Clearance Of Human Papillomavirus Infection Research Articles

The effect of intrauterine devices on acquisition and clearance of human papillomavirus

Previous studies have shown a decrease in cervical cancer associated with intrauterine device use. It has been hypothesized that intrauterine device use may alter the natural history of human papillomavirus infections, preempting development of precancerous lesions of the cervix and cervical cancer, but the effect of intrauterine devices on the natural history of human papillomavirus infection and subsequent development of cervical cancer is poorly understood. The purpose of this study was to evaluate the association between intrauterine device use and cervical high-risk human papillomavirus acquisition and clearance. This is a prospective cohort study conducted from October 2000 through June 2014 among 676 sexually active young women and girls enrolled from family planning clinics in San Francisco, CA. Data were analyzed using a Cox proportional hazards model, including time-varying indicators of intrauterine device use, and adjusting for fixed and time-dependent predictor variables. A total of 85 women used an intrauterine device at some time during follow-up. Among 14,513 study visits, women reported intrauterine device use at 505 visits. After adjusting for potential behavioral confounders, there was no association between intrauterine device use and human papillomavirus acquisition (hazard ratio, 0.50; 95% confidence interval, 0.20-1.23; P= .13) or clearance of human papillomavirus infection (hazard ratio, 1.44; 95% confidence interval, 0.76-2.72; P=.26). Current intrauterine device use is not associated with acquisition or persistence of human papillomavirus infection. Intrauterine device use is safe among women and girls with human papillomavirus infections and at risk for human papillomavirus acquisition. Intrauterine device use may play a role further downstream in the natural history of cervical cancer by inhibiting the development of precancerous lesions of the cervix in human papillomavirus-infectedwomen, or enhancing clearance of established precancerous lesions.

High-risk human papillomavirus infection clearance following conization among patients with cervical intraepithelial neoplasm grade 3 aged at least 45years.

To investigate high-risk human papillomavirus (HPV) infection clearance rates following successful cold knife conization and factors predictive of HPV clearance among patients with cervical intraepithelial neoplasm grade 3. The present retrospective study analyzed clinical data from patients aged at least 45years with cervical intraepithelial neoplasm grade 3 who had undergone successful cold knife conization and attended regular follow-up at Peking Union Medical College Hospital, China, between January 1, 2002 and December 31, 2012. HPV clearance rates and potential indicators for HPV clearance were analyzed. Data from 156 patients were included; persistent high-risk HPV infection was recorded in 78 (50.0%), 45 (28.8%), 35 (22.4%), 24 (15.4%), and 21 (13.5%) patients at 4, 8, 12, 18, and 24months after conization, respectively. Clearance rates were significantly lower among patients aged at least 55years compared with younger patients, with increased odds of persistent HPV infection at 8months (odds ratio [OR] 4.038; 95% confidence interval [CI] 1.766-10.839), 12months (OR 5.923; 95% CI 2.450-16.604), 18months (OR 5.957; 95% CI 2.031-17.469), and 24months (OR 5.327; 95% CI 1.909-17.971) compared with patients aged 45-49years. Age was a prognostic factor for post-operative high-risk HPV infection clearance. Lower clearance rates were observed among patients aged at least 55years.

Relationship between circumcision and human papillomavirus infection: a systematic review and meta-analysis.

Male circumcision (MC) is reported to reduce human papillomavirus (HPV) prevalence in men. However, the efficacy remains imprecise. The aim of this study was to conduct a systematic review and meta-analysis to assess the relationship between MC and genital HPV infection and genital warts. PUBMED, EMBASE, and Web of Science were searched from inception to March 22, 2015. We identified 30 papers, including a total of 12149 circumcised and 12252 uncircumcised men who were evaluated for the association of circumcision with genital HPV or genital warts. Compared with men who were not circumcised, circumcised men may have had significantly reduced odds of genital HPV prevalence (odds ratio [OR]: 0.68; 95% confidence interval [95% CI]: 0.56–0.82). There was no significant association between MC and genital HPV acquisition of new infections (OR: 0.99; 95% CI: 0.62–1.60), genital HPV clearance (OR: 1.38; 95% CI: 0.96–1.97), and prevalence of genital warts (OR: 1.17; 95% CI: 0.63–2.17). This meta-analysis suggests that circumcision reduces the prevalence of genital HPV infections. However, no clear evidence was found that circumcision was associated with decreased HPV acquisition, increased HPV clearance, or decreased the prevalence of genital warts. More studies are required to evaluate adequately the effect of MC on the acquisition and clearance of HPV infections and prevalence of genital warts.

Impact of human papillomavirus (HPV) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment

BACKGROUNDHuman papillomavirus (HPV) vaccines prevent HPV infection and cervical precancers. The impact of vaccinating women with a current infection or after treatment for an HPV-associated lesion is not fully understood.OBJECTIVESTo determine whether HPV-16/18 vaccination influences the outcome of infections present at vaccination and the rate of infection and disease after treatment of lesions.STUDY DESIGNWe included 1711 women (18–25 years) with carcinogenic human papillomavirus infection and 311 women of similar age who underwent treatment for cervical precancer and who participated in a community-based trial of the AS04-adjuvanted HPV-16/18 virus-like particle vaccine. Participants were randomized (human papillomavirus or hepatitis A vaccine) and offered 3 vaccinations over 6 months. Follow-up included annual visits (more frequently if clinically indicated), referral to colposcopy of high-grade and persistent low-grade lesions, treatment by loop electrosurgical excisional procedure when clinically indicated, and cytologic and virologic follow-up after treatment. Among women with human papillomavirus infection at the time of vaccination, we considered type-specific viral clearance, and development of cytologic (squamous intraepithelial lesions) and histologic (cervical intraepithelial neoplasia) lesions. Among treated women, we considered single-time and persistent human papillomavirus infection, squamous intraepithelial lesions, and cervical intraepithelial neoplasia 2+. Outcomes associated with infections absent before treatment also were evaluated. Infection-level analyses were performed and vaccine efficacy estimated.RESULTSMedian follow-up was 56.7 months (women with human papillomavirus infection) and 27.3 months (treated women). There was no evidence of vaccine efficacy to increase clearance of human papillomavirus infections or decrease incidence of cytologic/histologic abnormalities associated with human papillomavirus types present at enrollment. Vaccine efficacy for human papillomavirus 16/18 clearance and against human papillomavirus 16/18 progression from infection to cervical intraepithelial neoplasia 2+ were −5.4% (95% confidence interval −19,10) and 0.3% (95% confidence interval −69,41), respectively. Among treated women, 34.1% had oncogenic infection and 1.6% had cervical intraepithelial neoplasia 2+ detected after treatment, respectively, and of these 69.8% and 20.0% were the result of new infections. We observed no significant effect of vaccination on rates of infection/lesions after treatment. Vaccine efficacy estimates for human papillomavirus 16/18 associated persistent infection and cervical intraepithelial neoplasia 2+ after treatment were 34.7% (95% confidence interval −131, 82) and −211% (95% confidence interval −2901, 68), respectively. We observed evidence for a partial and nonsignificant protective effect of vaccination against new infections absent before treatment. For incident human papillomavirus 16/18, human papillomavirus 31/33/45, and oncogenic human papillomavirus infections post-treatment, vaccine efficacy estimates were 57.9% (95% confidence interval −44, 88), 72.9% (95% confidence interval 29, 90), and 36.7% (95% confidence interval 1.5, 59), respectively.CONCLUSIONWe find no evidence for a vaccine effect on the fate of detectable human papillomavirus infections. We show that vaccination does not protect against infections/lesions after treatment. Evaluation of vaccine protection against new infections and resultant lesions warrants further consideration in future studies.

Human papillomavirus infection and lymphoma incidence using cervical conization as a surrogate marker: a Danish nationwide cohort study.

Persistent human papillomavirus (HPV) infection may promote carcinogenesis by hyperactivation of the immune system. We, therefore, explored the associations between HPV infection and risk of Hodgkin and non-Hodgkin lymphoma in a nationwide cohort study using conization as a surrogate marker. We identified all Danish women who underwent conization between 1978 and 2011. We computed standardized incidence ratios and 95% confidence intervals for Hodgkin and non-Hodgkin lymphoma based on national cancer incidence rates. Among 87 435 women who underwent conization, we noted an increased incidence of Hodgkin (standardized incidence ratio 1.48, 95% confidence interval 1.05-2.02) but only a slight increase for non-Hodgkin lymphoma (standardized incidence ratio 1.10, 95% confidence interval 0.97-1.25). As measured by conization, HPV infection is associated with an increased risk of lymphoma. This association may be attributable to a chronic immune activation induced by persistent HPV infection and/or failure of the immune system both to clear HPV infection and to control lymphoma development. Copyright © 2015 John Wiley & Sons, Ltd.

Human Papillomavirus (HPV) Infections and the Importance of HPV Vaccination.

HPV persistence is necessary for the development of anogenital cancer. Studies show that cervical and anal HPV infections in women and in men who have sex with men are common. Clearance of HPV infection is similarly common; few individuals show persistence unless they are HIV-infected. HIV strongly influences the development of cervical and anal cancer, as well as their pre-malignant counterparts. Women with cervical and vulvar HPV-associated lesions have higher rates of anal cancer than the general population. HPV also plays an important role in pathogenesis of head and neck cancers, particularly oropharyngeal cancer. Two commercially available HPV vaccines have been proven to be safe and efficacious against cervical HPV16/18 infections and associated precancerous lesions; one of these has also been shown to prevent HPV16/18-associated anal lesions. The FDA has also just approved a new nonavalent HPV vaccine. HPV vaccines will play an important role in prevention of HPV-associated cancers.

Impact of the quadrivalent HPV vaccine on disease recurrence in men exposed to HPV Infection: a randomized study.

Human papillomavirus (HPV) is one of the most common sexually transmitted infections and is the cause of several different diseases in men and women. Although little is known about HPV infection in men, they are also in the risk group of HPV infection and play an important role in transmitting the virus to women. To define the efficacy of the HPV vaccine through cross-immunization and its role in clearance of HPV infection, and to assess infection-associated factors in men. This prospective randomized clinical study enrolled 171 evaluable men with genital warts between June 2009 and October 2013. After the initial treatment intervention, 91 patients were randomly assigned to receive HPV vaccine in three doses. Eighty patients were in the control (unvaccinated) group. One hundred-eleven men were single and 60 men were married. Patients who had previous treatment for pre-existing warts and medical disorders that needed chronic treatment or immunosuppression were not included in the randomization. Also 29 men with follow-up less than 12 months and incomplete vaccination were not included. The patients were assessed regarding age, condom use, marital status, number of visible genital warts, and smoking status. Post-treatment follow-up was monthly up to 12th month. Mean age was 34 ± 7.6. One hundred fifteen patients were smokers. For the recurrence of warts, age, smoking, vaccination status were insignificant and marital status was significant in the univariable analysis; only marital status preserved significance (HR: 2.0 CI:1.29-3.12 P = 0.002) in the multivariable analysis including vaccination status, marital status, and smoking. Among the investigated factors vaccination status was not but marital status significantly influenced wart recurrence. Married men had more recurrences in our population. Larger multicenter randomized clinical trials are lacking and seriously required to investigate the therapeutic effect of current quadrivalent HPV vaccine in genital warts.

Oral squamous cell carcinoma positive for p16/human papilloma virus in post allogeneic stem cell transplantation: 2 cases and review of the literature

Complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT) includes the risk of secondary malignancies. This may be related to mechanisms including radiation and chemotherapy regimens, chronic graft-versus-host disease, inflammation, and prolonged imunosuppression. Oral squamous cell carcinoma (OSCC) is a complication associated with chronic graft-versus-host disease after allo-HSCT. Although human papillomavirus (HPV) is known to be associated with OSCC, the role of HPV in development of OSCC in post-HSCT patients has not been studied. We identified 2 cases of OSCC in allo-HSCT recipients. Both biopsy specimens tested positive for p16(INK4A), a surrogate marker for HPV. We propose that the association of OSCC and HPV in patients after allo-HSCT may not be incidental. Clinical implications of these cases may imply the need for a HPV screening, early intervention, and consideration of anti-HPV vaccination in this population. The effectiveness of such interventions could be validated in a prospective clinical study.

MP16-19 IMPACT OF THE QUADRIVALENT HPV VACCINE FOR MEN WHO EXPOSED TO HPV INFECTION

You have accessJournal of UrologyInfections/Inflammation of the Genitourinary Tract: Prostate & Genitalia1 Apr 2014MP16-19 IMPACT OF THE QUADRIVALENT HPV VACCINE FOR MEN WHO EXPOSED TO HPV INFECTION Tayyar Alp Ozkan, Enis Coskuner, Ayhan Karakose, Ozdal Dillioglugil, and Ibrahim Cevik Tayyar Alp OzkanTayyar Alp Ozkan More articles by this author , Enis CoskunerEnis Coskuner More articles by this author , Ayhan KarakoseAyhan Karakose More articles by this author , Ozdal DillioglugilOzdal Dillioglugil More articles by this author , and Ibrahim CevikIbrahim Cevik More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.592AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Human papillomavirus (HPV) is one of the most common sexually transmitted infections. In 2009, FDA recommended HPV vaccine for the prevention of external genital lesions caused by HPV 6, 11, 16, or 18. There are conflicting results regarding cross protection from naturally occurring HPV infection. According to recent studies HPV vaccination can induce neutralizing antibodies across HPV species. Our purpose was to define the importance of immunization and its role in clearance of HPV infection and to assess infection-associated factors in men. METHODS This prospective randomized trial enrolled 200 men with genital warts (GW), between June, 2009 and October, 2013. GW were diagnosed solely with their clinical features and their reaction to the aceto-white. Pathologic examination was performed in suspicious cases. Initial treatment was local excision with electrocautery or electrocautery alone in all patients. After the initial intervention, 200 patients were randomly assigned to receive a HPV vaccine in three doses (0, 2, 6 mos). Hundred patients were in the control (unvaccinated) group. All men were circumcised and reported only female sexual partners. Thirty-nine men were excluded due to pre-existing medical disorders that needed chronic treatment or caused immunosuppression, follow-up (F/U) less than 12 months and incomplete vaccination. Finally, 171 consecutive patients were included in study. There were 91 men in the vaccinated group and 80 men in the control group. One hundred-eleven were single and 60 men were married. The patients were assessed regarding age, marital status (MS), number of GW, physical examination and smoking status. Post-treatment F/U was monthly up to 6 months and one more at the 12th mo. GW recurrences were analyzed with Cox proportional hazards model. RESULTS Mean age was 34±7.6. One hundred-fifteen (67.25%) patients were smokers. For the recurrence of GW, age, smoking, vaccination status (VS) were insignificant and MS was significant (p<.001) in the univariable analysis; MS (Figure) preserved significance (HR:2.0 CI:1.29-3.12 p=.002) in the multivariable analysis (with VS, MS). CONCLUSIONS Among the investigated factors not VS but MS significantly influenced wart recurrence. Interestingly, married men had more recurences in our population. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e161 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Tayyar Alp Ozkan More articles by this author Enis Coskuner More articles by this author Ayhan Karakose More articles by this author Ozdal Dillioglugil More articles by this author Ibrahim Cevik More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Male circumcision and the incidence and clearance of genital human papillomavirus (HPV) infection in men: the HPV Infection in men (HIM) cohort study

BackgroundReported associations of male circumcision (MC) with human papillomavirus (HPV) infection in men have been inconsistent.Methods4,033 healthy men were examined every six months for a median of 17.5 months. In each study visit, exfoliated cell specimens from the coronal sulcus/glans penis, penile shaft, and scrotum were collected and combined into one sample per person for HPV DNA detection. Samples were tested for 37 HPV types. Cox proportional hazards models were used to evaluate the association between MC and the incidence and clearance of HPV infections and specific genotypes.ResultsThe overall incidence of new HPV infections did not differ by MC status (for any HPV, adjusted hazard ratio (aHR) 1.08, 95% confidence interval (CI) 0.91-1.27). However, incidence was significantly lower among circumcised versus uncircumcised men for HPV types 58 (p = 0.01), 68 (p < 0.001), 42 (p = 0.01), 61 (p < 0.001), 71 (p < 0.001), 81 (p = 0.04), and IS39 (p = 0.01), and higher for HPV types 39 (p = 0.01) and 51 (p = 0.02). Despite the lack of an overall association in the risk of HPV clearance by MC (for any HPV, aHR 0.95, 95% CI 0.88-1.02), median times to clearance were significantly shorter among circumcised than uncircumcised men for HPV types 33 (p = 0.02) and 64 (p = 0.04), and longer for HPV types 6 (p < 0.001), 16 (p < 0.001), and 51 (p = 0.02).ConclusionsMC is not associated with the incidence and clearance of genital HPV detection, except for certain HPV types. The use of a single combined sample from the penis and scrotum for HPV DNA detection likely limited our ability to identify a true effect of MC at the distal penis.

Role of Innate Immunity against Human Papillomavirus (HPV) Infections and Effect of Adjuvants in Promoting Specific Immune Response

During the early stages of human papillomavirus (HPV) infections, the innate immune system creates a pro-inflammatory microenvironment by recruiting innate immune cells to eliminate the infected cells, initiating an effective acquired immune response. However, HPV exhibits a wide range of strategies for evading immune-surveillance, generating an anti-inflammatory microenvironment. The administration of new adjuvants, such as TLR (Toll-like receptors) agonists and alpha-galactosylceramide, has been demonstrated to reverse the anti-inflammatory microenvironment by down-regulating a number of adhesion molecules and chemo-attractants and activating keratinocytes, dendritic (DC), Langerhans (LC), natural killer (NK) or natural killer T (NKT) cells; thus, promoting a strong specific cytotoxic T cell response. Therefore, these adjuvants show promise for the treatment of HPV generated lesions and may be useful to elucidate the unknown roles of immune cells in the natural history of HPV infection. This review focuses on HPV immune evasion mechanisms and on the proposed response of the innate immune system, suggesting a role for the surrounding pro-inflammatory microenvironment and the NK and NKT cells in the clearance of HPV infections.

Incidence and clearance of oral human papillomavirus infection in men: the HIM cohort study

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 needed to inform development of infection-related prevention efforts. US National Cancer Institute, Merck Sharp & Dohme.

Single CpG Site hypomethylation of MAL gene might be associated with human papillomavirus persistent infection

Objective: It has been well known that cervical intraepithelial neoplasia is preceded by persistent infections with human papillomavirus (HPV) types that carry a high oncogenic risk. About 80% of young women who become infected with HPV have transient infections that clear within 12-18 months. Only a small fraction of women with HPV infection eventually develop persistent infections. No definitive molecular evidence is associated with persistent infection. In this study, we aimed to determine the difference of promotor methylation level in cervical cell genes (ADCYAP1, PAX1, CAMD1, and MAL) between persistence and clearance of HPV infection.

Associations between human herpesvirus-6, human papillomavirus and cervical cancer

Cervical cancer (CxCa) is the second most common cancer among women globally. Human papillomavirus (HPV) infection is thought to be a necessary, but not sufficient, causal factor in CxCa development. Why some women are able to clear HPV infection with no adverse effects, whereas others develop cancer, remains unclear. HHV-6 has demonstrated transformative abilities and has been shown to be present in the genital tract. However, based on the current evidence, we cannot conclude that HHV-6 is a co-factor in HPV-associated carcinogenesis. Nonetheless, future research is warranted because of several crucial gaps in the literature.

Establishment of a Korea HPV cohort study

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

Persistence or Clearance of Human Papillomavirus Infections in Women in Ouro Preto, Brazil

Persistent high-risk (HR) human papillomavirus (HPV) infection is necessary for development of precursor lesions and cervical cancer. We investigate persistence and clearance of HPV infections and cofactors in unvaccinated women. Cervical samples of 569 women (18–75 years), received for routine evaluation in the Health Department of Ouro Preto, Brazil, were collected and subjected to PCR (MY09/11 or GP5+/6+ primers), followed by RFLP or sequencing. All women were interviewed to collect sociodemographic and behavioral information. Viral infection persistence or clearance was reevaluated after 24 months and was observed in 59.6% and 40.4% of women, respectively. HPVs 16, 33, 59, 66, 69, and 83 (HR) were the most persistent types whereas HPVs 31, 45, and 58 were less persistent. Clearance or persistence did not differ between groups infected by HPVs 18, 53, and 67. In low-risk (LR) types, HPV 6 infected samples were associated with clearance, while HPV 11, 61, 72, or 81 infected samples were persistent in the follow-up. No statistically significant association was detected between persistent HPV infections and sociodemographic and behavioral characteristics analyzed. To study persistence or clearance in HPV infection allows the identification of risk groups, cofactors, and strategies for prevention of cervical cancer.

Risk of high-grade cervical intraepithelial neoplasia during follow-up in HPV-positive women according to baseline p16-INK4A results: a prospective analysis of a nested substudy of the NTCC randomised controlled trial

Immunostaining for p16-INK4A (henceforth p16) is a sensitive and specific method for detection of high-grade cervical intraepithelial neoplasia (CIN) in women infected with human papillomavirus (HPV), but longitudinal data have not been obtained. We investigated the relation between p16 status and risk of CIN during 3 years of follow-up. Women aged 25-60 years were enrolled between June 10, 2003, and Dec 31, 2004, in a multicentre randomised trial comparing HPV testing with cytology. HPV-positive women were referred for colposcopy and, in seven of nine centres, were tested for p16 overexpression by immunostaining. If no CIN was detected, these women were followed up at yearly intervals until clearance of HPV infection. The primary endpoint was histologically confirmed CIN of grade 2 or worse (CIN of grade 2 [CIN2], CIN of grade 3 [CIN3], or invasive cervical cancer) at recruitment or during follow-up. We calculated the absolute and relative risks by p16 status at recruitment. We also calculated the longitudinal sensitivity of p16 testing. Additionally, we assessed the relative sensitivity of an alternative strategy (referral to colposcopy and follow-up of only HPV-positive, p16-positive women) versus conventional cytology in two age groups. Percentages were weighted by the inverse of the tested fraction. The trial in which this study is nested is registered, number ISRCTN81678807. Of 1042 HPV-positive women who were tested for p16 with no CIN detected during the first round of screening, 944 (91%) had further HPV tests. 793 (84%) of these 944 were followed up until detection of CIN2 or worse, HPV infection clearance, or for at least 3 years. CIN2 or worse was detected during follow-up in more p16-positive women (31 of 365, 8·8% [95% CI 5·8-11·8]) than in p16-negative women (17 of 579, 3·7% [1·9-5·4]; relative risk [RR] 2·61 [95% CI 1·49-4·59]). RR was higher in women aged 35-60 years at recruitment (3·37 [1·39-8·15]) than in those aged 25-34 years (2·15 [1·00-4·61]), but age was not a significant modifier. CIN3 or worse was detected during follow-up in more p16-positive women (16 of 365, 4·4% [2·3-6·6]) than in p16-negative women (six of 579, 1·3% [0·2-2·3]; RR 3·90 [95% CI 1·57-9·68]). Longitudinal sensitivity of p16 testing for detection of CIN3 or worse during follow-up at all ages was 77·8% (95% CI 63·9-91·6). The relative sensitivity of the alternative strategy compared with conventional cytology was 2·08 (1·13-3·56) in women aged 35-60 years and 2·86 (1·28-5·36) in those aged 25-34 years. HPV-positive, p16-negative women aged 35-60 years had a higher cumulative risk of CIN3 or worse during recruitment or follow-up (2·0%, 95% CI 0·3-3·7) than did HPV-negative women (0·01%, 0-0·04) or those who were cytologically normal (0·04%, 0·02-0·09) at recruitment. p16 overexpression is a marker for CIN2 or worse or for development of CIN2 or worse within 3 years in HPV-positive women, especially those aged 35-60 years. HPV-positive, p16-positive women need immediate colposcopy and, if the assessment is negative, annual follow-up. Immediate colposcopy can be avoided in HPV-positive, p16-negative women, who can be safely managed with repeat screening after 2-3 year intervals. European Union; Italian Ministry of Health; Regional Health Administrations of Piemonte, Tuscany, Veneto and Emilia Romagna; and Public Health Agency of Lazio Region.

HPV in Female Partners Increases Risk of Incident HPV Infection Acquisition in Heterosexual Men in Rural Central Mexico

Knowledge about the incidence, clearance, and factors associated with human papilloma virus (HPV) infection in men is lacking, and much of what is available focuses on high-risk groups. A prospective cohort study was carried out with 504 heterosexual males from Mexico State, Mexico. Participants were monitored for 4 years at intervals of approximately 4 months, with a median total duration of follow-up of 19.8 months. The presence of cervical HPV in female sexual partners was evaluated as a risk factor. HPV DNA testing was conducted using the polymerase chain reaction technique. Risk factors associated with the incidence and clearance of HPV infection were evaluated through survival analysis. The cumulative incidence of infection with any HPV type at 12 months was 15% [95% confidence interval (CI), 0.12-0.20]. About 72% of men with incident HPV cleared the infection by 12 months. The presence of cervical HPV in a man's female sex partner was the main determinant for males acquiring HPV infection of any type [adjusted HR (AHR), 2.1; 95% CI, 1.1-3.8] and oncogenic HPV infection (AHR, 4.1; 95% CI, 2.1-8.0), while having a history of anal sexual relations with women was statistically associated with acquiring nononcogenic HPV (AHR, 1.8; 95% CI, 1.1-2.9). The incidence of genital HPV infection in this population is relatively low, with relatively quick acquisition and clearance rates. Cervical HPV infection in men's female sexual partners was the main risk factor for genital HPV infection in men.

Male Circumcision and Genital Human Papillomavirus

Human papillomavirus (HPV) infection is the principal cause of invasive cervical cancer. There is some evidence that male circumcision (MC) may protect against HPV infection and related disease in both men and women. The purpose of this study was to conduct a systematic review of the literature to assess the association between MC and genital HPV infection indicators including genital warts. A systematic search of Medline was conducted to identify all relevant studies from February 1971 to August 2010. Effect estimates were included in random effects models. A total of 21 studies with 8046 circumcised and 6336 uncircumcised men were included in the meta-analysis. MC was associated with a statistically significant reduced odds of genital HPV prevalence (odds ratio = 0.57, 95% confidence interval: 0.42-0.77). This association was also observed for genital high-risk HPV prevalence in 2 randomized controlled trials (odds ratio = 0.67, 95% confidence interval: 0.54-0.82). No associations were found between MC and genital HPV acquisition of new infections, genital HPV clearance, or genital warts. This meta-analysis shows a robust inverse association between MC and genital HPV prevalence in men. However, more studies are needed to adequately assess the effect of MC on the acquisition and clearance of HPV infections. MC could be considered as an additional one-time preventative intervention likely to reduce the burden of HPV-related diseases both in men and women, particularly among those countries in which HPV vaccination programs and cervical screening are not available.

Transitional Probability-Based Model for HPV Clearance in HIV-1-Positive Adolescent Females

BackgroundHIV-1-positive patients clear the human papillomavirus (HPV) infection less frequently than HIV-1-negative. Datasets for estimating HPV clearance probability often have irregular measurements of HPV status and risk factors. A new transitional probability-based model for estimation of probability of HPV clearance was developed to fully incorporate information on HIV-1-related clinical data, such as CD4 counts, HIV-1 viral load (VL), highly active antiretroviral therapy (HAART), and risk factors (measured quarterly), and HPV infection status (measured at 6-month intervals).Methodology and FindingsData from 266 HIV-1-positive and 134 at-risk HIV-1-negative adolescent females from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort were used in this study. First, the associations were evaluated using the Cox proportional hazard model, and the variables that demonstrated significant effects on HPV clearance were included in transitional probability models. The new model established the efficacy of CD4 cell counts as a main clearance predictor for all type-specific HPV phylogenetic groups. The 3-month probability of HPV clearance in HIV-1-infected patients significantly increased with increasing CD4 counts for HPV16/16-like (p<0.001), HPV18/18-like (p<0.001), HPV56/56-like (p = 0.05), and low-risk HPV (p<0.001) phylogenetic groups, with the lowest probability found for HPV16/16-like infections (21.60±1.81% at CD4 level 200 cells/mm3, p<0.05; and 28.03±1.47% at CD4 level 500 cells/mm3). HIV-1 VL was a significant predictor for clearance of low-risk HPV infections (p<0.05). HAART (with protease inhibitor) was significant predictor of probability of HPV16 clearance (p<0.05). HPV16/16-like and HPV18/18-like groups showed heterogeneity (p<0.05) in terms of how CD4 counts, HIV VL, and HAART affected probability of clearance of each HPV infection.ConclusionsThis new model predicts the 3-month probability of HPV infection clearance based on CD4 cell counts and other HIV-1-related clinical measurements.