Jeanne M. Pimenta

Human Papillomavirus Genotype Distribution in Low-Grade Cervical Lesions: Comparison by Geographic Region and with Cervical Cancer

Low-grade squamous intraepithelial lesions (LSIL) associated with certain human papillomavirus (HPV) genotypes may preferentially progress to cervical cancer. HPV genotyping may thus have the potential to improve the effectiveness of screening programs and to reduce overtreatment. LSIL cases (n = 8,308) from 55 published studies were included in a meta-analysis. HPV genotype distribution was assessed by geographic region and in comparison with published data on cervical squamous cell carcinoma (SCC). HPV detection in LSIL was 80% in North America but less than 70% in other regions, most likely reflecting regional differences in LSIL diagnosis. Among 5,910 HPV-positive LSILs, HPV16 was the most common genotype (26.3%) followed by HPV31 (11.5%), HPV51 (10.6%), and HPV53 (10.2%). HPV-positive LSILs from Africa were 2-fold less likely to be infected with HPV16 than those in Europe, and HPV-positive LSILs from North America were more likely to be infected with HPV18 than those from Europe or South/Central America. Interpretation for rarer genotypes was hampered by variation in HPV testing methodology. SCC/LSIL prevalence ratios indicated that HPV16 was 2-fold and HPV18 was 1.5-fold more common in SCC than in HPV-positive LSIL, thus appearing more likely to progress than other high-risk genotypes (SCC/LSIL prevalence ratios between 0.05 and 0.85). HPV53 and HPV66 showed SCC/LSIL ratios of 0.02 and 0.01, respectively. HPV genotype distribution in LSIL differs from that in cervical cancer, highlighting the importance of HPV genotype in the risk of progression from LSIL to malignancy. Some regional differences in the relative importance of HPV genotypes in LSIL were noted.

Human papillomavirus type distribution in anal cancer and anal intraepithelial lesions.

A systematic review was conducted of HPV type distribution in anal cancer and anal high‐grade and low‐grade squamous intraepithelial lesions (HSIL and LSIL). A Medline search of studies using PCR or hybrid capture for HPV DNA detection was completed. A total of 1,824 cases were included: 992 invasive anal cancers, 472 HSIL cases and 360 LSIL cases. Crude HPV prevalence in anal cancer, HSIL, and LSIL was 71, 91 and 88%, respectively. HPV16/18 prevalence was 72% in invasive anal cancer, 69% in HSIL and 27% in LSIL. The HPV 16 and/or 18 prevalence in invasive anal cancer cases was similar to that reported in invasive cervical cancer. If ongoing clinical trials show efficacy in preventing anal HPV infection and associated anal lesions, prophylactic HPV vaccines may play an important role for the primary prevention of these cancers in both genders.

Systematic review of human papillomavirus prevalence in invasive penile cancer

ObjectiveType-specific prevalence data of human papillomavirus (HPV) DNA in penile carcinoma are needed to determine the potential impact of HPV prophylactic vaccines, assuming demonstrated efficacy in men.MethodsA review was conducted using search terms including HPV and penile cancer. Studies using polymerase chain reaction (PCR) assays for HPV DNA detection in invasive penile carcinoma were included.ResultsA total of 1,266 squamous cell carcinoma (SCC) cases contributed data from 30 studies. The number of SCC was similar in Europe (28.2%), North America (27.6%), South America (23.9%) and Asia (20.4%). All SCC were histologically confirmed with biopsies for DNA detection. Most commonly used PCR primers were type-specific (35.2%), and combination PCR (18.2%). HPV prevalence was 47.9%, ranging from 22.4% in verrucous SCC to 66.3% for the basaloid/warty subtypes. HPV16 (30.8%), HPV6 (6.7%) and HPV18 (6.6%) were the most prevalent types. HPV16 and/or HPV 18 prevalence was 36.7%.ConclusionsHPV DNA was detected in half of SCC, with HPV16 being the most common type. If proven efficacious in men, prophylactic vaccines targeting carcinogenic types HPV16 and 18 could potentially reduce approximately one-third of incident SCC.

Age-Specific Prevalence of Infection with Human Papillomavirus in Females : A Global Review

PURPOSE Global data on age-specific prevalence of human papillomavirus (HPV) infection overall, and for high-risk HPV types 16 and 18, are essential for the future implementation of HPV prophylactic vaccines for cervical cancer prevention. METHODS A systematic review of peer-reviewed publications was conducted to summarize worldwide data on genital HPV-DNA prevalence in women. Studies with clear descriptions of polymerase chain reaction or hybrid capture detection assays were included. RESULTS A total of 346,160 women were included in 375 studies. Of 134 studies with age-stratified HPV prevalence data (116 low sexual risk populations, 18 high sexual risk populations), over 50% were from Europe and the Middle East (38%) and North America (19%), with smaller proportions from Asia and Australia (21%), Central and South America (11%), and Africa (10%). Across all geographical regions, data on HPV prevalence were generally limited to women over 18 years of age. Consistently across studies, HPV infection prevalence decreased with increasing age from a peak prevalence in younger women (< or =25 years of age). In middle-aged women (35-50 years), maximum HPV prevalence differed across geographical regions: Africa (approximately 20%), Asia/Australia (approximately 15%), Central and South America (approximately 20%), North America (approximately 20%), Southern Europe/Middle East (approximately 15%), and Northern Europe (approximately 15%). Inconsistent trends in HPV prevalence by age were noted in older women, with a decrease or plateau of HPV prevalence in older ages in most studies, whereas others showed an increase of HPV prevalence in older ages. Similar trends of HPV 16 and/or 18 prevalence by age were noted among 12 populations with available data. DISCUSSION Genital HPV infection in women is predominantly acquired in adolescence, and peak prevalence in middle-aged women appears to differ across geographical regions. Worldwide variations in HPV prevalence across age appear to largely reflect differences in sexual behavior across geographical regions. Further studies of HPV prevalence in adolescents are needed for all geographic regions.

Human Papillomavirus Type-Distribution in Vulvar and Vaginal Cancers and Their Associated Precursors

OBJECTIVE: Data on human papillomavirus (HPV) prevalence in vulvar and vaginal cancers are limited. These data are important to predict the potential future effect of prophylactic HPV vaccines. Our aim was to conduct a systematic review of HPV type distribution in vulvar and vaginal invasive carcinomas, vulvar intraepithelial neoplasia (VIN), and vaginal intraepithelial neoplasia. DATA SOURCES: A MEDLINE search was conducted using the terms vulvar/vaginal cancer, intraepithelial neoplasia, and HPV/human papillomavirus through September 2007 with no specified start date or language restrictions. METHODS OF STUDY SELECTION: A total of 725 abstracts (564 vulvar, 161 vaginal) were reviewed, of which 67 studies (56 vulvar, 11 vaginal) met the inclusion criteria of using polymerase chain reaction (PCR) or hybrid capture assays for HPV DNA detection and having more than one case with HPV data available. TABULATION, INTEGRATION AND RESULTS: This review identified 2,790 vulvar (1,379 invasive, 1,340 VIN2/3, 71 VIN1) and 315 vaginal cases (83 invasive, 166 vaginal intraepithelial neoplasia 2/3, 66 vaginal intraepithelial neoplasia 1). Most cases were from North America and Europe (87.2%), with few from Asia (5.5%) and South America (7.3%). Human papillomavirus prevalence in vulvar cancer, VIN2/3, and VIN1 was 40.1%, 80.4%, and 77.5%, respectively. HPV prevalence in vaginal cancer, vaginal intraepithelial neoplasia (VAIN)2/3, and VAIN1 was relatively higher at 65.5%, 92.6%, and 98.5%, respectively. HPV16 was the most common type in vulvar (29.3%) and vaginal (55.4%) cancers, VIN2/3 (71.2%) and VAIN2/3 (65.8%). CONCLUSION: Human papillomavirus prevalence was higher among vaginal than vulvar cases, and HPV16 accounted for most HPV-positive cases for both cancers. Although the potential effect of HPV vaccines on these gynecologic cancers may not be as high as for cervical cancer due to their more diverse causes, vaccinating young women against HPV16/18 may help to reduce the incidence of HPV-related cases.

Age-Specific Prevalence of Human Papillomavirus Infection in Males: A Global Review

PURPOSE Global data on age-specific prevalence of human papillomavirus (HPV) infection in males, especially for oncogenic HPV types 16 and 18, are essential for future efforts to prevent HPV-related diseases, including expanded access to HPV prophylactic vaccines for boys and young men. METHODS A systematic review of peer-reviewed publications was conducted to summarize worldwide data on genital HPV-DNA prevalence in men. Studies using polymerase chain reaction or hybrid capture detection assays were included. RESULTS Approximately 6,600 abstracts were identified. Of them, 64 reported age-specific HPV prevalence and were included in the review. Of these, 38 were from populations at high risk of HPV infections, such as sexually transmitted infection clinic attendees, human immunodeficiency virus-positive males, and male partners of women with HPV infection or abnormal cytology. The largest proportions of studies were from Europe (38%) and North America (25%), with smaller proportions from Central and South America (19%), Asia (11%), and Africa (5%). Across all regions, data on HPV prevalence were generally limited to men >18 years of age. HPV prevalence was high among sexually active men in all regions but with considerable variation, from 1% to 84% among low-risk men and from 2% to 93% among high-risk men. Peak HPV prevalence spanned a wide range of ages and was generally not concentrated in the younger age groups. Age-specific prevalence curves were relatively flat or declined only slightly following peak prevalence. CONCLUSIONS Genital HPV infection in men varies widely, both between and within high- and low-risk groups and by geographic region. Compared with that in women, HPV prevalence in men seems to peak at slightly older ages and remains constant or decreases slightly with increasing age, suggesting persistent HPV infection or a higher rate of reinfection.

Opportunistic screening for genital chlamydial infection. I: Acceptability of urine testing in primary and secondary healthcare settings

Objectives: To determine the acceptability of opportunistic screening for Chlamydia trachomatis in young people in a range of healthcare settings. Design: An opportunistic screening programme (1 September 1999 to 31 August 2000) using urine samples tested by ligase chain reaction (LCR). Data on uptake and testing were collected and in-depth interviews were used for programme evaluation. Setting: General practice, family planning, genitourinary medicine clinics, adolescent sexual health clinics, termination of pregnancy clinics, and women’s services in hospitals (antenatal, colposcopy, gynaecology and infertility clinics) in two health authorities (Wirral and Portsmouth and South East Hampshire). Main participants: Sexually active women aged between 16 and 24 years attending healthcare settings for any reason. Main outcome measures: Uptake data: proportion of women accepting a test by area, healthcare setting, and age; overall population coverage achieved in 1 year. Evaluation data: participants’ attitudes and views towards opportunistic screening and urine testing. Results: Acceptance of testing by women (16–24 years) was 76% in Portsmouth and 84% in Wirral. Acceptance was lower in younger women (Portsmouth only) and varied by healthcare setting within each site. 50% of the target female population were screened in Portsmouth and 39% in Wirral. Both the opportunistic offer of screening and the method of screening were universally acceptable. Major factors influencing a decision to accept screening were the non-invasive nature of testing and treatment, desire to protect future fertility, and the experimental nature of the screening programme. Conclusions: An opportunistic model of urine screening for chlamydial infection is a practical, universally acceptable method of screening.

Opportunistic screening for genital chlamydial infection. II: prevalence among healthcare attenders, outcome, and evaluation of positive cases.

Objectives: To determine the prevalence and treatment outcomes among young women screened opportunistically for genital Chlamydia trachomatis and to evaluate the impact of screening in those participating. Design: An opportunistic screening programme (1 September 1999 to 31 August 2000) using urine samples, tested by ligase chain reaction (LCR). In-depth interviews were used for programme evaluation. Setting: Screening was offered in two health authorities at general practice, family planning, genitourinary medicine (GUM), adolescent sexual health, termination of pregnancy clinics and women’s services in hospitals (antenatal, colposcopy, gynaecology and infertility clinics). Main participants: Sexually active women (16–24 years) attending for any reason. Main outcome measures: Screening data: prevalence of infection by age and healthcare setting; proportion of positive patients attending for treatment. Evaluation data: participants’ attitudes and views towards screening and follow up. Results: In total, 16 930 women (16–24 years) were screened. Prevalence was higher in younger women (16–20) than those aged 21–24 years and was highly variable at different healthcare settings (range 3.4%–17.6%). Prevalence was approximately 9% in general practice. The role of the project health advisers in managing results and coordinating treatment of positive individuals was essential; the vast majority of all positives were known to be treated. Women felt that screening was beneficial. Improving awareness and education about sexually transmitted infections is required to alleviate negative reactions associated with testing positive for infection. Conclusions: Prevalence of infection outside GUM clinics is substantial and opportunistic screening using urine samples is an acceptable method of reaching individuals with infection who do not normally present at specialist clinics.

Patterns of persistent genital human papillomavirus infection among women worldwide: A literature review and meta‐analysis

Persistent high‐risk human papillomavirus (HR‐HPV) infection is the strongest risk factor for high‐grade cervical precancer. We performed a systematic review and meta‐analysis of HPV persistence patterns worldwide. Medline and ISI Web of Science were searched through January 1, 2010 for articles estimating HPV persistence or duration of detection. Descriptive and meta‐regression techniques were used to summarize variability and the influence of study definitions and characteristics on duration and persistence of cervical HPV infections in women. Among 86 studies providing data on over 100,000 women, 73% defined persistence as HPV positivity at a minimum of two time points. Persistence varied notably across studies and was largely mediated by study region and HPV type, with HPV‐16, 31, 33 and 52 being most persistent. Weighted median duration of any‐HPV detection was 9.8 months. HR‐HPV (9.3 months) persisted longer than low‐risk HPV (8.4 months), and HPV‐16 (12.4 months) persisted longer than HPV‐18 (9.8 months). Among populations of HPV‐positive women with normal cytology, the median duration of any‐HPV detection was 11.5 and HR‐HPV detection was 10.9 months. In conclusion, we estimated that approximately half of HPV infections persist past 6 to 12 months. Repeat HPV testing at 12‐month intervals could identify women at increased risk of high‐grade cervical precancer due to persistent HPV infections.

Rate and predictors of new genital warts claims and genital warts-related healthcare utilization among privately insured patients in the United states

Background: Little non-clinic-based data are available on incident genital warts rates and related healthcare use. Goal: The goal of this study was to describe the incidence and predictors of genital warts and associated healthcare utilization patterns among a group of privately insured patients in the United States. Study: Health claims were evaluated prospectively from 5,914,107 privately insured individuals. Results: The rate of new genital warts claims per 100,000 person-years at risk, age-standardized to the 2001 U.S. privately insured population, increased from 117.8 in 1998 to 205.0 in 2001. The highest rates were among 20- to 29-year-olds. The majority of claims came from dermatology and obstetrics/gynecology. Conclusions: The incidence of genital warts, as measured by the rate of new claims, appears to be rising. Age associations with the rate of new genital warts claims differed by gender; these associations may be influenced by changes in health-seeking behavior, potentially driven by health awareness.