and those who reported 16 or more
Coelho, Pedro Luiz Spinelli; Calestini, Gustavo Lacerda da Silva; Alvo, Fernando Salgueiro; Freitas, Jefferson Michel de Moura; Castro, Paula Marcela Vilela; Konstantyner, Tulio
Objective: To identify and quantify the adverse effects associated with the recombinant human papillomavirus (types 6, 11, 16 and 18) vaccine in adolescents. Data source: Systematic review of randomized clinical trials from PubMed, SciELO and Lilacs databases. Articles investigating the safety of the vaccine in subjects under 18 years and comparing the recombinant human papillomavirus types 6, 11, 16 and 18 vaccine with a control group were included. Meta-analyses were performed for the outcomes of pain, erythema, swelling and fever, using clinical trials with maximum Jadad score. Data synthesis: Fourteen studies were included. The most common adverse effects related to the human papillomavirus vaccine were effects with no severity (pain, erythema, edema, and fever). Five studies were used for the meta-analyses: pain-risk difference (RD)=11% (phuman papillomavirus types 6, 11, 16 and 18 vaccine was safe and well tolerated. The main adverse effects related to vaccination were pain, erythema, edema and fever. The low frequency of severe adverse effects encourages the administration of the vaccine in the population at risk. PMID:26376359
Sidney Roberto Nadal
outras doenças anogenitais associadas à infecção pelo HPV.Papillomavirus infection is more common in young sexually active people. It is so prevalent that from 75% to 80% of this population will be infected in their lifetime. Most lesions will be eradicated spontaneously at the point of not being detected even with the most sensible methods. Persistent infections with oncogenic HPV increase intraepithelial neoplasia and cancer risks. Two ways of prevention may be proposed: screening for precursor lesions and immunization against HPV, to avoid them. Although anogenital cancer incidence is decreasing with screening methods, costs are high and emotional disturbance may be caused by an abnormal result. So, vaccines to prevent diseases associated to HPV must be available. In the last decade, clinical tests began with several vaccines targeting the most frequent HPV types. The goal of prophylactic vaccines is to prevent primary or persistent HPV infections, and thus prevent cervical cancer and/or genital warts and the aim of the therapeutic types is to prevent progression of HPV infection, induce regression of intraepithelial neoplasia or condylomata, or eradicate residual cervical cancer. Prophylactic HPV vaccines in late stages of clinical testing are composed of HPV L1 capsid protein that self-assemble into virus-like particles (VLPs when expressed in recombinant systems, resulting in strong adaptive immune responses that are capable of neutralizing subsequent natural infections. Some studies observed 100% efficacy in preventing clinical disease for specific HPV types at least 5 years after immunization. Vaccines that target E6 and E7 proteins also represent an important strategy to control HPV-associated lesions and are in test in animal models. HPV vaccines seem to be more effective when administered prior to initiation of sexual activity, and vaccination campaigns should target preadolescent and adolescent populations. It is expected that with good coverage of the
Sentimentos vivenciados por mulheres submetidas a tratamento para Papillomavirus Humano Sentimientos vivenciados por mujeres sometidas a Tratamiento para el Papillomavirus Humano Feelings experienced by women submitted to a treatment for Human Papillomavirus
Ana Luiza Santos de Carvalho
Full Text Available A carência de informações sobre o papillomavirus humano pode gerar idéias errôneas sobre o tratamento, o que interfere no contexto sócio-familiar da mulher. Com o objetivo de conhecer os sentimentos vivenciados por mulheres submetidas a tratamento de lesões por papillomavirus humano, foi realizada uma pesquisa qualitativa de natureza exploratória com 12 mulheres, baseada na obtenção e análise de depoimentos por meio de entrevista semi-estruturada. As informações foram analisadas de acordo com a literatura e dispostas em duas temáticas: Reações emocionais e Repercussões no relacionamento. Conclui-se que a mulher que está sendo submetida a tratamento de lesões por papillomavirus humano necessita de cuidados, por parte dos enfermeiros, como forma de melhor enfrentar esse período a qual está vivenciando.La carencia de informaciones sobre el papillomavirus humano puede generar ideas erradas sobre el tratamiento, lo que interfiere en el contexto social y familiar de la mujer. Con el objetivo de conocer los sentimientos vividos por mujeres sometidas a tratamiento de lesiones por papillomavirus humanos, fue realizada una investigación cualitativa de naturaleza exploratoria con 12 mujeres, basada en la obtención y análisis de deposiciones por medio de entrevistas medio-estructurada. Las informaciones fueran analizadas conforme con la literatura y dispuestas en dos temáticas: Reacciones emocionales y Repercusiones en el reracionamiento. Concluyese que la mujer que esta siendo sometida al tratamiento de lesiones por papillomavirus humano necesita de cuidados, por parte de los enfermeros, como forma de mejor enfrentar ese periodo el cual esta viviendo.The lack of information on the papillomavirus human can generate misconception on the treatment interfering in the familiar and social context of the woman. With the purpose to know the feelings experienced by women submitted to treatment of lesions by human papillomavirus, was carried
Full Text Available The World Health Organization (WHO serves as a key organization to bring together experts along the continuum of vaccine development and regulatory approval, among its other functions. Using the revision of WHO's guidelines on prophylactic human papillomavirus (HPV vaccine as an example, we describe the process by which (1 a need to revise the guidelines was identified; (2 a group of stakeholders with complementary expertise and key questions were identified; (3 a scientific review was conducted; (4 consensus on revisions was achieved; (5 guidelines were updated, reviewed widely, and approved. This multi-year process resulted in the consensus that regulatory agencies could consider additional endpoints, such as persistent HPV infection or immune equivalence, depending on the design of the HPV vaccine trials. Updating the guidelines will now accelerate vaccine development, reduce costs of clinical trials, and lead to faster regulatory approval. Keywords: HPV vaccine, WHO, Policy guidelines
Ruge, S; Felding, C; Skouby, S O
In a randomized study, we have evaluated the treatment of cervical human papillomavirus (HPV) lesions by CO2 laser vaporization. Fifty patients with abnormal Papanicolaou smears and histological evidence of cervical HPV infection associated or not with cervical intraepithelial neoplasia (CIN) grade...... I were randomized to either a treatment or a control group. The cervical swabs were obtained every 3 months in both groups and examined for HPV type 16 DNA by the polymerase chain reaction. After a follow-up period of 12 months no significant differences were found between the laser treatment...... in their cervical smears at 12 months' follow-up was identical in the two groups, supporting the hypothesis that HPV is a persistent infection during which the virus is widespread in the vaginal epithelium....
Doelmatigheid van Humaan papillomavirus-vaccinatie--schattingen op basis van Nederlandse kosteneffectiviteitanalyses. [Efficiency of human papillomavirus vaccination--estimates based on Dutch cost effectiveness analyses
Westra, T.A.; Daemen, T.; Postma, M.J.; Wilschut, J.C.
Up to now the turnout for the human papillomavirus (HPV) vaccination programme implemented this year in the Netherlands has been lower than expected. This may be the result of negative publicity and doubts about the efficacy of the vaccination programme. To provide some clarity about the efficacy,
S. A. Tonon
Full Text Available Objective: To assess the prevalence and potential risk factors associated with human papillomavirus (HPV cervical infection among women residing in a region of northeastern Argentina with a high incidence of cervical cancer.
Newall, Anthony T.; Brotherton, Julia M. L.; Quinn, Helen E.; McIntyre, Peter B.; Backhouse, Josephine; Gilbert, Lynn; Esser, Mark T.; Erick, Joanne; Bryan, Janine; Formica, Neil; MacIntyre, C. Raina
Background. Representative population-based data on human papillomavirus (HPV) epidemiology are important for public health decision making but are difficult to obtain. Seroepidemiology is a valuable tool, although the relationship between HPV infection and seropositivity is incomplete. Methods. We
Walline, Heather M; Komarck, Chris; McHugh, Jonathan B; Byrd, Serena A; Spector, Matthew E; Hauff, Samantha J; Graham, Martin P; Bellile, Emily; Moyer, Jeffrey S; Prince, Mark E; Wolf, Gregory T; Chepeha, Douglas B; Worden, Francis P; Stenmark, Matthew H; Eisbruch, Avraham; Bradford, Carol R; Carey, Thomas E
IMPORTANCE Human papillomaviruses are now recognized as an etiologic factor in a growing subset of head and neck cancers and have critical prognostic importance that affects therapeutic decision making...
Chong, Pei Pei; Tung, Chee Hong; Rahman, Nurul Asyikin bt Abdul; Yajima, Misako; Chin, Fee Wai; Yeng, Crystale Lim Siew; Go, Eng Soon; Chan, Cordelia M. L; Yawata, Nobuyo; Yamamoto, Naoki
The aim of the study was to determine the prevalence of human papillomavirus (HPV) in primary and recurrent pterygia samples collected from different ethnic groups in the equatorial Malay Peninsula...
Foresta, Carlo; Patassini, Cristina; Bertoldo, Alessandro; Menegazzo, Massimo; Francavilla, Felice; Barzon, Luisa; Ferlin, Alberto
Human papillomaviruses (HPVs) are agents of the most common sexually transmitted diseases in females and males. Precise data about the presence, mechanism of infection and clinical significance of HPV in the male reproductive tract and especially in sperm are not available. Here we show that HPV can infect human sperm, it localizes at the equatorial region of sperm head through interaction between the HPV capsid protein L1 and syndecan-1. Sperm transfected with HPV E6/E7 genes and sperm exposed to HPV L1 capsid protein are capable to penetrate the oocyte and transfer the virus into oocytes, in which viral genes are then activated and transcribed. These data show that sperm might function as vectors for HPV transfer into the oocytes, and open new perspectives on the role of HPV infection in males and are particularly intriguing in relation to assisted reproduction techniques. PMID:21408100
Full Text Available Human papillomaviruses (HPVs are agents of the most common sexually transmitted diseases in females and males. Precise data about the presence, mechanism of infection and clinical significance of HPV in the male reproductive tract and especially in sperm are not available. Here we show that HPV can infect human sperm, it localizes at the equatorial region of sperm head through interaction between the HPV capsid protein L1 and syndecan-1. Sperm transfected with HPV E6/E7 genes and sperm exposed to HPV L1 capsid protein are capable to penetrate the oocyte and transfer the virus into oocytes, in which viral genes are then activated and transcribed. These data show that sperm might function as vectors for HPV transfer into the oocytes, and open new perspectives on the role of HPV infection in males and are particularly intriguing in relation to assisted reproduction techniques.
Foresta, Carlo; Patassini, Cristina; Bertoldo, Alessandro; Menegazzo, Massimo; Francavilla, Felice; Barzon, Luisa; Ferlin, Alberto
Human papillomaviruses (HPVs) are agents of the most common sexually transmitted diseases in females and males. Precise data about the presence, mechanism of infection and clinical significance of HPV in the male reproductive tract and especially in sperm are not available. Here we show that HPV can infect human sperm, it localizes at the equatorial region of sperm head through interaction between the HPV capsid protein L1 and syndecan-1. Sperm transfected with HPV E6/E7 genes and sperm exposed to HPV L1 capsid protein are capable to penetrate the oocyte and transfer the virus into oocytes, in which viral genes are then activated and transcribed. These data show that sperm might function as vectors for HPV transfer into the oocytes, and open new perspectives on the role of HPV infection in males and are particularly intriguing in relation to assisted reproduction techniques.
Remm, M.; Brain, R.; Jenkins, J R
Human papillomaviruses (HPV-s) have been shown to possess transforming and immortalizing activity for many different, mainly keratinocyte cell lines and they have been detected in 90% of anogenital cancer tissues, which suggests a causative role in the induction of anogenital and other tumours. We have exploited a quantitative assay to identify and characterize the origin of replication of the human papillomavirus type 18 (HPV-18), one of the most prevalent types in the high-risk HPV group. R...
Forslund, Ola; Johansson, Hanna; Madsen, Klaus Gregaard
Human papillomavirus (HPV) types from the Betapapillomavirus and Gammapapillomavirus genera are common at cutaneous sites. The aim of this study was to analyze the prevalence of these HPV types in oral and nasal samples....... Human papillomavirus (HPV) types from the Betapapillomavirus and Gammapapillomavirus genera are common at cutaneous sites. The aim of this study was to analyze the prevalence of these HPV types in oral and nasal samples....
Ozbun, Michelle A; Patterson, Nicole A
Papillomaviruses have a strict tropism for epithelial cells, and they are fully reliant on cellular differentiation for completion of their life cycles, resulting in the production of progeny virions. Thus, a permissive environment for full viral replication in vitro-wherein virion morphogenesis occurs under cooperative viral and cellular cues-requires the cultivation of epithelium. Presented in the first section of this unit is a protocol to grow differentiating epithelial tissues that mimic many important morphological and biochemical aspects of normal skin. The technique involves growing epidermal cells atop a dermal equivalent consisting of live fibroblasts and a collagen lattice. Epithelial stratification and differentiation ensues when the keratinocyte-dermal equivalent is placed at the air-liquid interface. The apparent floating nature of the cell-matrix in this method led to the nickname "raft" cultures. The general technique can be applied to normal low passage keratinocytes, to cells stably transfected with papillomavirus genes or genomes, or keratinocytes established from neoplastic lesions. However, infectious papillomavirus particles have only been isolated from organotypic epithelial cultures initiated with cells that maintain oncogenic human papillomavirus genomes in an extrachomosomal replicative form. The second section of this unit is dedicated to a virion isolation method that minimizes aerosol and skin exposure to these human carcinogens. Although the focus of the protocols is on the growth of tissues that yields infectious papillomavirus progeny, this culture system facilitates the investigation of these fastidious viruses during their complex replicative cycles, and raft tissues can be manipulated and harvested at any point during the process. Importantly, a single-step virus growth cycle is achieved in this process, as it is unlikely that progeny virions are released to initiate subsequent rounds of infection. Copyright © 2014 John Wiley
Full Text Available The problem of diagnosis, prevention and treatment of diseases caused by human papilloma virus (HPV, in recent years has become more urgent, not only for physicians, scientists, but also for patients. This is due to the high contagiousness of HPV, its prevalence and, of course, proved oncogenicity. Creation and introduction of preventive vaccines against the most common HPV types played a definite role in the global health, and, of course, raised the attention of doctors and the public to human papillomavirus infection and associated diseases. At the same time propaganda against vaccination blocks the widespread adoption of this disease prevention in our country. In this paper, we introduce the American experience of monitoring vaccination adverse events.Key words: human papillomavirus infection, prevention, vaccination, adverse events, monitoring, children.
Griep, A.E.; Lambert, P.F. [Univ. of Wisconsin School of Medicine, Madison, WI (United States)
Human papillomaviruses are believed to be etiologic agents for the majority of human cervical carcinoma, a common cancer that is a leading cause of death by cancer among women worldwide. In cervical carcinoma, a subset of papillomaviral genes, namely E6 and E7, are expressed. In vitro tissue culture studies indicate that HPV E6 and E7 are oncogenes, and that their oncogenicity is due in part to their capacity to inactivate cellular tumor suppressor genes. The behavior of E6 and E7 in vitro and the genetic evidence from analysis of human cancers suggest that the E6 and E7 genes play a significant role in the development of cervical cancer. This hypothesis is now being tested using animal models. In this review, we summarize our current knowledge of the oncogenicity of papillomavirus genes that has been generated through their study in transgenic mice. 82 refs., 4 figs., 1 tab.
Orlando, Paul A; Gatenby, Robert A; Giuliano, Anna R; Brown, Joel S
We address the ecological and evolutionary dynamics of human papillomavirus (HPV) that lead to the dichotomy between high-risk (HR) and low-risk (LR) types. We hypothesize that HPV faces an evolutionary tradeoff between persistence and per-contact transmission probability. High virion production enhances transmissibility but also provokes an immune response leading to clearance and limited persistence. Alternatively, low virion production increases persistence at the cost of diminished transmission probability per sexual contact. We propose that LR HPV types use the former strategy and that HR types use the latter. Sexual behaviors in a host population determine the success of each strategy. We develop an evolutionary model of HPV epidemiology, which includes host sexual behavior, and we find evolutionarily stable strategies of HPV. A slow turnover of sexual partners favors HR HPV, whereas high frequency of partner turnover selects for LR. When both sexual behaviors exist as subcultures in a population, disruptive selection can result in the coevolution and ecological coexistence of both HR and LR HPV types. Our results indicate that the elimination of HR HPV through vaccines may alter the evolutionary trajectory of the remaining types and promote evolution of new HR HPV types.
Chen, Xue; Liu, Hongyang; Wang, Zhirong; Wang, Shuo; Zhang, Ting; Hu, Meili; Qiao, Liang; Xu, Xuemei
The neutralizing antibodies elicited by human papillomavirus (HPV) major capsid protein L1 virus-like particle (VLP)-based vaccines are largely type-specific. An HPV vaccine inducing cross-neutralizing antibodies broadly will be cost-effective and of great value. To this end, we constructed HPV16L1-58L2 chimeric VLP (cVLP) by displaying HPV58 L2 aa.16-37 on the DE surface region of HPV16 L1. We found that vaccination with the HPV16L1-58L2 cVLP formulated with alum plus monophosphoryl lipid A ...
Sílvia MB Cavalcanti
Full Text Available Two hundred and thirty paraffin-embedded biopsies obtained from female cervical lesions were tested for the presence of human papillomavirus (HPV types 6/11,16/18 and 31/33/35 DNA using non-isotopic in situ hybridization. Specimens were classified according to the Bethesda System in low grade squamous intraepithelial lesion (LSIL, high grade SIL (HSIL and squamous cell carcinoma (SCC. HPV prevalence ranged from 92.5% in LSIL to 68.5% in SCC. Benign types were prevalent in LSILs while oncogenic types infected predominantly HSILs and SCC. HPV infection showed to be age-dependent, but no significant relation to race has been detected. Patients were analyzed through a five-year period: 20.7% of the lesions spontaneously regressed while 48.9% persisted and 30.4% progressed to carcinoma. Patients submitted to treatment showed a 19.4% recurrence rate. High risk types were present in 78.6% (CrudeOR 13.8, P=0.0003 of the progressive lesions, and in 73.7% of the recurrent SILs (COR 19.3, P=0.0000001. Possible co-factors have also been evaluated: history of other sexually transmitted diseases showed to be positively related either to progression (Adjusted OR 13.0, P=0.0002 or to recurrence (AOR 17.2, P=0.0002 while oral contraceptive use and tobacco smoking were not significantly related to them (P>0.1. Association of two or more co-factors also proved to be related to both progression and recurrence, indicating that they may interact with HPV infection in order to increase the risk of developing malignant lesions.
Smola, Sigrun; Trimble, Connie; Stern, Peter L
It is now recognized that the immune system can be a key component of restraint and control during the neoplastic process. Human papillomavirus (HPV)-associated cancers of the anogenital tract and oropharynx represent a significant clinical problem but there is a clear opportunity for immune targeting of the viral oncogene expression that drives cancer development. However, high-risk HPV infection of the target epithelium and the expression of the E6/E7 oncogenes can lead to early compromise of the innate immune system (loss of antigen-presenting cells) facilitating viral persistence and increased risk of cancer. In these circumstances, a succession of interacting and self-reinforcing events mediated through modulation of different immune receptors, chemokine and cytokine responses (CCL20; CCL2; CCR2; IL-6; CCR7; IL-12) further promote the generation of an immune suppressive microenvironment [increased levels of Tregs, Th17, myeloid-derived suppressor cells (MDSCs) and PD-L1]. The overexpression of E6/E7 expression also compromises the ability to repair cellular DNA, leading to genomic instability, with the acquisition of genetic changes providing for the selection of advantaged cancer cells including additional strategies for immune escape. Therapeutic vaccines targeting the HPV oncogenes have shown some encouraging success in some recent early-phase clinical trials tested in patients with HPV-associated high-grade anogenital lesions. A significant hurdle to success in more advanced disease will be the local and systemic immune suppressive factors. Interventions targeting the different immunosuppressive components can provide opportunity to release existing or generate new and effective antitumour immunity. Treatments that alter the protumour inflammatory environment including toll-like receptor stimulation, inhibition of IL-6-related pathways, immune-checkpoint inhibition, direct modulation of MDSCs, Tregs and macrophages could all be useful in combination with
Full Text Available Context: Human papillomavirus (HPV and Chlamydia trachomatis are the most frequent sexually transmitted infections, usually asymptomatic. Persistent infection with high-risk HPV types and other cofactors such as the concomitant infection with C. trachomatis can represent a higher risk to develop cervical lesions; therefore, screening with sensitive methods could aid to identify women at risk. Aims: The aim is to determine the prevalence and concurrence of both infections, detected with in-house molecular methods, and to identify the risk factors associated to the infections in Mexican women. Subjects and Methods: This was a cross-sectional study including gynaecological-obstetrical medical outpatients from a Social Security Hospital in Southeast Mexico. After informed consent, cervicovaginal samples were collected and tested for HPV and C. trachomatis using polymerase chain reaction (PCR. HPV positives were further tested for high-risk HPV16, 18, 58 and low-risk 11 using real-time PCR. All methods employed were in-house. Data analyses included odds ratios (OR, Chi-square and linear regressions. Results: Women included were 233, aging 15–49 (mean 30 years, 52.8% were pregnant. For HPV and C. trachomatis testing, 230 samples were adequate, resulting in 48 (20.9% and 15 (6.5% positives, respectively; 4 (1.7% were positive to both. The most frequent genotype identified was HPV58 (25% of typified samples. C. trachomatis positives were 73% asymptomatic, none had pelvic inflammatory disease or infertility histories. The only variable associated to HPV infection was the history of previous sexually transmitted disease (OR = 3.69,P= 0.0019. Conclusions: More than 25% of the population was infected with either agent. We successfully used in-house molecular methodologies for diagnosis and typing, showing HPV and C. trachomatis prevalence consistent to previous reports. Concomitant infections were found, HPV high-risk types were involved in half of these
Tim R H Read
Full Text Available BACKGROUND: Human papillomavirus (HPV-associated oropharyngeal squamous cell carcinoma is becoming more common. We examined prevalence and risk factors for oral HPV among men who have sex with men (MSM and compared sampling and transport methods. METHODS: In 2010, 500 MSM (249 HIV-positive attending Melbourne Sexual Health Centre answered a questionnaire, swabbed their mouth and throat and collected a gargled oral rinse sample. Half the oral rinse was transported absorbed in a tampon (to enable postage. HPV was detected by polymerase chain reaction, and genotyped by Roche Linear Array®. Men with HPV 16 or 18 were retested after six months. RESULTS: Any HPV genotype was detected in 19% (95% confidence intervals (CI 15-25% of HIV-infected men and 7% (95% CI 4-11% of HIV-negative men (p100 partners. Lifetime oral-penile sex partner numbers were significantly associated in a separate model: aOR 2.8(1.2-6.3 for 26-100 partners and 3.2(1.4-7.2 for>100 partners. HPV 16 and 18 persisted in 10 of 12 men after a median six months. Sensitivities of sampling methods compared to all methods combined were: oral rinse 97%, tampon-absorbed oral rinse 69%, swab 32%. CONCLUSIONS: Oral HPV was associated with HIV infection, smoking, recent tooth-brushing, and more lifetime tongue-kissing and oral sex partners. The liquid oral rinse sample was more sensitive than a tampon-absorbed oral rinse or a self-collected swab.
Bosch, F Xavier; Burchell, Ann N; Schiffman, Mark; Giuliano, Anna R; de Sanjose, Silvia; Bruni, Laia; Tortolero-Luna, Guillermo; Kjaer, Susanne Kruger; Muñoz, Nubia
Worldwide human papillomavirus (HPV) prevalence in women with normal cytology at any given point in time is approximately 10% indicating that HPV is one of the most common sexually transmitted infections. HPV-16 is consistently the most common type and HPV-18 the second with some minor regional differences. Furthermore, across the spectrum of cervical lesions, HPV-16 is consistently the most common HPV type contributing to 50-55% of invasive cervical cancer cases strongly suggesting that this viral type has a biological advantage for transmission, persistency and transformation. The same phenomenon is observed albeit at a lower level for HPV-18 and HPV-45. Sexual behavioral patterns across age groups and populations are central to the description of the HPV circulation and of the risk of infection. The concept of group sexual behavior (in addition to individual sexual behavior) is important in exploring HPV transmission and has implications for defining and monitoring HPV and cancer prevention strategies. In natural history studies, the pattern of HPV DNA prevalence by age groups is similar to the patterns of HPV incidence. Rates of exposure in young women are high and often include multiple types. There is a spontaneous and rapid decrease of the HPV DNA detection rates in the middle-age groups followed by a second rise in the post-menopausal years. This article reviews: 1) the evidence in relation to the burden of HPV infections in the world and the contributions of each HPV type to the spectrum of cervical cellular changes spanning from normal cytology to invasive cervical cancer; 2) the critical role of the patterns of sexual behavior in the populations; and 3) selected aspects of the technical and methodological complexity of natural history studies of HPV and cervical neoplasia.
Full Text Available Abstract Background Cervical cancer ranks as the first most frequent cancer among women in Benin. The major cause of cervical cancer now recognized is persistent infection of Human Papillomavirus (HPV. In Benin there is a lack of screening programs for prevention of cervical cancer and little information exists regarding HPV genotype distribution. Methods Cervical cells from 725 women were examined for the presence of viral DNA by means of a polymerase chain reaction (PCR multiplex-based assay with the amplification of a fragment of L1 region and of E6/E7 region of the HPV genome, and of abnormal cytology by Papanicolaou method. The association between HPV status and Pap test reports was evaluated. Socio-demographic and reproductive characteristics were also related. Results A total of 18 different HPV types were identified, with a prevalence of 33.2% overall, and 52% and 26.7% among women with and without cervical lesions, respectively. Multiple HPV infections were observed in 40.2% of HPV-infected women. In the HPV-testing group, the odds ratio for the detection of abnormal cytology was 2.98 (95% CI, 1.83-4.84 for HPV positive in comparison to HPV negative women. High risk types were involved in 88% of infections, most notably HPV-59, HPV-35, HPV-16, HPV-18, HPV-58 and HPV-45. In multiple infections of women with cytological abnormalities HPV-45 predominated. Conclusions This study provides the first estimates of the prevalence of HPV and type-specific distribution among women from Benin and demonstrates that the epidemiology of HPV infection in Benin is different from that of other world regions. Specific area vaccinations may be needed to prevent cervical cancer and the other HPV-related diseases.
Gilkey, Melissa B; Malo, Teri L; Shah, Parth D; Hall, Megan E; Brewer, Noel T
Improving the quality of physicians' recommendations for human papillomavirus (HPV) vaccination is critical to addressing low coverage. Thus, we sought to describe HPV vaccine communication practices among primary care physicians. Pediatricians and family physicians (n = 776) completed our national online survey in 2014. We assessed the quality of their HPV vaccine recommendations on strength of endorsement (i.e., saying the vaccine is important), timeliness (recommending it by ages 11-12), consistency (recommending it routinely vs. using a risk-based approach), and urgency (recommending same-day vaccination). A sizeable minority of physicians reported that they do not strongly endorse HPV vaccine (27%) or deliver timely recommendations for girls (26%) or boys (39%). Many physicians (59%) used a risk-based approach to recommending HPV vaccine, and only half (51%) usually recommended same-day vaccination. Overall recommendation quality was lower among physicians who were uncomfortable talking about HPV vaccine or who believed parents did not value it. Quality was higher among physicians who began discussions by saying the child was due for HPV vaccine versus giving information or eliciting questions. Many physicians in our national sample reported recommending HPV vaccine inconsistently, behind schedule, or without urgency. These practices likely contribute to under-immunization among adolescents, and may convey ambivalence to parents. As one of the first studies to assess multiple aspects of recommendation quality, these findings can inform the many state and national initiatives that aim to improve communication about HPV vaccine so as to address the persistent underuse of a powerful tool for cancer prevention. ©2015 American Association for Cancer Research.
Ebisumoto, Koji; Okami, Kenji; Maki, Daisuke; Saito, Kosuke; SHIMIZU, Fukuko; Teramura, Takanobu; Kaneda, Shoji; Iida, Masahiro
Background Several reports have suggested that selected patients with human papillomavirus?related oropharyngeal cancer can be managed with surgery alone. We retrospectively reviewed tonsillar cancer cases to analyze treatment de?intensification after transoral resection. Methods Eighteen patients with tonsillar cancer who had undergone transoral resection were included. The patients' characteristics, p16 status, adverse features, clinical course, overall survival, and relapse?free survival a...
Peralta-Rodríguez Raúl; Romero-Morelos Pablo; Villegas-Ruíz Vanessa; Mendoza-Rodríguez Mónica; Taniguchi-Ponciano Keiko; González-Yebra Beatriz; Marrero-Rodríguez Daniel; Salcedo Mauricio
Abstract Background Human Papillomavirus (HPV) in cervical epithelium has been identified as the main etiological factor in the developing of Cervical Cancer (CC), which has recently become a public health problem in Mexico. This finding has allowed for the development of vaccines that help prevent this infection. In the present study, we aimed to determine the prevalence and HPV type-distribution in Mexican women with CC, high-grade squamous intraepithelial lesion (HSIL), low-grade squamous ...
Lindley, Megan C.; Jeyarajah, Jenny; Yankey, David; Curtis, C. Robinette; Lauri E Markowitz; Stokley, Shannon
Background/Objective: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. Previous research suggests some differences between male and female adolescents in correlates of vaccine receipt and reasons for non-vaccination; few studies examine both sexes together. This analysis assessed knowledge and attitudes related to HPV disease and vaccination, intention to vaccinate, and reasons for delayed vaccination or non-vaccination among parents of boys a...
Bihl, Michel P.; Tornillo, Luigi; Kind, Andr? B.; Obermann, Ellen; Noppen, Christoph; Chaffard, Rosemarie; Wynne, Patricia; Grilli, Bruno; Foerster, Anja; Terracciano, Luigi M.; Hoeller, Sylvia
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 Hi...
Odone, A; VISCIARELLI, S.; Lalic, T; PEZZETTI, F.; Spagnoli, F.; Pasquarella, C.; G. Ferrari; SIGNORELLI, C.
SUMMARY Human papillomavirus (HPV) infection is a recognised causal factor associated with oropharyngeal cancers. The global burden of HPVrelated oropharyngeal cancers is on the increase and is predicted to surpass the burden of cervical cancer in the near future. As evidence is accumulating on the potential effectiveness of an HPV vaccine in controlling the oropharyngeal cancer epidemic; otorhinolaryngologists assume a key role ? not only in the diagnosis and treatment of HPV-related cancers...
Bissett, Sara L; Wilkinson, Dianna; Tettmar, Kate I.; Jones, Nicky; Stanford, Elaine; Panicker, Gitika; Faust, Helena; Borrow, Ray; Soldan, Kate; Unger, Elizabeth R.; Dillner, Joakim; Minor, Philip; Beddows, Simon
Suitably controlled serosurveillance surveys are essential for evaluating human papillomavirus (HPV) immunization programs. A panel of plasma samples from 18-year-old females was assembled, the majority of the samples being from recipients of the bivalent HPV vaccine. Antibody specificities were evaluated by three independent laboratories, and 3 pools that displayed no antibodies to any HPV type tested or intermediate or high levels of antibody to HPV16, HPV18, HPV31, and HPV45 were created. ...
Joaquín V. Gónzalez; Rafael A. Gutiérrez; Alicia Keszler; Maria Del Carmen Colacino; Alonio, Lidia V.; Angélica R. Teyssie; Maria Alejandra Picconi
Growing evidence suggests a role for human papillomavirus (HPV) in oral cancer; however its involvement is still controversial. This study evaluates the frequency of HPV DNA in a variety of oral lesions in patients from Argentina. A total of 77 oral tissue samples from 66 patients were selected (cases); the clinical-histopathological diagnoses corresponded to: 11 HPV- associated benign lesions, 8 non-HPV associated benign lesions, 33 premalignant lesions and 25 cancers. Sixty exfoliated cell ...
Walter, Emmanuel B; Kemper, Alex R; Dolor, Rowena J; Dunne, Eileen F
Using the Faces Pain Scale - Revised, we assessed injection site pain 10 minutes after vaccination in young females randomized to receive either quadrivalent human papillomavirus vaccine (HPV4) before or after concomitantly administered vaccines. Although pain was modestly more after HPV4 injection than after other vaccines, the pain intensity after HPV4 injection was significantly less in those who received HPV4 before receiving other concomitant vaccines.
Ge, Shichao; Gong, Bo; Cai, Xushan; Yang, Xiaoer; Gan, Xiaowei; Tong, Xinghai; Li, Haichuan; Zhu, Meijuan; Yang, Fengyun; Zhou, Hongrong; Hong, Guofan
The incidence of cervical cancer is expected to rise sharply in China. A reliable routine human papillomavirus (HPV) detection and genotyping test to be supplemented by the limited Papanicolaou cytology facilities is urgently needed to help identify the patients with cervical precancer for preventive interventions. To this end, we evaluated a nested polymerase chain reaction (PCR) protocol for detection of HPV L1 gene DNA in cervicovaginal cells. The PCR amplicons were genotyped by direct DNA...
Lee, Chang Hun; Lee, Sun Hee; Lee, Shinwon; Cho, Heerim; Kim, Kye-Hyung; Lee, Jung Eun; Jung, Eun ju; Lee, Su Jin; Kim, Eun Jung; Kim, Ki Hyung; Moon, Eunsoo; Cho, Hong Je
Background Little is known about the epidemiology on human papillomavirus (HPV) infection among HIV-infected men in Korea. The objective of this study was to determine the prevalence, genotype distribution and risk factors associated with anal HPV infection among HIV-infected men in Korea. Methods A single-center cross-sectional study was conducted with HIV-infected men in Korea. Participants completed a detailed sexual behavior risk factor questionnaire. Anal samples were collected for cytol...
Forslund, O; Hansson, B G
The genome of human papillomavirus (HPV) type 70 (HPV 70), isolated from a cervical condyloma, was obtained by cloning overlapping PCR products. By automated DNA sequence analysis, the genome was found to consist of 7,905 bp with a G + C content of 40%. The genomic organization showed the characteristic features shared by other sequenced HPVs. Nucleotide sequence comparison with previously known HPV types demonstrated the closest homology with HPV 68 (82%), HPV 39 (82%), HPV 18 (70%), HPV 45 ...
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
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 ...
Chalertpet, Kanwalat; Pakdeechaidan, Watcharapong; Patel, Vyomesh; Mutirangura, Apiwat; Yanatatsaneejit, Pattamawadee
Human papillomavirus (HPV) oncoproteins drive distinctive promoter methylation patterns in cancer. However, the underlying mechanism remains to be elucidated. Cyclin A1 (CCNA1) promoter methylation is strongly associated with HPV-associated cancer. CCNA1 methylation is found in HPV-associated cervical cancers, as well as in head and neck squamous cell cancer. Numerous pieces of evidence suggest that E7 may drive CCNA1 methylation. First, the CCNA1 promoter is methylated in HPV-positive epithe...
Patients with neck squamous cell carcinoma from unknown primary tumor (NSCCUP) present with lymph node metastases without evidence for a primary tumor. Most patients undergo an aggressive multimodal treatment, which induces severe toxicity. Primary tumors of NSCCUP can be hidden in the oropharynx. Human papillomavirus (HPV) is causally involved in a subgroup of oropharyngeal squamous cell carcinomas (OPSCC) associated with early lymph node metastasis and good prognosis. Detection of markers f...
Cameron, Ross L.; Kavanagh, Kimberley; Pan, Jiafeng; Love, John; Cuschieri, Kate; Robertson, Chris; Ahmed, Syed; Palmer, Timothy; Pollock, Kevin G.J.
In 2008, a national human papillomavirus (HPV) immunization program using a bivalent vaccine against HPV types 16 and 18 was implemented in Scotland along with a national surveillance program designed to determine the longitudinal effects of vaccination on HPV infection at the population level. Each year during 2009?2013, the surveillance program conducted HPV testing on a proportion of liquid-based cytology samples from women undergoing their first cervical screening test for precancerous ce...
Moscicki, Anna-Barbara; Ma, Yifei; Gheit, Tarik; McKay-Chopin, Sandrine; Farhat, Sepideh; Widdice, Lea E.; Tommasino, Massimo
Abstract Background. Beta (?) and gamma (?) human papillomavirus (HPV) are commonly found on the skin. Few of the ? types are associated with nonmelanoma skin cancer. Little is known about transmission patterns of these HPV, specifically in the anogenital (AG) areas. The primary objective of this study was to examine the AG concordance and transmission of ? and ?HPV types between heterosexual couples. Methods. Archival samples from a previously published study examining concordance of alpha H...
Siu, Judy Yuen-man
Background Significant others are noted to be remarkable influences in modelling children’s and young people’s health perceptions and their adoption of health behaviour. The vaccinations which a child receives are shown to be significantly influenced by his or her parents. However, there is a paucity of Chinese-based studies. When discussing the Human Papillomavirus (HPV) vaccine, very few studies examine the perceptions of Chinese parents regarding the vaccine as a preventive health measure,...
Rosa, Maria Inês; Silva, Geraldo Doneda; de Azedo Simões, Priscyla Waleska Targino; Souza, Meriene Viquetti; Panatto, Ana Paula Ronzani; Simon, Carla Sasso; Madeira, Kristian; Medeiros, Lidia Rossi
We performed a systematic review and a meta-analysis to estimate the prevalence of human papillomavirus (HPV) in ovarian cancer. A comprehensive search of the Cochrane Library, MEDLINE, CANCERLIT, LILACS, Grey literature and EMBASE was performed for articles published from January 1990 to March 2012. The following MeSH (Medical Subject Headings) terms were searched: "ovarian tumor" or "ovarian cancers" and "HPV" or "human papillomavirus." Included were case-control and cross-sectional studies, prospective or retrospective, that evaluated clinical ovarian cancer and provided a clear description of the use of in situ hybridization, Southern blot hybridization, and polymerase chain reaction. The statistical analysis was performed using REVMAN 5.0. In total, 24 primary studies were included in this meta-analysis. Studies from 11 countries on 3 continents contained data on HPV and ovarian cancer, including 889 subjects. Overall, the HPV prevalence in patients with ovarian cancer was 17.5 (95% confidence interval [CI], 15.0%-20.0%). Human papillomavirus prevalence ranged from 4.0% (95% CI, 1.7%-6.3%) in Europe to 31.4% (95% CI, 26.9%-35.9%) in Asia. An aggregate of 4 case-control studies from Asia showed an odds ratio of 2.48 (95% CI, 0.64-9.57). We found a high prevalence of HPV-positive DNA in ovarian cancer cases, but the role of HPV in ovarian cancer remains inconclusive. Further studies are needed to control case to answer this question.
Vigliotti Jessica S
Full Text Available Abstract Background Human papillomavirus (HPV genotyping is important for following up patients with persistent HPV infection and for evaluation of prevention strategy for the individual patients to be immunized with type-specific HPV vaccines. The aim of this study was to optimize a robust "low-temperature" (LoTemp™ PCR system to streamline the research protocols for HPV DNA nested PCR-amplification followed by genotyping with direct DNA sequencing. The protocol optimization facilitates transferring this molecular technology into clinical laboratory practice. In particular, lowering the temperature by 10°C at each step of thermocycling during in vitro DNA amplification yields more homogeneous PCR products. With this protocol, template purification before enzymatic cycle primer extensions is no longer necessary. Results The HPV genomic DNA extracted from liquid-based alcohol-preserved cervicovaginal cells was first amplified by the consensus MY09/MY11 primer pair followed by nested PCR with GP5+/GP6+ primers. The 150 bp nested PCR products were subjected to direct DNA sequencing. The hypervariable 34–50 bp DNA sequence downstream of the GP5+ primer site was compared to the known HPV DNA sequences stored in the GenBank using on-line BLAST for genotyping. The LoTemp™ ready-to-use PCR polymerase reagents proved to be stable at room temperature for at least 6 weeks. Nested PCR detected 107 isolates of HPV in 513 cervicovaginal clinical samples, all validated by DNA sequencing. HPV-16 was the most prevalent genotype constituting 29 of 107 positive cases (27.2%, followed by HPV-56 (8.5%. For comparison, Digene HC2 test detected 62.6% of the 107 HPV isolates and returned 11 (37.9% of the 29 HPV-16 positive cases as "positive for high-risk HPV". Conclusion The LoTemp™ ready-to-use PCR polymerase system which allows thermocycling at 85°C for denaturing, 40°C for annealing and 65°C for primer extension can be adapted for target HPV DNA
Ducancelle, A; Legrand, M C; Pivert, A; Veillon, P; Le Guillou-Guillemette, H; De Brux, M A; Beby-Defaux, A; Agius, G; Hantz, S; Alain, S; Catala, L; Descamps, P; Postec, E; Caly, H; Charles-Pétillon, F; Labrousse, F; Lunel, F; Payan, C
Cervical cancer is caused by persistent infection with high-risk human papillomavirus (HR-HPV). Conventional human papillomavirus (HPV) testing requires cervical sampling. However, vaginal and urine self-sampling methods are more acceptable for patients and result in increased participation when they are available in screening programs. In this context, we have developed a non-invasive screening method via the detection of HPV DNA in urine samples. To compare HPV viral loads and genotypes in paired cervical and urine samples, and to assess correlation between virological and cytological results in women seeking gynecological consultation. Paired urine and cervical specimens were collected and analyzed from 230 of 245 women participating in the previously described prospective PapU study. HPV DNA detection and quantification were performed using a real-time PCR method with short fragment PCR primers. Genotyping was carried out using the INNO-LiPA HPV genotyping assay. The prevalence of HPV in the 230 paired urine and cervical smear samples was 42 and 49 %, respectively. Overall agreement for HPV positivity and negativity between the paired samples was 90 % (κ = 0.80). High HPV viral load in both cervical and urine samples was associated with cytological abnormalities. HPV-positive women were mostly infected with HR-HPV types. The agreement between high- and low-risk HPV (LR-HPV) detection in both samples was 97 % (κ = 0.95 for HR-HPV and κ = 0.97 for LR-HPV). High concordance rates for HPV-DNA quantification and high/low-risk HPV genotyping in paired urine/cervical samples suggest that urinary HPV DNA testing could be useful for cervical lesion screening.
Gersch, Elizabeth D; Gissmann, Lutz; Garcea, Robert L
The currently licensed human papillomavirus (HPV) vaccines are safe and highly effective at preventing HPV infection for a select number of papillomavirus types, thus decreasing the incidence of precursors to cervical cancer. It is expected that vaccination will also ultimately reduce the incidence of this cancer. The licensed HPV vaccines are, however, type restricted and expensive, and also require refrigeration, multiple doses and intramuscular injection. Second-generation vaccines are currently being developed to address these shortcomings. New expression systems, viral and bacterial vectors for HPV L1 capsid protein delivery, and use of the HPV L2 capsid protein will hopefully aid in decreasing cost and increasing ease of use and breadth of protection. These second-generation vaccines could also allow affordable immunization of women in developing countries, where the incidence of cervical cancer is high.
Hughes, D S; Powell, N; Fiander, A N
The role of human papillomavirus (HPV) infection in eye disease is controversial. However, a recent case illustrates the possible role of HPV in conjunctival squamous carcinoma and the potentially devastating effects of this disease. The development of two vaccines to prevent infection with HPV types most commonly associated with anogenital cancers has led to debate about the pros and cons of a national immunisation programme to prevent cervical cancer. The introduction of such a vaccination programme may have an additional beneficial effect on the occurrence of some head and neck, including ocular, cancers. This review discusses the nature of papillomaviruses, mechanisms of infection and carcinogenesis, the possible role of HPV in eye disease, and finally the likely impact of the new prophylactic vaccines.
Yasumoto, S.; Burkhardt, A.L.; Doniger, J.; DiPaolo, J.A.
A biological function for human papillomavirus 16 (HPV 16) DNA was demonstrated by transformation of NIH 3T3 cells. HPV 16 DNA has been found frequently in genital cancer and has been classified as a papillomavirus on the basis of DNA homology. A recombinant HPV 16 DNA (pSHPV16d), which contains a head-to-tail dimer of the full-length HPV 16 genome, induced morphologic transformation; the transformed cells were tumorigenic in nude mice. Expression of transforming activity was unique because of the long latency period (more than 4 weeks) required for induction of morphologic transformation and because the transfected DNA existed primarily in a multimeric form with some rearrangement. Furthermore, virus-specific RNAs were expressed in the transformants. The transformation of NIH 3T3 cells provides a model for analyzing the functions of HPV 16, which is associated with cervical carcinomas.
Кристина Владимировна Марочко
Full Text Available Human papillomavirus (HPV is the most common sexually transmitted infection worldwide. About 99 % of cervical cancer is caused by persistent infection with high-risk types of HPV. It can take over 10 years from the time of an initial human papillomavirus infection until a cervical cancer. In most cases, HPV infections are transient and go away within 1 year. There is evidence that cell mediated immune responses of the host, both systemic and local, are important determinants of the course of infection, thus, it is reasonable to use immunocorrective therapy. Many studies have demonstrated the effectiveness of interferon alpha in complex therapy of HPV infection. The aim – to determine the efficacy of interferon alpha-2b in reducing the viral load of high-risk HPV among infected women of reproductive age. Materials and methods. 60 high-risk HPV positive women were included in the study. Qualitative and quantitative determination of high-risk HPV (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 was carried out by PCR in real time. Patients were randomized into two groups: group 1 (n = 30 received alfa-interferon in the form of rectal suppositories; group 2 (n = 30 did not receive the drug. Control study was conducted 1 month later. The average age in group 1 was 31,7 ± 1,6 years, in group 2 – 35,0 ± 1,6 years (p = 0,08. In group 1 monoinfection diagnosed in 72,4 % of cases, mixed infection in 27,6 % of cases in group 2 – at 64,3 % and 35,7 %, respectively. Results. The average viral load was 3,5 ± 0,2 Lg (HPV on 105 cells in group 1 and 3,4 ± 0,3 in group 2 (p = 0,473. Сlinically significant viral load dominated in group 1 (41,4 %, insignificant viral load was dominated in group 2 (42,9 %. After 1 month the average viral load was 1,9 ± 0,3 Lg (HPV on 105 cells in group 1 and 2,8 ± 0,4 Lg in group 2 (р = 0,04. There were statistically significant difference in both groups before and after 1 month (p < 0
Mitra, Anita; MacIntyre, David A; Marchesi, Julian R; Lee, Yun S; Bennett, Phillip R; Kyrgiou, Maria
The vaginal microbiota plays a significant role in health and disease of the female reproductive tract. Next-generation sequencing techniques based upon the analysis of bacterial 16S rRNA genes permit in-depth study of vaginal microbial community structure to a level of detail not possible with standard culture-based microbiological techniques. The human papillomavirus (HPV) causes both cervical intraepithelial neoplasia (CIN) and cervical cancer. Although the virus is highly prevalent, only a small number of women have a persistent HPV infection and subsequently develop clinically significant disease. There is emerging evidence which leads us to conclude that increased diversity of vaginal microbiota combined with reduced relative abundance of Lactobacillus spp. is involved in HPV acquisition and persistence and the development of cervical precancer and cancer. In this review, we summarise the current literature and discuss potential mechanisms for the involvement of vaginal microbiota in the evolution of CIN and cervical cancer. The concept of manipulation of vaginal bacterial communities using pre- and probiotics is also discussed as an exciting prospect for the field of cervical pathology.
Full Text Available Persistent cervical infection with high-risk human papillomaviruses (hrHPVs is a necessary, but not sufficient, condition for the development of cervical cancer. Therefore, there are other co-factors facilitating the hrHPV carcinogenic process, one of which is smoking. To assess the effect of smoking on high-risk (hr HPV DNA positivity and on the expression of HPV E7 oncoprotein, as a surrogate of persistent hrHPV infection, we used data from women recruited for the PIPAVIR project, which examined the role of E7 protein detection in cervical cancer screening. Women were tested for hrHPV DNA, using Multiplex Genotyping (MPG, and E7 protein, using a novel sandwich ELISA method, and gave information on their smoking habits. Among 1473 women, hrHPV prevalence was 19.1%. The odds ratio (OR for hrHPV positivity of smokers compared to non-smokers was 1.785 (95% confidence intervals (CI: 1.365–2.332, p < 0.001. The ORs for E7 positivity, concerning hrHPV positive women, ranged from 0.720 to 1.360 depending on the E7 detection assay used, but this was not statistically significant. Smoking increases the probability of hrHPV infection, and smoking intensity is positively associated to this increase. Smoking is not related to an increased probability of E7 protein positivity for hrHPV positive women.
Moreover, the subtypes of HPV involved in cervical pathology, their associations, and natural history (clearance and persistence rates) differ from the industrialized world. Therefore, the current bivalent and quadrivalent anti‑HPV vaccines are unlikely to achieve their target in the developing world. It follows from published ...
Giuliano, Anna R; Nyitray, Alan G; Kreimer, Aimée R; Pierce Campbell, Christine M; Goodman, Marc T; Sudenga, Staci L; Monsonego, Joseph; Franceschi, Silvia
Human papillomaviruses (HPVs) cause cancer at multiple anatomic sites in men and women, including cervical, oropharyngeal, anal, vulvar and vaginal cancers in women and oropharyngeal, anal and penile cancers in men...
Cranston, Ross D; Regueiro, Miguel; Hashash, Jana; Baker, Jonathan R; Richardson-Harman, Nicola; Janocko, Laura; McGowan, Ian
Defective cell-mediated immunity increases the risk of human papillomavirus-associated anal dysplasia and cancer. There is limited information on anal canal disease in patients with IBD. The purpose of this study was to assess anal/vaginal human papillomavirus and anal dysplasia prevalence in patients with IBD. Patients had an anal examination before routine colonoscopy. The study was conducted at a tertiary IBD referral center. We studied a convenience sample of sexually active male and female patients with IBD who were not on biological therapy. Anal examination, anal and vaginal human papillomavirus testing, anal cytology, and high-resolution anoscopy/biopsy were carried out. Anal and vaginal human papillomavirus types, anal cytology, and biopsy grade were measured. Twenty-five male and 21 female evaluable participants, 31 with Crohn's disease, 14 with ulcerative colitis, and 1 with indeterminate colitis, were predominantly white (91.3%), treatment experienced (76.1%), an average age of 38.1 years (range, 22.0-66.0 y), and had an average length of IBD diagnosis of 9.3 years (range, 1.0-33.0 y). Eighteen (39.1%) had an abnormal perianal examination and 3 (6.5%) had an abnormal digital examination. Forty-one (89.1%) had anal human papillomavirus, 16 with a single type and 25 with multiple types (range, 2-5 types). Human papillomavirus type 16 was most common (65.2%), followed by human papillomavirus types 11 and 45 (37.0% each). Nineteen of 21 (90.5%) women had vaginal human papillomavirus. Overall, 21 (45.7%) had abnormal anal cytology. Thirty three (71.7%) had ≥1 anal biopsy (9 had multiple), with dysplasia diagnosed in 28 (60.9%) and high-grade and low-grade squamous intraepithelial lesions diagnosed in 4 (8.7%) and 24 (43.5%). No control group was included, and no detailed sexual history was taken. A high prevalence of anal and vaginal human papillomavirus and anal dysplasia was demonstrated in the study population outcomes. See Video Abstract at http
Hughes, Sara A; Sun, Deqin; Gibson, Cheryl; Bellerose, Bronya; Rushing, Lynda; Chen, Hao; Harlow, Bernard L; Genest, David R; Sheets, Ellen E; Crum, Christopher P
This study related morphologic subtype, human papillomavirus status, and a second cytologic examination to the follow-up biopsy-proven high-grade squamous intraepithelial lesion (HSIL; grade II or III cervical intraepithelial neoplasia) after a cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS). Seven hundred four liquid-based cervical cytology specimens were classified as normal, "ASCUS, favor reactive" (AFR), "ASCUS, not otherwise specified," "ASCUS, favor low-grade squamous intraepithelial lesion," "ASCUS, favor HSIL" (AFHS), low-grade squamous intraepithelial lesion, and HSIL. Human papillomavirus typing used polymerase chain reaction-restriction fragment length polymorphism analysis. A longitudinal review of the cytologic and histologic records of ASCUS cases with > or =1 follow-up test or biopsy ascertained the frequency of a follow-up diagnosis of biopsy-proven HSIL (grade II or III cervical intraepithelial neoplasia). Three hundred eighty-six cases (208 ASCUS, 68 normal, 86 with low-grade squamous intraepithelial lesions, and 24 with HSIL) were evaluated. High-risk human papillomavirus (HRHPV positive) was lowest with normal cytology (13%), highest with HSIL (71%), and was present in 29.8% of ASCUS cases, ranging from 22.2% (AFR) to 75% (AFHS). Most ASCUS tests (64%) were followed by a negative cytologic or histologic examination. Overall, 3.8% and 11% of ASCUS and HRHPV-positive ASCUS had histologic outcomes of HSIL. AFHS had the highest (25%) and AFR had the lowest (1.1%) proportion of HSIL outcomes. Sensitivity, specificity, and positive predictive values of human papillomavirus testing for biopsy-proven HSIL were 87.5%, 72.5%, and 11.3%, respectively. HSIL and AFHS are distinguished by the highest frequency of HRHPV types and higher rates of HSIL outcome. The remaining categories of ASCUS are heterogeneous with respect to human papillomavirus type and HSIL risk, and the value of subclassification of these entities is
Lee, Do-Hoon; Hwang, Na Rae; Lim, Myong Cheol; Yoo, Chong Woo; Joo, Jungnam; Kim, Joo-Young; Park, Sang-Yoon; Hwang, Sang-Hyun
Anyplex II HPV HR (Anyplex_HR; Seegene, Seoul, Korea) is a new multiplex real-time polymerase chain reaction assay for screening cervical cancer, and it is designed to detect 14 high-risk human papillomaviruses along with all the genotype information in a single tube. The aim of this study was to evaluate the performance of the Anyplex_HR in comparison to that of the Cobas 4800 HPV (Cobas_4800; Roche Molecular Diagnostics, Pleasanton, CA, USA) and the Hybrid capture 2 (HC2; Qiagen GmbH, Hilden, Germany). The performance of the Anyplex_HR for high-risk human papillomavirus genotype detection was prospectively evaluated against that of the HC2 and the Cobas_4800 at the National Cancer Center using 400 cervical samples. All discrepant samples were confirmed by polymerase chain reaction with type-specific primers followed by sequencing. The overall agreement and kappa value of the Anyplex_HR with the Cobas_4800 were 98.0% and 0.96, respectively. The level of agreement between the two assays and the corresponding kappa values for human papillomavirus16, human papillomavirus18 and other high-risk human papillomaviruses were 99.5%, 99.8% and 98.8%, and 0.98, 0.96 and 0.97, respectively. The agreement and kappa value of the HC2 with the Cobas_4800 were 95.3% and 0.91. The human papillomavirus positivity of the Anyplex_HR and the Cobas_4800 in low-grade squamous intraepithelial lesion/high-grade squamous intraepithelial lesion samples demonstrated 100% concordance. Both the Anyplex_HR and the Cobas_4800 showed excellent results in the precision test. The Anyplex_HR is comparable with the Cobas_4800 and the HC2 for human papillomavirus DNA testing, and it may prove more useful for follow-up testing and patient management by providing genotyping information additional to human papillomavirus16 and human papillomavirus18. © The Author(s) 2016.
Everton Faccini Augusto
Full Text Available OBJECTIVES: to survey the prevalence of human papillomavirus, associated risk factors and genotype distribution in women who were referred to cervical cancer screening when attended in a Family Health Program. METHOD: we conducted a cross-sectional survey, investigating 351 women. Polymerase chain reaction for DNA amplification and restriction fragment length polymorphism analysis were used to detect and typify the papillomavirus. RESULTS: virus infection was detected in 8.8% of the samples. Among the 21 different genotypes identified in this study, 14 were high risk for cervical cancer, and the type 16 was the most prevalent type. The infection was associated with women who had non-stable sexual partners. Low risk types were associated with younger women, while the high risk group was linked to altered cytology. CONCLUSION: in this sample attended a Family Health Program, we found a low rate of papillomavirus infection. Virus frequency was associated to sexual behavior. However, the broad range of genotypes detected deserves attention regarding the vaccine coverage, which includes only HPV prevalent types.
López-Contreras, Mario; Rosales, Carlos; Magallanes-Molina, Jose-Roberto; Gonzalez-Vergara, Roberto; Arroyo-Cazarez, Jose Martin; Ricardez-Arenas, Antonio; del Follo-Valencia, Armando; Padilla-Arriaga, Santiago; Guerrero, Miriam Veronica; Pirez, Miguel Angel; Arellano-Fiore, Claudia; Villarreal, Freddy
Abstract Human papilloma viruses can induce warts, condylomas, and other intraepithelial cervical lesions that can progress to cancer. Cervical cancer is a serious problem in developing countries because early detection is difficult, and thus proper early treatment is many times missing. In this phase III clinical trial, we evaluated the potential use of MVA E2 recombinant vaccinia virus to treat intraepithelial lesions associated with papillomavirus infection. A total of 1176 female and 180 male patients with intraepithelial lesions were studied. They were injected with 107 MVA E2 virus particles directly into their uterus, urethra, vulva, or anus. Patients were monitored by colposcopy and cytology. Immune response was determined by measuring the antibody titer against MVA E2 virus and by analyzing the cytotoxic activity against cancer cells bearing papillomavirus DNA. Papillomavirus was determined by the Hybrid Capture method or by polymerase chain reaction analysis. By histology, 1051 (89.3%) female patients showed complete elimination of lesions after treatment with MVA E2. In 28 (2.4%) female patients, the lesion was reduced to CIN 1. Another 97 (8.3%) female patients presented isolated koilocytes after treatment. In men, all lesions were completely eliminated. All MVA E2–treated patients developed antibodies against the MVA E2 vaccine and generated a specific cytotoxic response against papilloma-transformed cells. Papillomavirus DNA was not detected after treatment in 83% of total patients treated. MVA E2 did not generate any apparent side effects. These data suggest that therapeutic vaccination with MVA E2 vaccine is an excellent candidate to stimulate the immune system and generate regression in intraepithelial lesions when applied locally. PMID:25275724
Multhaupt, H A; Fessler, J N; Warhol, M J
Human papillomavirus (HPV) is associated with human neoplasms of squamous epithelium. Squamous papillomas and verrucous carcinomas are two types of squamous neoplasms of the larynx that present difficult problems in differential diagnosis. Using in situ hybridization with biotinylated DNA probes...... Hospital, Philadelphia, PA. Tissue sections were hybridized with an HPV DNA cocktail. The HPV-positive cases then were subtyped further with DNA probes specific for HPV subtypes 6/11, 16/18, and 31/33/35. All benign squamous papillomas (42 of 42) were positive for HPV subtype 6/11. None of the verrucous...
Solinas-Toldo, Sabina; Dürst, Matthias; Lichter, Peter
High risk human papillomaviruses (HPVs) known to be closely associated with cervical cancer, such as HPV16 and HPV18, have the potential to immortalize human epithelial cells in culture. Four lines of HPV-transfected keratinocytes were analyzed by comparative genomic hybridization at different time points after transfection. A number of chromosomal imbalances was found to be highly characteristic for the cultures progressing toward immortality. Whereas several of these were new and previously not found as recurrent aberrations in cervical tumors, some were identical to chromosomal changes observed during cervical carcinogenesis. The data put new emphasis on the studied cell system as a relevant model for HPV-induced pathogenesis. PMID:9108068
Kaspersen, Maja Døvling; Bungum, Mona; Fedder, Jens
It remains unknown whether human papillomaviruses (HPVs) or human herpesviruses (HHVs) in semen affect sperm DNA integrity. We investigated whether the presence of these viruses in semen was associated with an elevated sperm DNA fragmentation index. Semen from 76 sperm donors was examined by a PCR......-based hybridization array that identifies all HHVs and 35 of the most common HPVs. Sperm DNA integrity was determined by the sperm chromatin structure assay. HPVs or HHVs, or both, were found in 57% of semen samples; however, sperm DNA fragmentation index was not increased in semen containing these viruses....
Hoppe-Seyler, Karin; Bossler, Felicitas; Lohrey, Claudia; Bulkescher, Julia; Rösl, Frank; Jansen, Lars; Mayer, Arnulf; Vaupel, Peter; Dürst, Matthias; Hoppe-Seyler, Felix
Human papillomaviruses (HPVs) are major human carcinogens. It is widely assumed that HPV-positive tumor cells must sustain viral E6/E7 oncogene expression to continuously block the tumor-suppressive senescence response of the host cell. Consequently, E6/E7 are considered attractive therapeutic targets for immunotherapy or for functional inhibition. Here we show that hypoxic conditions, as often found in HPV-positive cancers, allow the cells to induce a dormant state in which E6/E7 is down-reg...
Zhao, Xu-Ye; Cui, Yong; Jiang, Shu-Fang; Liu, Ke-Jun; Han, Hai-Qiong; Liu, Xiao-Su; Li, Yali
Our aims were to evaluate the clinical performance of human telomerase RNA gene component (hTERC gene) amplification assay with high-risk human papillomavirus (HR-HPV) DNA test of Hybrid Capture 2 DNA test (HC2), for the detection of high grade cervical precancerous lesions and cancer (CIN 2+). In addition, the association shown between hTERC gene amplification and HPV DNA test positive in women with and without cervical neoplasia was assessed. There were 92 women who underwent cytology, HR-HPV DNA test, hTERC gene amplification test, colposcopy and biopsy. We compared the clinical performance of hTERC gene test along with HR-HPV DNA test of women with colposcopy and routine screening. The samples were histology- confirmed high-grade cervical intraepithelial neoplasia (CIN 2) or worse (CIN2+) as the positive criterion. The test of hTERC gene showed the hTERC gene amplification positivity increased with the severity of histological abnormality and cytological abnormality. The test of hTERC gene showed higher specificity than HR-HPV DNA test for high-grade lesions (84.4% versus 50%) and also higher positive predictive value (90.4% versus 76.5%). Our results predicted that hTERC gene amplification demonstrated more specific performance for predicting the risk of progression and offer a strong potential as a tool for triage in cervical cancer screening, with the limited sensitive as HR-HPV DNA test.
Full Text Available Diagnostic assays for persistent chlamydial infection are much needed to conduct high-quality, large-scale studies investigating the persistent state in vivo, its disease associations and the response to therapy. Yet in most studies the distinction between acute and persistent infection is based on the interpretation of the data obtained by the assays developed to diagnose acute infections or on complex assays available for research only and/or difficult to establish for clinical use. Novel biomarkers for detection of persistent chlamydial infection are urgently needed. Chlamydial whole genome proteome arrays are now available and they can identify chlamydial antigens that are differentially expressed between acute infection and persistent infection. Utilizing these data will lead to the development of novel diagnostic assays. Carefully selected specimens from well-studied patient populations are clearly needed in the process of translating the proteomic data into assays useful for clinical practice. Before such antigens are identified and validated assays become available, we face a challenge of deciding whether the persistent infection truly induced appearance of the proposed marker or do we just base our diagnosis of persistent infection on the presence of the suggested markers. Consequently, we must bear this in mind when interpreting the available data.
Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial
Dillner, Joakim; Kjaer, Susanne K; Wheeler, Cosette M
To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata).......To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata)....
Kreimer, Aimée R; Pierce Campbell, Christine M; Lin, Hui-Yi; Fulp, William; Papenfuss, Mary R; Abrahamsen, Martha; Hildesheim, Allan; Villa, Luisa L; Salmerón, Jorge J; Lazcano-Ponce, Eduardo; Giuliano, Anna R
Oral human papillomavirus (HPV) infection causes a subset of oropharyngeal cancers. These cancers disproportionately affect men, are increasing in incidence, and have no proven prevention methods. We aimed to establish the natural history of oral HPV infection in men. To estimate incidence and clearance of HPV infections, men residing in Brazil, Mexico, and the USA who were HIV negative and reported no history of anogenital cancer were recruited into the HPV Infection in Men (HIM) cohort study. A subset of the cohort who provided two or more oral rinse-and-gargle samples with valid HPV results and who completed a minimum of 2 weeks of follow-up were included in this analysis. Oral rinse-and-gargle samples and questionnaire data were obtained every 6 months for up to 4 years. Samples were analysed for the presence of oncogenic and non-oncogenic HPV infections by the linear array method. 1626 men aged 18-73 years and with a median follow-up of 12·7 months (IQR 12·1-14·7) were included in the analysis. During the first 12 months of follow-up, 4·4% (95% CI 3·5-5·6; n=115 incident infections) of men acquired an incident oral HPV infection, 1·7% (1·2-2·5; n=53 incident infections) an oral oncogenic HPV infection, and 0·6% (0·3-1·1; n=18 incident infections) an oral HPV 16 infection. Acquisition of oral oncogenic HPV was significantly associated with smoking and not being married or cohabiting, but was similar across countries, age groups, and reported sexual behaviours. Median duration of infection was 6·9 months (95 % CI 6·2-9·3; n=45 cleared infections) for any HPV, 6·3 months (6·0-9·9; n=18 cleared infections) for oncogenic HPV, and 7·3 months (6·0-not estimable; n=5 cleared infections) for HPV 16. Eight of the 18 incident oral HPV 16 infections persisted for two or more study visits. Newly acquired oral oncogenic HPV infections in healthy men were rare and most were cleared within 1 year. Additional studies into the natural history of HPV are
Full Text Available BACKGROUND: Infection with high-risk human papillomavirus (HPVtypes has been recognized as a causal factor for the development of cervical cancer and a number of other malignancies. Today, vaccines against HPV, highly effective in the prevention of persistent infection and precancerous lesions, are available for the routine clinical practice. OBJECTIVES: The data on the prevalence and type-specific HPV distribution in the population of each country are crucial for the surveillance of HPV type-specific prevalence at the onset of vaccination against HPV. METHODS: Women attending a preventive gynecological examination who had no history of abnormal cytological finding and/or surgery for cervical lesions were enrolled. All samples were tested for the presence of HPV by High-Risk Hybrid Capture 2 (HR HC2 and by a modified PCR-reverse line blot assay with broad spectrum primers (BS-RLB. RESULTS: Cervical smears of 1393 women were analyzed. In 6.5% of women, atypical cytological findings were detected. Altogether, 28.3% (394/1393 of women were positive for any HPV type by BS-RLB, 18.2% (254/1393 by HR HC2, and 22.3% (310/1393 by BS-RLB for HR HPV types. In women with atypical findings the prevalence for HR and any HPV types were significantly higher than in women with normal cytological findings. Overall, 36 different HPV types were detected, with HPV 16 being the most prevalent (4.8%. HPV positivity decreased with age; the highest prevalence was 31.5% in the age group 21-25 years. CONCLUSIONS: Our study subjects represent the real screening population. HPV prevalence in this population in the Czech Republic is higher than in other countries of Eastern Europe. Also the spectrum of the most prevalent HPV types differs from those reported by others but HPV 16 is, concordantly, the most prevalent type. Country-specific HPV type-specific prevalences provide baseline information which will enable to measure the impact of HPV vaccination in the future.
Full Text Available Abstract Background To provide quantitative insight into current U.S. policy choices for cervical cancer prevention, we developed a model of human papillomavirus (HPV and cervical cancer, explicitly incorporating uncertainty about the natural history of disease. Methods We developed a stochastic microsimulation of cervical cancer that distinguishes different HPV types by their incidence, clearance, persistence, and progression. Input parameter sets were sampled randomly from uniform distributions, and simulations undertaken with each set. Through systematic reviews and formal data synthesis, we established multiple epidemiologic targets for model calibration, including age-specific prevalence of HPV by type, age-specific prevalence of cervical intraepithelial neoplasia (CIN, HPV type distribution within CIN and cancer, and age-specific cancer incidence. For each set of sampled input parameters, likelihood-based goodness-of-fit (GOF scores were computed based on comparisons between model-predicted outcomes and calibration targets. Using 50 randomly resampled, good-fitting parameter sets, we assessed the external consistency and face validity of the model, comparing predicted screening outcomes to independent data. To illustrate the advantage of this approach in reflecting parameter uncertainty, we used the 50 sets to project the distribution of health outcomes in U.S. women under different cervical cancer prevention strategies. Results Approximately 200 good-fitting parameter sets were identified from 1,000,000 simulated sets. Modeled screening outcomes were externally consistent with results from multiple independent data sources. Based on 50 good-fitting parameter sets, the expected reductions in lifetime risk of cancer with annual or biennial screening were 76% (range across 50 sets: 69–82% and 69% (60–77%, respectively. The reduction from vaccination alone was 75%, although it ranged from 60% to 88%, reflecting considerable parameter
Goldhaber-Fiebert, Jeremy D; Stout, Natasha K; Ortendahl, Jesse; Kuntz, Karen M; Goldie, Sue J; Salomon, Joshua A
To provide quantitative insight into current U.S. policy choices for cervical cancer prevention, we developed a model of human papillomavirus (HPV) and cervical cancer, explicitly incorporating uncertainty about the natural history of disease. We developed a stochastic microsimulation of cervical cancer that distinguishes different HPV types by their incidence, clearance, persistence, and progression. Input parameter sets were sampled randomly from uniform distributions, and simulations undertaken with each set. Through systematic reviews and formal data synthesis, we established multiple epidemiologic targets for model calibration, including age-specific prevalence of HPV by type, age-specific prevalence of cervical intraepithelial neoplasia (CIN), HPV type distribution within CIN and cancer, and age-specific cancer incidence. For each set of sampled input parameters, likelihood-based goodness-of-fit (GOF) scores were computed based on comparisons between model-predicted outcomes and calibration targets. Using 50 randomly resampled, good-fitting parameter sets, we assessed the external consistency and face validity of the model, comparing predicted screening outcomes to independent data. To illustrate the advantage of this approach in reflecting parameter uncertainty, we used the 50 sets to project the distribution of health outcomes in U.S. women under different cervical cancer prevention strategies. Approximately 200 good-fitting parameter sets were identified from 1,000,000 simulated sets. Modeled screening outcomes were externally consistent with results from multiple independent data sources. Based on 50 good-fitting parameter sets, the expected reductions in lifetime risk of cancer with annual or biennial screening were 76% (range across 50 sets: 69-82%) and 69% (60-77%), respectively. The reduction from vaccination alone was 75%, although it ranged from 60% to 88%, reflecting considerable parameter uncertainty about the natural history of type-specific HPV
Fontecha, Nerea; Nieto, Maria Carmen; Andía, Daniel; Cisterna, Ramón; Basaras, Miren
Human papillomavirus (HPV) DNA testing plays a main role in the management of cervical cancer, however to improve the specificity in cervical screening, there is a need to develop and validate different approaches that can identify women at risk for progressive disease. Nowadays, mRNA expression of viral E6 and E7 HPV oncogenes stands up as a potential biomarker to improve cervical screening. We aimed to validate a method for RNA extraction, detect HPV mRNA expression and, assess the relationship between E6/E7 mRNA expression and pathology of patients' lesions and progression. This study included 50 specimens that had been previously genotyped as HPV16, 18, 31, 33 and/or 45. Cervical swabs were extracted with three different RNA extraction methods -Nuclisens manual extraction kit (bioMérieux), High Pure Viral RNA Kit (Roche) and RNeasy Plus Mini kit (Qiagen)-, and mRNA was detected with NucliSens EasyQ HPV version 1 test (bioMérieux) afterwards. Association of oncogene expression with pathology and lesion progression was analyzed for each extraction method. E6/E7 mRNA positivity rate was higher in samples analyzed with bioMérieux (62%), followed by Roche (24%) and Qiagen (6%). Women with lesions and lesion progression showed a higher prevalence of viral RNA expression than women that had not lesions or with lesion persistence. While bioMérieux revealed a higher sensitivity (77.27%), Roche presented a higher PPV (75%) and an increased specificity (89.28%). Extraction methods based on magnetic beads provided better RNA yield than those based in columns. Both Nuclisens manual extraction kit (bioMérieux) and High Pure Viral RNA Kit (Roche) seemed to be adequate for E6/E7 mRNA detection. However, none of them revealed both high sensitivity and specificity values. Further studies are needed to obtain and validate a standard gold method for RNA expression detection, to be included as part of the routine cervical screening program.
Levi, Angelique W; Bernstein, Jane I; Hui, Pei; Duch, Kara; Schofield, Kevin; Chhieng, David C
All Food and Drug Administration-approved methods in the United States for human papillomavirus testing including the Hybrid Capture 2 human papillomavirus assay and the Roche cobas human papillomavirus test are approved for cytology specimens collected into ThinPrep media but not for specimens collected into SurePath solution. To compare the performance of the Roche cobas and Hybrid Capture 2 tests for the detection of high-risk human papillomavirus using both ThinPrep and SurePath preparations as part of a validation study. One thousand three hundred seventy-one liquid-based cytology samples, including 1122 SurePath and 249 ThinPrep specimens, were tested for high-risk human papillomavirus DNA using the Roche cobas human papillomavirus test and the Hybrid Capture 2 human papillomavirus assay. For cases with discrepant results, confirmatory testing was performed using Linear Array human papillomavirus testing. One hundred and fifty-six (11.38%) and 184 (13.42%) of the 1371 specimens tested positive for high-risk human papillomavirus DNA using the Hybrid Capture 2 human papillomavirus assay and Roche cobas human papillomavirus assay, respectively. In addition, 1289 (94.0%) of 1371 specimens demonstrated concordant high-risk human papillomavirus results with a κ value of 0.72 (95% confidence interval, 065-0.78). There was no statistically significant difference in the percentage of positive high-risk human papillomavirus results between the 2 liquid-based preparations with either assay. Discordant results between the 2 assays were noted in 82 of 1371 cases (6%). Twenty-seven of 82 cases (32.9%) were Hybrid Capture 2 positive/Roche cobas negative and 55 of 82 cases (67.1%) were Roche cobas positive/Hybrid Capture 2 negative. Two of 20 Hybrid Capture 2-positive/Roche cobas-negative cases (10%) and 26 of 37 Roche cobas-positive/Hybrid Capture 2-negative cases (70%) tested positive for high-risk human papillomavirus by Linear Array. Both assays showed good agreement
Vanya, Melinda; Jakó, Mária; Terhes, Gabriella; Szakács, László; Kaiser, László; Deák, Judit; Bártfai, György
Although the natural history of cervical and oral human papillomavirus infection has been intensively investigated in the past years, the ability of this virus to infect oral and genital mucosae in the same individual and its potential to co-infect both cervical and oral mucosa are still unclear. The aim of the authors was to assess the presence of oropharyngeal human papillomavirus infection in women with cervical lesions in the South-Eastern Hungarian population. The total of 103 women have been included in the study between March 1, 2013 and January 1, 2015. Brushing was used to collect cells from the oropharyngeal mucosa. Human papillomavirus DNA was detected using polymerase chain reaction, and Amplicor line blot test was used for genotyping. Oropharyngeal human papillomavirus infection was detected in 2 cases (3%). The detected genotypes were 31, 40/61 and 73 in the oropharyngeal region. The results indicate that in women with cervical lesions oropharyngeal human papillomavirus infection rarely occurs.
Herd, Karen A; Harvey, Tracey; Khromykh, Alexander A; Tindle, Robert W
The persistence of the E7 oncoprotein in transformed cells in human papillomavirus (HPV)-associated cervical cancer provides a tumour-specific antigen to which immunotherapeutic strategies may be directed. Self-replicating RNA (replicon) vaccine vectors derived from the flavivirus Kunjin (KUN) have recently been reported to induce T-cell immunity. Here, we report that inclusion of a CTL epitope of HPV16 E7 protein into a polyepitope encoded by a KUN vector induced E7-directed T-cell responses and protected mice against challenge with an E7-expressing epithelial tumour. We found replicon RNA packaged into virus-like particles to be more effective than naked replicon RNA or plasmid DNA constructed to allow replicon RNA transcription in vivo. Protective immunity was induced although the E7 CTL epitope was subdominant in the context of other CTL epitopes in the polyepitope. The results demonstrate the efficacy of the KUN replicon vector system for inducing protective immunity directed towards a virally encoded human tumour-specific antigen, and for inducing multi-epitopic CTL responses.
Gisele R de Oliveira
Full Text Available BACKGROUND Increasing evidence suggests that human papillomavirus (HPV intratype variants (specific lineages and sublineages are associated with pathogenesis and progression from HPV infection to persistence and the development of cervical cancer. OBJECTIVES This study aimed to verify the prevalence of HPV infection and distribution of HPV types and HPV16 variants in southern Brazil in women with normal cytology or intraepithelial lesions. METHODS HPV typing was determined by L1 gene sequencing. To identify HPV16 variants, the LCR and E6 regions were sequenced, and characteristic single nucleotide variants were identified. FINDINGS A total of 445 samples were studied, with 355 from cervical scrapes and 90 from cervical biopsies. HPV was detected in 24% and 91% of these samples, respectively. The most prevalent HPV types observed were 16 (cervical, 24%; biopsies, 57% and 58 (cervical, 12%; biopsies, 12%. Seventy-five percent of the HPV16-positive samples were classified into lineages, with 88% defined as lineage A, 10% as lineage D, and 2% as lineage B. MAIN CONCLUSIONS This study identified a high frequency of European and North American HPV16 lineages, consistent with the genetic background of the human population in southern Brazil.
Jeronimo, Jose; Bansil, Pooja; Valdez, Melissa; Kang, Le-Ni; Zhao, Fang-Hui; Qiao, You-Lin; Chen, Wen; Zhang, Xun; Paul, Proma; Bai, Ping; Peck, Roger; Li, Jing; Chen, Feng; Stoler, Mark H; Castle, Philip E
To examine the influence of human papillomavirus (HPV) genotypes on the sensitivity of visual inspection with acetic acid (VIA) for screening, and colposcopy for diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+). Women aged 25 to 65 years from China (n = 7,541) were screened with 6 tests (careHPV and Hybrid Capture 2 on self- and clinician-collected specimens; HPV-16, HPV-18, HPV-45 E6 detection; and VIA). Biopsies from women with a diagnosis of CIN2+ underwent testing for 25 HPV genotypes using SPF10/LiPA. Human papillomavirus genotyping results were classified according to broad categories of cancer risk. Among the 143 women with a diagnosis of CIN2+, the percentage who were HPV16 positive increased with increasing severity of diagnosis: 33.3% for CIN2 (n = 39), 69.1% for CIN3 (n = 94), and 90% for cancer (n = 10). There was a higher percentage of HPV-16 in women with abnormal colposcopic impression (p = .007) and positive VIA (p = .02) than normal colposcopy and negative VIA, respectively. Colposcopy and VIA were more sensitive to detect CIN2+ among HPV-16- and/or HPV-18-positive women than HPV-16-/HPV-18-negative women (67.4% vs 43.1%, p = .008, for colposcopy; and 53.3% vs 37.3%, p = .08, for VIA). Human papillomavirus type 16 is related to more clear visual acetowhite changes in the epithelium. Therefore, we should expect a reduction of the performance of VIA for cervical cancer screening to identify women with CIN2+, and reduction of the performance of colposcopy to diagnose CIN2+, in vaccinated populations.
Omrani-Navai, Versa; Alizadeh-Navaei, Reza; Yahyapour, Yousef; Hedayatizadeh-Omran, Akbar; Abediankenari, Saeid; Janbabaei, Ghasem; Toghani, Fatima
Gastrointestinal (GI) malignancies are the most common cancers and account for nearly half of all cancer-related deaths in Iran. There was a strong association between human papillomavirus (HPV) infection and urogenital cancers, in particular the cervix. However, there is no clear causal relationship in all types of cancers, including gastrointestinal cancers. Therefore, the present study as a systematic review and meta-analysis was designed to evaluate the prevalence and relation of HPV in GI cancers. This systematic review and meta-analysis study assess the prevalence of human papillomavirus in GI cancers in Iran. Data were collected by searching electronic databases, including PubMed, Google Scholar, Scopus, SID and Iranmedex by English and Persian key words up to August 2016. Key words included: Human Papillomavirus, HPV, Cancer, Neoplasm, Carcinoma, Esophageal, colorectal, Gastrointestinal and Iran articles were entered in the EndNote software and duplicate papers were excluded. Data were extracted and analyzed by comprehensive meta-analysis software, Version 2 (CMA.V2) and random effects model. Finally, we included 17 studies in this meta-analysis. The prevalence of HPV in Iranian patients with GI cancers was 16.4% (CI95%: 10.4-24.9). Considering all HPV types, the odds ratio of GI cancers in positive patients was 3.03 (CI95%: 1.42-6.45) while in patients with HPV-16 was 3.62 (CI: 1.43-4.82). The results show a strong relationship between HPV infection especially high-risk HPV type 16 and GI cancers in Iranian population.
Videla, Sebastian; Darwich, Laila; Cañadas, Maria Paz; Paredes, Roger; Tarrats, Antoni; Castella, Eva; Llatjos, Mariona; Bofill, Margarita; Clotet, Bonaventura; Sirera, Guillem
To study the epidemiology of different human papillomavirus (HPV) genotypes in cervical samples of HIV-1-infected women with normal Papanicolau smears. : Retrospective analysis of a prospective cohort. We selected HIV-1-infected women with 2 consecutive normal Papanicolau smears at baseline and at least 1 baseline and 1 follow-up cervical sample. HPV infection was assessed by second-generation hybrid capture (HC-2) and multiplex polymerase chain reaction (mPCR). HPV genotypes were determined by mPCR. From a cohort of 139 women followed up to 4 years, 93 women meeting the inclusion criteria were analyzed. The mean period between samples was 20 months (range, 6-44 months). HPV baseline prevalence was 63% [59/93; 95% confidence interval (CI), 53% to 73%] using polymerase chain reaction and 41% (38/93; 95% CI, 31% to 51%) using HC-2, P = 0.007 (kappa, 0.45; P = 0.001). The most prevalent high oncogenic risk genotypes (HR-HPV) were HPV-16 (28%), HPV-33 (18%), HPV-52 (12%), HPV-58 (11%), and HPV-39 (11%). Infection with multiple HPV genotypes was detected in >40% of women. HPV infection persisted at follow-up in 86% (51/59; 95% CI, 77% to 95%) by polymerase chain reaction and 76% (29/38; 95% CI, 62% to 90%) by HC-2. HPV infection persisted in 55% of women with samples available beyond 3 years. The actuarial probabilities of clearance and incidence of HPV infection at 36 months were 16% and 45%, respectively. HPV infection is highly prevalent and persistent among HIV-1-infected women with normal Papanicolau smears. HR-HPV genotypes other than HPV-16 (HPV-33, HPV-52) are frequently detected in HIV-infected women. mPCR provides better surveillance of HPV infection than HC-2 methods.
Lai, Y M; Yang, F P; Pao, C C
To investigate the possible presence and expression of human papillomavirus viruses (HPV) in human plasma and sperm cells. Controlled clinical study. A major medical center affiliated with a medical college. Twenty-four randomly selected patients who attended Fertility Clinics at the Chang Gung Memorial Hospital. Specimens of semen were collected from volunteered patients The presence of HPV types 16 and 18 DNA and RNA sequences were examined by polymerase chain reaction. Human papillomavirus type 16 E6 and E7 DNA and RNA sequences were found in two and zero seminal plasma specimens, respectively, and in six and two sperm cells specimens, respectively. Deoxyribonucleic acid and RNA sequences of HPV type 18 were found in eight and two seminal specimens and in 11 and 5 sperm cells specimens, respectively. These results seem to suggest that HPV cannot only infect human sperm cells, certain HPV genes are expressed actively in infected sperm cells. The virus-infected sperm cells conceivably can behave as vectors or carriers for the transmission of HPV, to sexual partner during sexual contact, to fetuses through fertilized eggs, or both.
Preisler, Sarah Nørgaard; Rebolj, Matejka; Ejegod, Ditte Møller
Background High-risk Human Papillomavirus (HPV) testing is replacing cytology in cervical cancer screening as it is more sensitive for preinvasive cervical lesions. However, the bottleneck of HPV testing is the many false positive test results (positive tests without cervical lesions). Here, we...... evaluated to what extent these can be explained by cross-reactivity, i.e. positive test results without evidence of high-risk HPV genotypes. The patterns of cross-reactivity have been thoroughly studied for hybrid capture II (HC2) but not yet for newer HPV assays although the manufacturers claimed...
Levi, José E.; Fink, Maria C.S.; Canto, Cynthia L.M.; Carretiero, Nadily; Matsubara, Regina; Linhares, Iara; Dores, Gérson B. das; Castelo, Adauto; Segurado, Aluísio; Uip, David E.; Eluf Neto, José
HIV-infected women from São Paulo city were enrolled in a cross-sectional study on Human Papillomavirus (HPV) and cervical intraepithelial neoplasia (CIN) prevalence and their association with laboratory markers of AIDS, namely HIV viral load and CD4+ cell counts. A cervical specimen was collected and submitted to Hybrid Capture, a test for HPV viral load determination. HPV-DNA was detected in 173 of 265 women (64.5%). Twenty (7.5%) women were infected by one or more low-risk viruses, 89 (33%...
Kocjan, Boštjan; Poljak, Mario; Oštrbenk, Anja
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...
Yat Ming Lau; Tak Hong Cheung; Winnie Yeo; Frankie Mo; Mei Yung Yu; Kun Min Lee; Ho, Wendy C. S.; Yeung, Apple C. M.; Priscilla T. Y. Law; Chan, Paul K. S.
High-risk human papillomavirus (HPV) types are associated with cervical cancer. It is well established that individual HPV types vary in oncogenicity, but current data on their prognostic implication remain controversial. We examined the association between HPV types/species and the survival of 236 Chinese women aged 26-87 (mean 54.4) years after receiving primary treatment for cervical cancer. Overall, 45.8% were of FIGO stage I, 41.9% stage II, and 12.3% stage III. The four most prevalent t...
Gollust, Sarah E; Dempsey, Amanda F; Lantz, Paula M; Ubel, Peter A; Fowler, Erika Franklin
State actions requiring adolescent girls to receive the human papillomavirus (HPV) vaccine created controversy following the vaccine's approval in 2006. Some health professionals worried that the controversy might dampen public support for those state policies and for other school immunizations in general. We fielded an experimental Internet survey to determine how controversy affects attitudes about vaccines. We discovered that public support for the HPV vaccine mandates wanes when the public is informed that the policies are controversial. However, the experimental survey also revealed that exposure to this policy controversy did not spill over and reduce public support for immunizations in general.
Chin’ombe, Nyasha; Sebata, Natasha L; Ruhanya, Vurayai; Matarira, Hilda T
Cervical cancer is one of the major causes of morbidity and mortality in women in Zimbabwe. This is mainly due to the high prevalence of high-risk human papillomavirus (HPV) genotypes in the population. So far, few studies have been done that showed the presence of high-risk genital HPV genotypes such as 16, 18, 31, 33, 52, 58 and 70 in Zimbabwean women with cervical cancer. The prevalence of HPV DNA in women with cervical cancer has been shown to range from 63% to 98%. The high-risk HPV 16, ...
Soto-De Leon, S C; Camargo, M; Sanchez, R; Leon, S; Urquiza, M; Acosta, J; Monsalve, D; Rodriguez, L E; Patarroyo, M E; Patarroyo, M A
The prevalence of human papillomavirus (HPV) infections in 2109 females inhabiting five cities of Colombia was determined. Of the 49.2% with an HPV infection, 59.8% were infected with more than one viral type. Species 7 (of the the genus Alphapapillomavirus) was associated with multiple infections. Analysis of the socio-demographic data revealed a statistically significant protective effect associated with the status of civil union (civil recognition of cohabitation without marriage), and indigenous ethnicity proved to be a risk factor for HPV infection. This is the first study comparing HPV infection among women from geographical regions of Colombia with different socio-cultural structures.
Aleshire, Mollie E; Lock, Sharon E; Jensen, Lynne A
The incidence of human papillomavirus (HPV) is higher in college students than in many other populations. HPV puts young women at risk for developing cervical cancer. The relationship between HPV and risky sexual behaviors has been well established. This study describes female college students' knowledge regarding HPV and cervical cancer, identifies sexual risk behaviors in this group, and assesses whether there is any relationship between knowledge of HPV and cervical cancer and the sexual risk behaviors in this population. Health care providers need to be aware of this health issue and actively promote appropriate prevention strategies. Copyright © 2013 Elsevier Inc. All rights reserved.
Objective To measure knowledge and awareness of human papillomavirus (HPV) testing in the USA, the UK and Australia. Methods Participants in the USA, UK and Australia completed an anonymous web-based survey measuring awareness and knowledge of HPV (n=2409). We report analyses on a subsample of 1473 men and women in the USA (n=617), UK (n=404) and Australia (n=452) who had heard of HPV and completed questions about HPV testing. Results Overall, 50% of the sample (742/1473) had heard of HPV tes...
Ambühl, Lea Maria Margareta; Baandrup, Ulrik; Dybkær, Karen
Based on the current literature, we aimed to provide an overview on Human Papillomavirus prevalence in normal pregnancies and pregnancies with adverse outcome.We conducted a systematic literature search in PubMed and Embase. Data extracted from the articles and used for analysis included HPV...... delivery, and the presence of HPV in both the cervix and the placenta. However, a reliable conclusion is difficult to draw due to the limited number of studies conducted on material from pregnancies with adverse outcome and the risk of residual confounding....
Cramon, Cecilie; Lindegaard Poulsen, Christina; Hartling, Ulla Birgitte
and laboratory tests. RESULTS: The study comprised 200 patients. The median age at referral was 22 (interquartile range (IQR): 19.5-26) years, and age at first vaccination was 14 (IQR: 12-21) years. The most common symptoms were headache (93%), fatigue/tiredness (93%) and dizziness when standing up (90......INTRODUCTION: Since the introduction of the quadrivalent human papillomavirus vaccine, young girls and women have reported a broad range of symptoms. These have been described as possible adverse effects of the vaccine. In this study, we describe demographic characteristics, symptomatology...... associated with the vaccine. FUNDING: none. TRIAL REGISTRATION: not relevant....
Human papillomavirus (HPV) infection has been thoroughly demonstrated as a major factor in the pathogenesis of cervical cancer, but HPV's role in penile cancer has not been demonstrated as convincingly. The author reviews several major investigations from the past 35 years and finds that men with certain risk factors (eg, intact foreskin, history of sexual encounters outside marriage, and history of first intercourse at a younger age) place their current female sex partners at greater risk for cervical carcinoma caused by transmission of HPV infection. A brief description of HPV prevention and treatment options is also provided.
Fontecha, Nerea; Nieto, Maria Carmen; And?a, Daniel; Cisterna, Ram?n; Basaras, Miren
Background Human papillomavirus (HPV) DNA testing plays a main role in the management of cervical cancer, however to improve the specificity in cervical screening, there is a need to develop and validate different approaches that can identify women at risk for progressive disease. Nowadays, mRNA expression of viral E6 and E7 HPV oncogenes stands up as a potential biomarker to improve cervical screening. We aimed to validate a method for RNA extraction, detect HPV mRNA expression and, assess t...
Vasiljevic, Natasa; Hazard, Kristina; Eliasson, Linda
Two novel human papillomaviruses (HPVs), HPV93 and HPV96, with genomes of 7450 and 7438 bp, respectively, are described. The L1 open reading frame of HPV93 showed highest identity to HPV24 (79%) and that of HPV96 had highest identity to HPV92 (71%). Real-time PCR for HPV92, 93 and 96 on stripped ...... per 45 cells to one copy per 10,000 cells. The E7 proteins of HPV92, 93 and 96 were found to bind the retinoblastoma protein (pRb). These results suggest a possible role for these HPV types in skin carcinogenesis that deserves further study....
Perino, Antonio; Giovannelli, Lucia; Schillaci, Rosaria; Ruvolo, Giovanni; Fiorentino, Francesco Paolo; Alimondi, Pietro; Cefalù, Eleonora; Ammatuna, Piero
A prospective study was performed to assess the relationship between human papillomavirus (HPV) infection in 199 infertile couples and outcome of assisted reproductive technologies (ARTs). A highly statistically significant correlation between pregnancy loss rate (proportion of pregnancies detected by β-hCG that did not progress beyond 20 weeks) and positive HPV DNA testing in the male partner of infertile couples, compared with HPV negatives, was observed (66.7% vs. 15%). Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
Forslund, Ola; Ly, Hoang; Higgins, Geoff
A single tube nested 'hanging droplet' PCR was developed for detection of cutaneous human papillomavirus (HPV) DNA of the phylogenetic group B1. The nested PCR was compared with a single round PCR method by testing 56 fresh biopsies from Australian skin tumour patients. HPV DNA was detected in 64% (36/56) of the biopsies by nested PCR and in 30% (17/56) by single round PCR (Pspectrum of HPV types from skin tumours, but further improvements are needed before all HPV infections in skin can be detected by a single assay.
Monitoring and ordering practices for human papillomavirus in cervical cytology: findings from the College of American Pathologists Gynecologic Cytopathology Quality Consensus Conference working group 5.
Booth, Christine N; Bashleben, Christine; Filomena, Carol A; Means, Marilee M; Wasserman, Patricia G; Souers, Rhona J; Henry, Michael R
The association of certain types of human papillomavirus with cervical carcinoma is well established. Human papillomavirus testing is now routinely used to screen for cervical carcinoma and precursor lesions of the cervix (cotesting and reflex testing) and these results are considered in patient triage and management. To provide information about current laboratory practices in human papillomavirus testing and consensus best practice statements based on results from the College of American Pathologists' laboratory-based survey funded by the Centers for Disease Control and Prevention. The College of American Pathologists submitted a paper-based survey to 1245 laboratories in the United States. After review of the initial results, follow-up Web-based survey results, and a literature review by an expert working group, consensus best practice statements were constructed by working group members for presentation at a national consensus conference. These best practice statements were discussed and then voted upon by conference participants. A total of 525 laboratories responded to survey questions about human papillomavirus ordering and monitoring practices, whereas 546 responded to the overall survey. In most laboratories (87.6%), the high-risk human papillomavirus test is ordered as a reflex test by providers. A minority of laboratories (11.9%) routinely bundle low- and high-risk human papillomavirus tests. Most laboratories (84.4%) do not limit testing in patients with atypical squamous cells to women older than 20 years. More than half of laboratories (53.3%) monitor human papillomavirus positive rates in Papanicolaou tests with atypical squamous cells of undetermined significance. It is not appropriate for laboratories to offer low-risk human papillomavirus testing for any clinical circumstance in gynecologic cytology. Laboratories should not order human papillomavirus testing to resolve diagnostic discrepancies. It is a valuable broad measure of laboratory quality
Full Text Available OBJECTIVE: To identify the prevalence and factors associated with cervical human papillomavirus infection in women with systemic lupus erythematosus METHODS: This cross-sectional study collected traditional and systemic lupus erythematosus-related disease risk factors, including conventional and biologic therapies. A gynecological evaluation and cervical cytology screen were performed. Human papillomavirus detection and genotyping were undertaken by PCR and linear array assay. RESULTS: A total of 148 patients were included, with a mean age and disease duration of 42.5±11.8 years and 9.7±5.3 years, respectively. The prevalence of squamous intraepithelial lesions was 6.8%. The prevalence of human papillomavirus infection was 29%, with human papillomavirus subtype 59 being the most frequent. Patients with human papillomavirus were younger than those without the infection (38.2±11.2 vs. 44.2±11.5 years, respectively; p = 0.05, and patients with the virus had higher daily prednisone doses (12.8±6.8 vs. 9.7±6.7 mg, respectively; p = 0.01 and cumulative glucocorticoid doses (14.2±9.8 vs. 9.7±7.3 g, respectively; p = 0.005 compared with patients without. Patients with human papillomavirus infection more frequently received rituximab than those without (20.9% vs. 8.5%, respectively; p = 0.03. In the multivariate analysis, only the cumulative glucocorticoid dose was associated with human papillomavirus infection. CONCLUSIONS: The cumulative glucocorticoid dose may increase the risk of human papillomavirus infection. Although rituximab administration was more frequent in patients with human papillomavirus infection, no association was found. Screening for human papillomavirus infection is recommended in women with systemic lupus erythematosus.
Thomsen, Louise T; Frederiksen, Kirsten; Munk, Christian
OBJECTIVE: To determine the absolute risk of cervical intraepithelial neoplasia (CIN) grade 3 or cervical cancer (CIN 3 or worse) after detection of low-risk human papillomavirus (HPV) and after a negative high-risk HPV test. METHODS: In this prospective cohort study, consecutive liquid-based cer......OBJECTIVE: To determine the absolute risk of cervical intraepithelial neoplasia (CIN) grade 3 or cervical cancer (CIN 3 or worse) after detection of low-risk human papillomavirus (HPV) and after a negative high-risk HPV test. METHODS: In this prospective cohort study, consecutive liquid...
Pagliusi, Sonia R; Teresa Aguado, M
Last year, the World Health Organization (WHO) convened a gathering of experts, including scientists, national regulatory authorities, industry representatives, epidemiologists and government officials from both developed and developing countries to discuss appropriate endpoint measurements for HPV vaccine efficacy and effectiveness trials. The consultation also considered the regulatory requirements and public health issues that vaccine candidates should address before deployment, particularly in developing countries. This report summarizes the discussions and the conclusions reached over the course of the consultation. The general consensus of the consultation was that it would be desirable to have a globally-agreed, measurable efficacy endpoint for considering deployment of HPV vaccines in public health settings. After hearing from experts about virological and clinical endpoints to be considered, requirements of regulatory authorities of various countries and endpoints used to measure efficacy and effectiveness for another known cancer vaccine (hepatitis B), the experts agreed that ethical and time considerations make it necessary to use a surrogate endpoint, and not invasive cervical cancer, to define efficacy of HPV vaccines. While regulatory authorities of each country ultimately will determine the endpoints required for licensure, the consultation recommended that the endpoint for efficacy in population-based studies be, based on current knowledge, histologically-classified cervical intraepithelial neoplasias (CIN) of moderate or high-grade, as well as cancer. Since persistent infection with the same high-risk type is considered a predictor for moderate or high-grade cervical dysplasias and cancer, they might represent a useful endpoint in future vaccine efficacy studies. Indeed, if vaccines prove to be effective against transient or persistent HPV infections, it is likely that they will protect women against cervical cancer. The consultation recognized
Munoz, Marina; Camargo, Milena; Soto-De Leon, Sara C; Sanchez, Ricardo; Parra, Diana; Pineda, Andrea C; Sussmann, Otto; Perez-Prados, Antonio; Patarroyo, Manuel E; Patarroyo, Manuel A
Infection, coinfection and type-specific human papillomavirus (HPV) distribution was evaluated in human immunodeficiency virus (HIV)-positive women from paired cervical and urine samples. Paired cervical and urine samples (n = 204) were taken from HIV-positive women for identifying HPV-DNA presence by using polymerase chain reaction (PCR) with three generic primer sets (GP5+/6+, MY09/11 and pU1M/2R). HPV-positive samples were typed for six high-risk HPV (HR-HPV) (HPV-16, -18, -31, -33, -45 and -58) and two low-risk (LR-HPV) (HPV-6/11) types. Agreement between paired sample results and diagnostic performance was evaluated. HPV infection prevalence was 70.6% in cervical and 63.2% in urine samples. HPV-16 was the most prevalent HPV type in both types of sample (66.7% in cervical samples and 62.0% in urine) followed by HPV-31(47.2%) in cervical samples and HPV-58 (35.7%) in urine samples. There was 55.4% coinfection (infection by more than one type of HPV) in cervical samples and 40.2% in urine samples. Abnormal Papanicolau smears were observed in 25.3% of the women, presenting significant association with HPV-DNA being identified in urine samples. There was poor agreement of cervical and urine sample results in generic and type-specific detection of HPV. Urine samples provided the best diagnosis when taking cytological findings as reference. In conclusion including urine samples could be a good strategy for ensuring adherence to screening programs aimed at reducing the impact of cervical cancer, since this sample is easy to obtain and showed good diagnostic performance.
Full Text Available Infection, coinfection and type-specific human papillomavirus (HPV distribution was evaluated in human immunodeficiency virus (HIV-positive women from paired cervical and urine samples. Paired cervical and urine samples (n = 204 were taken from HIV-positive women for identifying HPV-DNA presence by using polymerase chain reaction (PCR with three generic primer sets (GP5+/6+, MY09/11 and pU1M/2R. HPV-positive samples were typed for six high-risk HPV (HR-HPV (HPV-16, -18, -31, -33, -45 and -58 and two low-risk (LR-HPV (HPV-6/11 types. Agreement between paired sample results and diagnostic performance was evaluated. HPV infection prevalence was 70.6% in cervical and 63.2% in urine samples. HPV-16 was the most prevalent HPV type in both types of sample (66.7% in cervical samples and 62.0% in urine followed by HPV-31(47.2% in cervical samples and HPV-58 (35.7% in urine samples. There was 55.4% coinfection (infection by more than one type of HPV in cervical samples and 40.2% in urine samples. Abnormal Papanicolau smears were observed in 25.3% of the women, presenting significant association with HPV-DNA being identified in urine samples. There was poor agreement of cervical and urine sample results in generic and type-specific detection of HPV. Urine samples provided the best diagnosis when taking cytological findings as reference. In conclusion including urine samples could be a good strategy for ensuring adherence to screening programs aimed at reducing the impact of cervical cancer, since this sample is easy to obtain and showed good diagnostic performance.
Hernández-Valencia, Marcelino; Carrillo-Pacheco, Adia; Hernández-Quijano, Tomás; Zárate, Arturo
Human papilloma virus can infect any mucous of the body and can cause cancer of the uterine cervix. This suggests recommending the Papanicolaou smear combined with a test for detection of human papillomavirus with a frequency interval of 3 years, since it grants greater information and fidelity to the result. The detection studies should begin at the age of 21 years and should stop at 65 years age. Until recently specific treatments did not exist to treat human papilloma virus, but recently some drugs that have demonstrated good effectiveness in curing the infection of human papilloma virus. One example is glycirrhicinic acid, which has demonstrated fewer adverse effects, as well as the possibility that its systemic employment allows treatment of lesions that are difficult to approach. The medical recommendations should be in constant revision, since a clinical trial can modify the interpretation of what is necessary to individualize each patient's treatment.
Frederiksen, Hanne; Jensen, Tina Kold; Jørgensen, Niels
Several non-persistent industrial chemicals have shown endocrine disrupting effects in animal studies and are suspected to be involved in human reproductive disorders. Among the non-persistent chemicals that have been discussed intensively during the past years are phthalates, bisphenol A (BPA...
the anogenital tract and other mucosal areas of the human body. They are classified as high or low oncogenic risk according to their involvement in the genesis of benign or malignant lesions.[7,8] Among these, at least 15 are considered high‑risk. HPV (HR‑HPV) and are strongly associated with progression. Prevalence of ...
Cervical cancer remains an important public health problem in developing countries where over 80% of the global burden occurs annually but screening has been ineffective. In a polygamous country like Ghana with a high incidence of cervical cancer but no national screening program, the Human Papilloma Virus (HPV) ...
Hebnes, Julie B; Olesen, Tina B; Duun-Henriksen, Anne Katrine
contribute knowledge that may be useful as a baseline measure before the introduction of HPV vaccination for boys in Europe, and add to understanding of the epidemiology of HPV infection in men. Hebnes JB, Olesen TB, Duun-Henriksen AK, Munk C, Norrild B, and Kjaer SK. Prevalence of genital human...
Nonato, Dejan R; Alves, Rosane R F; Ribeiro, Andrea A; Saddi, Vera A; Segati, Kelly D; Almeida, Keila P; de Lima, Yanna A R; D'Alessandro, Walmirton B; Rabelo-Santos, Silvia H
Human papillomavirus and Chlamydia trachomatis share the same route of sexual transmission and possess similar risk factors, indicating that coinfection may act synergistically in the induction of epithelial cell abnormalities. This study aimed to determine the prevalence of human papillomavirus and Chlamydia trachomatis in adolescents and young women and identify factors associated with coinfection. This cross-sectional study included 276 female participants, aged 15-24 years, who were sexually active. Interviews were conducted and cervical specimens were collected for cervical smears and molecular tests. All cervical specimens were tested for 27 human papillomavirus genotypes by polymerase chain reaction amplification and hybridization to a human papillomavirus linear array. Detection of Chlamydia trachomatis was performed by polymerase chain reaction using primers directed to the region encoding the cryptic plasmid. Bivariate and multivariate analyses were performed to evaluate the factors associated with coinfection with human papillomavirus and Chlamydia trachomatis. The odds ratio, the adjusted odds ratio, and the 95% confidence interval were calculated. The prevalence of infection by Chlamydia trachomatis and human papillomavirus was 9.1% (95% confidence interval, 5.61-12.4) and 47.1% (95% confidence interval, 41.0-53.2), respectively. The prevalence of coinfection with human papillomavirus and Chlamydia trachomatis was 5.8% (95% confidence interval, 3.3-9.2); coinfection with 1 human papillomavirus type was 3.3% (95% confidence interval, 1.5-6.1) and with multiple types was 2.5% (95% confidence interval, 1.0-5.2). The prevalence of cytological abnormalities was 12.3% (95% confidence interval, 8.6-16.79). Human papillomavirus infections of high oncogenic risk were more prevalent (85.4%). Factors independently associated with coinfection of human papillomavirus/Chlamydia trachomatis obtained by multivariate analysis were the initiation of sexual activity
Wu, L; Goodwin, E C; Naeger, L K
Expression of the bovine papillomavirus E2 protein in cervical carcinoma cells represses expression of integrated human papillomavirus (HPV) E6/E7 oncogenes, followed by repression of the cdc25A gene and other cellular genes required for cell cycle progression, resulting in dramatic growth arrest...
Zhao, Nan; Huh, Jimi; Murphy, Sheila T.; Chatterjee, Joyee S.; Baezconde-Garbanati, Lourdes
Korean Americans represent one of the fastest growing Asian subpopulations in the United States. Despite a dramatic reduction in incidence nationwide, cervical cancer remains a major threat for Korean American women. By preventing the strains of the Human Papillomavirus (HPV) known to cause cervical cancer, the HPV vaccines appear to be a promising solution to reduce the persistent disparities in cervical cancer among not only Korean Americans, but also other racial and ethnic minorities more generally. However, current literature lacks a better understanding of how cultural and behavioral factors influence Korean American women’s intention to vaccinate their adolescent daughters against HPV. This manuscript presents the results of testing the mechanisms through which interdependent self-construal (an orientation of self in which individuals define themselves primarily through their relationships with others), attitudes, and subjective norms impact Korean American mothers’ intention to vaccinate their daughters. Our findings suggest that self-construal holds promise for health communication research to not only uncover the rich variance of health-related beliefs among individuals of shared cultural descent, but also to understand the context in which these beliefs are embedded. PMID:25558309
Caberg, Jean-Hubert D; Hubert, Pascale M; Begon, Dominique Y; Herfs, Michael F; Roncarati, Patrick J; Boniver, Jacques J; Delvenne, Philippe O
Human papillomavirus (HPV) infection, particularly type 16, is causally associated with cancer of the uterine cervix. The persistence or progression of cervical lesions suggests that viral antigens are not adequately presented to the immune system. This hypothesis is reinforced by the observation that most squamous intra-epithelial lesions show quantitative and functional alterations of Langerhans cells (LCs). Moreover, E-cadherin-dependent adhesion of LC to keratinocytes (KCs) is defective in cervical HPV16-associated (pre)neoplastic lesions. The possible role of viral oncoprotein E7 in the reduced levels of cell surface E-cadherin was investigated by silencing HPV16 E7 by RNA interference (siRNA). This treatment induced an increased cell surface E-cadherin expression in HPV16-positive KC and a significant adhesion of LC to these squamous cells. The E-cadherin re-expression following HPV16 E7 silencing was associated with increased detection levels of retinoblastoma protein and the activating protein (AP)-2alpha transcription factor. These data suggest that HPV16 E7-induced alterations of LC/KC adhesion may play a role in the defective immune response during cervical carcinogenesis.
Clarke Megan A
Full Text Available Abstract Background Vaginal pH is related to genital tract inflammation and changes in the bacterial flora, both suggested cofactors for persistence of human papillomavirus (HPV infection. To evaluate the relationship between vaginal pH and HPV, we analyzed data from our large population-based study in Guanacaste, Costa Rica. We examined vaginal pH and the risk of HPV infection, cytological abnormalities, and C. trachomatis infection. Methods Our study included 9,165 women aged 18-97 at enrollment with a total of 28,915 visits (mean length of follow-up = 3.4 years. Generalized estimating equations were used to evaluate the relationship between vaginal pH and HPV infection (both overall and single versus multiple types and low-grade squamous intraepithelial lesions (LSIL, the cytomorphic manifestation of HPV infection. The relationship between enrollment vaginal pH and C. trachomatis infection was assessed by logistic regression. Results were stratified by age at visit. Results Detection of HPV was positively associated with vaginal pH, mainly in women C. trachomatis DNA was associated with increased vaginal pH in women Conclusions Our findings suggest a possible association of the cervical microenvironment as a modifier of HPV natural history in the development of cervical precancer and cancer. Future research should include studies of vaginal pH in a more complex assessment of hormonal changes and the cervicovaginal microbiome as they relate to the natural history of cervical neoplasia.
Full Text Available Background. Haitian immigrant women residing in Little Haiti, a large ethnic enclave in Miami-Dade County, experience the highest cervical cancer incidence rates in South Florida. While this disparity primarily reflects lack of access to screening with cervical cytology, the burden of human papillomavirus (HPV which causes virtually all cases of cervical cancer worldwide, varies by population and may contribute to excess rate of disease. Our study examined the prevalence of oncogenic and nononcogenic HPV types and risk factors for HPV infection in Little Haiti. Methods. As part of an ongoing community-based participatory research initiative, community health workers recruited study participants between 2007 and 2008, instructed women on self-collecting cervicovaginal specimens, and collected sociodemographic and healthcare access data. Results. Of the 242 women who contributed adequate specimens, the overall prevalence of HPV was 20.7%, with oncogenic HPV infections (13.2% of women outnumbering nononcogenic infections (7.4%. Age-specific prevalence of oncogenic HPV was highest in women 18–30 years (38.9% although the prevalence of oncogenic HPV does not appear to be elevated relative to the general U.S. population. The high prevalence of oncogenic types in women over 60 years may indicate a substantial number of persistent infections at high risk of progression to precancer.
Shvetsov, Yurii B.; Hernandez, Brenda Y.; Wilkens, Lynne R.; Thompson, Pamela J.; Franke, Adrian A.; Zhu, Xuemei; Goodman, Marc T.
Anal human papillomavirus (HPV) infection is common among women and the cause of most anal malignancies. The incidence of anal cancer has been increasing among U.S. women; yet few co-factors for the natural history of anal HPV infection have been identified. We examined the hypothesis that plasma carotenoid, retinol, and tocopherol concentrations are associated with the acquisition and clearance of anal HPV infection in a cohort of 279 Hawaiian residents followed at 4-month intervals for a mean duration of 16 months. At each visit, interviews were conducted and biological specimens were obtained, including anal cell specimens for HPV DNA detection and genotyping, and a fasting blood sample to measure 27 micronutrients. Cohort participants acquired 189 anal HPV infections, 113 of which cleared during the study period. The most frequently acquired HPV genotypes were HPV-52, 53, 84, and 16. Women in the highest quartile of trans-zeaxanthin, trans-anhydro-lutein, trans-, cis-, and total β-carotene had significant 43-50% reduction in the risk of acquisition of any HPV infection compared to women in the lowest quartile. Few associations were observed between micronutrient levels and clearance of transient (≤150 days) anal HPV infections. However, clearance of persistent (>150 days) infections was associated with higher levels of β + γ-tocopherol and lower levels of carotenoids and retinol. Our findings suggest that several carotenoids can reduce the risk and clearance of anal HPV infections that contribute to anal cancer. PMID:20935226
Ebisumoto, Koji; Okami, Kenji; Maki, Daisuke; Saito, Kosuke; Shimizu, Fukuko; Teramura, Takanobu; Kaneda, Shoji; Iida, Masahiro
Several reports have suggested that selected patients with human papillomavirus-related oropharyngeal cancer can be managed with surgery alone. We retrospectively reviewed tonsillar cancer cases to analyze treatment de-intensification after transoral resection. Eighteen patients with tonsillar cancer who had undergone transoral resection were included. The patients' characteristics, p16 status, adverse features, clinical course, overall survival, and relapse-free survival according to p16 status were retrospectively examined. Four lesions showed positive surgical margins and one lesion showed close surgical margin; these patients were treated with postoperative irradiation. Seven p16-positive patients had multiple node metastases and two had extracapsular spread. No p16-positive patients agreed to postoperative irradiation, and recurrence within the surgical field was not observed. The five-year overall and relapse-free survival rates were 89% and 74%, respectively. The five-year relapse-free survival rates of p16-positive and p16-negative patients were 81% and 50%, respectively (p = .075). Postoperative irradiation for cervical lymph node metastases might be avoidable in selected patients with human papillomavirus-related tonsillar cancer. 4.
Ina Marie Angèle Traore
Full Text Available High-risk human papillomavirus (HPV is found in over 99% of cervical cancers. The aim of this study was to determine the prevalence of HPV in a population of women in Bobo-Dioulasso and to identify the high-risk types present in these women. From May to June, 2015, 181 women who came for consultation at the Souro Sanou University Hospital of Bobo-Dioulasso have been included in this study. Uterine endocervical swabs have been taken in these women. DNA obtained by extraction from the samples thus collected was used to determine the prevalence of high-risk human papillomavirus genotypes through real-time PCR. The age of the women ranged from 20 to 56 years with a mean of 35.3±8.1 years. The prevalence of infection by high-risk HPV types was 25.4% (46/181. The most common high-risk HPV genotypes were HPV 39 (18.5%, HPV 52 (16.7%, HPV 18 (14.8%, and HPV 35 (13.0%. HPV 16 which is included in the HPV vaccines was not found in the population studied. This type of study which is the first one in Bobo-Dioulasso has showed a high prevalence of genotypes HPV 39, HPV 52, and HPV 35 which are not yet covered by a vaccine.
Murphy, Jeanne; Mark, Hayley
Cervical cancer screening algorithms have changed with the introduction of testing for human papillomavirus (HPV) and better understanding of the natural history of HPV. This review was undertaken to present recent developments related to cervical cancer screening, with HPV testing as a focus. Specifically, guidelines now recommend initiating cervical cancer screening at age 21, stopping at age 65 to 70 if previous tests are normal, and screening no more than every 2 to 3 years. Human papillomavirus testing is now incorporated into guidelines for cervical cancer screening in the United States, with the major impact being the lengthening of recommended screening intervals. Primary screening with HPV testing, although not yet approved in the United States, may serve to increase access to care for the millions of underserved women worldwide who bear most of the burden of cervical cancer. Despite clear guidelines from authoritative sources, many clinicians (including midwives) overscreen women. In cervical cancer screening, as in many areas of women's health care, performing tests that are unlikely to result in useful information may lead to harm. © 2012 by the American College of Nurse-Midwives.
Arbyn, Marc; Tommasino, Massimo; Depuydt, Christophe; Dillner, Joakim
Abstract: In 2012, the International Agency for Research on Cancer concluded that there was consistent and sufficient epidemiological, experimental and mechanistic evidence of carcinogenicity to humans for 12 HPV types (HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58 and HPV59) for cervical cancer. Therefore, these types were considered as 1A carcinogens. They all belong to the family of the -Papillomaviridae, in particular to the species 5 (HPV51), 6 (HPV56), 7 (H...
Full Text Available Human papillomavirus is known to be the major pathogen of cervical cancer. Here, we report the efficacy of a bivalent human papillomavirus type 16 and 18 DNA vaccine system following repeated dosing in mice and pigs using a recombinant baculovirus bearing human endogenous retrovirus envelope protein (AcHERV as a vector. The intramuscular administration of AcHERV-based HPV16L1 and HPV18L1 DNA vaccines induced antigen-specific serum IgG, vaginal IgA, and neutralizing antibodies to levels comparable to those achieved using the commercially marketed vaccine Cervarix. Similar to Cervarix, AcHERV-based bivalent vaccinations completely blocked subsequent vaginal challenge with HPV type-specific pseudovirions. However, AcHERV-based bivalent vaccinations induced significantly higher cell-mediated immune responses than Cervarix, promoting 4.5- (HPV16L1 and 3.9-(HPV18L1 fold higher interferon-γ production in splenocytes upon stimulation with antigen type-specific pseudovirions. Repeated dosing did not affect the immunogenicity of AcHERV DNA vaccines. Three sequential immunizations with AcHERV-HP18L1 DNA vaccine followed by three repeated dosing with AcHERV-HP16L1 over 11 weeks induced an initial production of anti-HPV18L1 antibody followed by subsequent induction of anti-HPV16L1 antibody. Finally, AcHERV-based bivalent DNA vaccination induced antigen-specific serum IgG immune responses in pigs. These results support the further development of AcHERV as a bivalent human papillomavirus DNA vaccine system for use in preventing the viral infection as well as treating the infected women by inducing both humoral and cell-mediated immune responses. Moreover, the possibility of repeated dosing indicates the utility of AcHERV system for reusable vectors of other viral pathogen vaccines.
Lee, Hee-Jung; Hur, Yoon-Ki; Cho, Youn-Dong; Kim, Mi-Gyeong; Lee, Hoon-Taek; Oh, Yu-Kyoung; Kim, Young Bong
Human papillomavirus is known to be the major pathogen of cervical cancer. Here, we report the efficacy of a bivalent human papillomavirus type 16 and 18 DNA vaccine system following repeated dosing in mice and pigs using a recombinant baculovirus bearing human endogenous retrovirus envelope protein (AcHERV) as a vector. The intramuscular administration of AcHERV-based HPV16L1 and HPV18L1 DNA vaccines induced antigen-specific serum IgG, vaginal IgA, and neutralizing antibodies to levels comparable to those achieved using the commercially marketed vaccine Cervarix. Similar to Cervarix, AcHERV-based bivalent vaccinations completely blocked subsequent vaginal challenge with HPV type-specific pseudovirions. However, AcHERV-based bivalent vaccinations induced significantly higher cell-mediated immune responses than Cervarix, promoting 4.5- (HPV16L1) and 3.9-(HPV18L1) fold higher interferon-γ production in splenocytes upon stimulation with antigen type-specific pseudovirions. Repeated dosing did not affect the immunogenicity of AcHERV DNA vaccines. Three sequential immunizations with AcHERV-HP18L1 DNA vaccine followed by three repeated dosing with AcHERV-HP16L1 over 11 weeks induced an initial production of anti-HPV18L1 antibody followed by subsequent induction of anti-HPV16L1 antibody. Finally, AcHERV-based bivalent DNA vaccination induced antigen-specific serum IgG immune responses in pigs. These results support the further development of AcHERV as a bivalent human papillomavirus DNA vaccine system for use in preventing the viral infection as well as treating the infected women by inducing both humoral and cell-mediated immune responses. Moreover, the possibility of repeated dosing indicates the utility of AcHERV system for reusable vectors of other viral pathogen vaccines.
Grabowski, Mary K; Gravitt, Patti E; Gray, Ronald H; Serwadda, David; Redd, Andrew D; Kigozi, Godfrey; Kong, Xiangrong; Nalugoda, Fred; Wawer, Maria J; Quinn, Thomas C; Tobian, Aaron A R
Limited data are available on human papillomavirus (HPV) infection among human immunodeficiency virus (HIV)-negative or HIV-positive couples followed longitudinally. Genital HPV was assessed in 725 concordant HIV-negative couples and 209 HIV-positive couples enrolled in a male circumcision trial in Rakai, Uganda, using the Roche Linear Array assay, which detects 37 HPV genotypes. Human papillomavirus prevalence and determinants of genotype-specific concordance were assessed at annual visits. Cumulative detection of HPV genotypes over 2 years was also assessed. At enrollment, HPV infection was detected in 54% of HIV-negative women, 56% of HIV-negative men, and 93% of HIV-positive men and women. For HIV-negative couples, genotypic concordance was 30% at baseline (n = 219/725) and declined significantly with age (adjusted prevelance risk ratio [adjPRR] = 0.53; 95% confidence interval [CI] = 0.28-0.93 comparing women aged >40 years to those aged 15-19 years) and male circumcision (adjPRR = 0.60; 95% CI = 0.47-0.77) and increased among couples with recent intercourse (adjPRR = 1.26; 95% CI = 1.04-1.53). These associations were not seen in HIV-positive couples. Among couples with HPV results at all visits, ≥1 of the same genotypes were detected in both partners in 60% of HIV-negative couples and 96% of HIV-positive couples over 2 years. Human papillomavirus genotype-specific concordance is more common in HIV-positive couples, and irrespective of HIV status, the majority of couples exhibit HPV concordance over 2 years.
including human papillomavirus. Cervical cancer, the leading female cancer in Nigeria, arises when there is persistent infection with the high risk human papillomavirus, and this occurs in 5-10% of infected women (Bosch et al., 2002). Despite the fact that cervical cancer remained the only cancer that is vaccine preventable, ...
Bousarghin, Latifa; Touze, Antoine; Gaud, Guillaume; Iochmann, Sophie; Alvarez, Eva; Reverdiau, Pascale; Gaitan, Julien; Jourdan, Marie-Lise; Sizaret, Pierre-Yves; Coursaget, Pierre L
Overexpression of human papillomavirus (HPV E6 and HPV E7) oncogenes in human cervical cells results in the development of cancer, and E6 and E7 proteins are therefore targets for preventing cervical cancer progression. Here, we describe the silencing of E6 and E7 expression in cervical carcinoma cells by RNA interference. In order to increase the efficacy of the RNA interference, HPV pseudovirions coding for a short hairpin RNA (shRNA) sequence were produced. The results indicated the degradation of E6 and E7 mRNAs when shRNA against E6 or E7 were delivered by pseudovirions in HPV-positive cells (CaSki and TC1 cells). E6 silencing resulted in the accumulation of cellular p53 and reduced cell viability. More significant cell death was observed when E7 expression was suppressed. Silencing E6 and E7 and the consequences for cancer cell growth were also investigated in vivo in mice using the capacity of murine TC1 cells expressing HPV-16 E6 and E7 oncogenes to induce fast-growing tumors. Treatment with lentiviruses and HPV virus-like particle vectors coding for an E7 shRNA sequence both resulted in dramatic inhibition of tumor growth. These results show the ability of pseudovirion-delivered shRNA to produce specific gene suppression and provide an effective means of reducing HPV-positive tumor growth.
Full Text Available Difficulties with serology for papillomavirus are associated with the large number of human papillomavirus, cross-reactions between papillomavirus, and to the diversity of lesions and target sites for infection. In addition, the expression of the papillomavirus in the superficial layers of the epithelium gives rise to the weak presentation to immunocompetent cells of viral antigens, which in turn gives rise to a weak serological response. Distinct efforts have been made in previous decades to develop more specific and sensitive serological assays. These former studies use fusion proteins and synthetic peptides, although they remain on the whole uninteresting, due to their lack of sensitivity and specificity. Only in the last few years, and principally due to the advent of various virus-like particles (VLP, have more sensitive and specific assays become available.Las limitaciones para la utilización de la serología para el estudio del virus del papiloma humano con fines clínicos están asociadas con la gran variedad de subtipos humanos, con las reacciones cruzadas que existen entre diversos genotipos, la diversidad de lesiones precursoras de cáncer y con los sitios blancos de infección. Asimismo, la expresión del virus del papiloma humano en las capas superficiales del epitelio dan origen a una débil presentación de células inmunocompetentes de antígenos virales, lo cual origina una elevación de la respuesta serológica. Distintos esfuerzos se han realizado en décadas previas para desarrollar ensayos serológicos más específicos y sensibles. En muchas investigaciones se ha utilizado una fusión de proteínas y péptidos sintéticos que tienen como principal limitación su escasa sensibilidad y especificidad. Sólo en los últimos años, y principalmente debido al arribo de partículas parecidas a este virus, tenemos disponibles ensayos más sensibles y específicos, ampliamente descritos en este artículo.
Wadhera, Priya; Evans, Jennifer L; Stein, Ellen; Gandhi, Monica; Couture, Marie-Claude; Sansothy, Neth; Sichan, Keo; Maher, Lisa; Kaldor, John; Page, Kimberly; Kien
Human papillomavirus is a common sexually transmitted infection and the causative agent for cervical cancer, a frequently occurring malignant disease among women in developing countries. We assessed human papillomavirus awareness prior to the delivery of a brief information and education intervention, and human papillomavirus vaccine provision to female entertainment and sex workers (N = 220). At baseline, only 23.6% of women had heard of human papillomavirus. Following the educational intervention, 90% answered all the human papillomavirus knowledge questions correctly. Of 192 participants attending the first quarterly cohort visit where vaccine was offered, 149 (78%) were eligible for vaccination; HIV-positive (n = 32) and pregnant (n = 11) women were excluded. Acceptance of vaccine among eligible women was universal, and 79.2% completed the three-dose vaccination series. Women who reported use of amphetamine-type stimulants had significantly and independently lower odds of vaccine completion (adjusted odds ratio [AOR] 0.24; 95% confidence interval [CI] 0.08, 0.69). New pregnancies also had an impact on vaccine completion: 5.4% (8/149 5.4%) who started the series had to stop due to new pregnancy. Results demonstrate the effectiveness of a simple education intervention designed to increase human papillomavirus knowledge and the feasibility of successful human papillomavirus vaccine in a population that is often difficult to engage in preventive health care. © The Author(s) 2015.
Badiu, Iuliana; Geuna, Massimo; Heffler, Enrico; Rolla, Giovanni
A 17-year-old girl reported generalised urticaria, eyelid angioedema, rhino-conjunctivitis, dyspnoea and wheezing 1 h after third intramuscular administration of quadrivalent human papilloma virus vaccine (Gardasil). She was treated with antihistamine, and corticosteroids with prompt relief of rhinitis and dyspnoea, while urticaria and angioedema lasted 24 h. Intradermal test with Gardasil, which contains polysorbate 80 (PS80), resulted positive, while skin tests with the bivalent vaccine were negative. Prick test performed with PS80 resulted positive in the patient and negative in ten healthy controls. The CD203 basophil activation test result was negative for PS80 at all the tested dilutions and specific IgE was not found. As flu vaccine was recommended, the authors skin tested two flu vaccine, one containing PS80 (Fluarix, GSK), which resulted positive and another flu vaccine with no adjuvant or preservative (Vaxigrip, Sanofi Pasteur MSD), which gave negative results. The patient then received Vaxigrip without adverse reactions.