Rachel L. Winer

Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: A meta-analysis update

Data on human papillomavirus (HPV) type distribution in invasive and pre‐invasive cervical cancer is essential to predict the future impact of HPV16/18 vaccines and HPV‐based screening tests. A meta‐analyses of HPV type distribution in invasive cervical cancer (ICC) and high‐grade squamous intraepithelial lesions (HSIL) identified a total of 14,595 and 7,094 cases, respectively. In ICC, HPV16 was the most common, and HPV18 the second most common, type in all continents. Combined HPV16/18 prevalence among ICC cases was slightly higher in Europe, North America and Australia (74–77%) than in Africa, Asia and South/Central America (65–70%). The next most common HPV types were the same in each continent, namely HPV31, 33, 35, 45, 52 and 58, although their relative importance differed somewhat by region. HPV18 was significantly more prevalent in adeno/adenosquamous carcinoma than in squamous cell carcinoma, with the reverse being true for HPV16, 31, 33, 52 and 58. Among HSIL cases, HPV16/18 prevalence was 52%. However, HPV 16, 18 and 45 were significantly under‐represented, and other high‐risk HPV types significantly over‐represented in HSIL compared to ICC, suggesting differences in type‐specific risks for progression. Data on HPV‐typed ICC and HSIL cases were particularly scarce from large regions of Africa and Central Asia.

Development and Duration of Human Papillomavirus Lesions, after Initial Infection

BACKGROUND To determine the potential value of human papillomavirus (HPV) vaccines, information concerning the incidence and duration of clinically important lesions is needed. METHODS A total of 603 female university students were followed for a mean duration of 38.8 months. Triannual gynecologic examinations included cervical and vulvovaginal specimen collection for Pap and HPV DNA testing. Women with cytologic evidence of a high-grade squamous intraepithelial lesion (SIL) were referred for colposcopically directed biopsy. RESULTS Among women with incident HPV infection, the 36-month cumulative incidence of cervical SILs found by cytologic testing (47.2%; 95% confidence interval [CI], 38.9%-56.4%) was higher than that of vaginal SILs (28.8%; 95% CI, 21.3%-38.2%). The median time to clearance of cervical and vaginal SILs was 5.5 and 4.7 months, respectively. Among women with incident HPV-16 or HPV-18 infection, the 36-month cumulative incidence of cervical intraepithelial neoplasia (CIN) grade 2 was 20.0% (95% CI, 10.8%-35.1%), and that of CIN grade 3 was 6.7% (95% CI, 2.5%-17.0%). The 36-month cumulative incidence of clinically ascertained genital warts among women with incident HPV-6 or HPV-11 infection was 64.2% (95% CI, 50.7%-77.4%). CONCLUSIONS Intraepithelial lesions are common early events among women with incident HPV infection, and the interval between incident HPV-16 or HPV-18 infection and biopsy-confirmed CIN grade 2-3 appears to be relatively short.

Genital Human Papillomavirus Infection in Men: Incidence and Risk Factors in a Cohort of University Students

BACKGROUND In contrast to the wealth of data on human papillomavirus (HPV) infections in women, much less is known about HPV in men. METHODS Between June 2003 and March 2006, a total of 240 heterosexually active male university students 18-20 years of age were recruited for participation in a cohort study of HPV infection. Genital cell samples were collected, at 4-month intervals, for HPV-DNA analysis by polymerase chain reaction. The subjects maintained a Web-based journal of sexual activity. RESULTS At 24 months, the cumulative incidence of new infection of any genital HPV type was 62.4% (95% confidence interval [CI], 52.6%-72.2%). Acquisition rates did not differ by genital site (i.e., glans, penile shaft, or scrotum) of initial detection (P=.86). The most commonly detected types were HPV-84 and HPV-16. In multivariate analysis, a report of a new sex partner during the prior 0-4 (hazards ratio [HR], 2.0 [95% CI, 1.3-3.0]) and 5-8 (HR, 1.8 [95% CI, 1.2-2.7]) months and a history of smoking (HR, 1.6 [95% CI, 1.1-2.4]) were associated with an elevated risk of HPV acquisition. CONCLUSION Genital HPV infection is common and multifocal in young men, and its incidence is higher than that reported for similar cohorts of young women. The high rates of HPV infection in men should be considered when strategies for the prevention of HPV infection in female adolescents and young women are being developed.

Risk of Female Human Papillomavirus Acquisition Associated with First Male Sex Partner

To quantify the risk of human papillomavirus (HPV) acquisition associated with a first male sex partner and to identify associated risk factors, we analyzed data from women who were enrolled before or within 3 months of first intercourse with a male partner and were censored at the report of a second partner. The 1-year cumulative incidence of first HPV infection was 28.5% (95% confidence interval, 20.6%-38.6%) and increased to almost 50% by 3 years. The risk was increased when the first male partner was sexually experienced. Our results indicate a high risk of HPV infection in young women who have had just 1 male sex partner.

Risk for High-Grade Cervical Intraepithelial Neoplasia Associated with Variants of Human Papillomavirus Types 16 and 18

Background: Although the variant lineages of human papillomavirus (HPV) types 16 and 18 are well established, their individual associations with high-grade cervical intraepithelial neoplasia (CIN) have not been extensively evaluated. Methods: Study subjects were women participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study who were positive for HPV16 or HPV18 at enrollment. These women were followed every 6 months for 2 years. Viral isolates from enrollment samples were characterized by DNA sequencing and classified as variant lineages. Results: Over a 2-year study period, CIN3 was histologically diagnosed in 291 of the 779 HPV16-positive women and 47 of the 275 HPV18-positive women. Among women without CIN2-3 at enrollment, the risk of subsequent CIN3 was 2.7-fold greater for those with HPV16 African-2 [95% confidence interval (95% CI), 1.0-7.0] and 3.1-fold greater for those with HPV16 Asian American (95% CI, 1.6-6.0), compared with European variants. Relative to infection with HPV18 African variants, the risk associating subsequent CIN3 was 3.8 (95% CI, 0.9-17.2) for infection with HPV18 European variants and 4.8 (95% CI, 1.0-23.6) for infection with HPV18 Asian American variants. Similar associations were observed when the 2-year prevalence of CIN3 was used as the end point. Further, for those with HPV16 European variants, the 2-year prevalence of CIN3 was higher in White women than in African American women (P = 0.01); this trend was reversed for those with HPV16 African-1 variants (P = 0.22). A similar pattern was present for infections with HPV18 European versus African variants. Conclusions: The lineages of HPV16 and HPV18 variants are associated with differing risks for high-grade CIN. (Cancer Epidemiol Biomarkers Prev 2007;16(1):4–10)

From the NIH: proceedings of a workshop on the importance of self-obtained vaginal specimens for detection of sexually transmitted infections.

On June 27, 2006, the NIH conducted a workshop to review published data and current field practices supporting the use of self-obtained vaginal swabs (SOVs) as specimens for diagnosis of sexually transmitted infections (STIs). The workshop also explored the design of studies that could support FDA clearance of SOVs for STI testing, particularly for specimens collected in nonclinical settings including patients’ homes. This report summarizes the workshop findings and recommendations. Participants concluded that self-obtained vaginal swabs are well accepted by women of all ages and that SOVs perform as well as or better than other specimen types for Chlamydia trachomatis and Neisseria gonorrhoeae detection using transcription-mediated amplification. In addition, workshop participants recommended the validation of SOV testing by public health practitioners and manufacturers of STI diagnostic tests to expedite incorporation of SOVs as a diagnostic option in clinical and nonclinical settings for Chlamydia trachomatis and Neisseria gonorrhoeae testing. Similarly, SOVs should be explored for use in the diagnosis of other sexually transmitted pathogens.

Early Natural History of Incident, Type-Specific Human Papillomavirus Infections in Newly Sexually Active Young Women

Background: Characterizing short-term detection patterns of young womens incident α-genus human papillomavirus (HPV) infections may further our understanding of HPV transmission. Methods: Between 2000 and 2007, we followed 18- to 22-year-old female university students with triannual HPV DNA and Papanicolaou testing. Using Kaplan–Meier methods, we estimated duration of detectable, type-specific incident infections; time to redetection (among infections that became undetectable); and time to cervical lesion development after incident infection. We evaluated risk factors for short-term persistent versus transient infection with logistic regression. Results: Three hundred three incident, type-specific infections were detected in 85 sexually active women. Median time to first negative test after incident infection was 9.4 (95% CI: 7.8–11.2) months; 90.6% of infections became undetectable within 2 years. About 19.4% of infections that became undetectable were redetected within 1 year. Cervical lesions were common and 60% were positive for multiple HPV types in concurrent cervical swabs. Incident HPV detection in the cervix only (vs. the vulva/vagina only or both sites) was associated with short-term transience. Conclusions: Although most incident infections became undetectable within 2 years, redetection was common. Cervical lesions were a common early manifestation of HPV infection. Impact: It remains unclear whether potentially modifiable risk factors can be identified to reduce infection duration (and transmission likelihood). Cancer Epidemiol Biomarkers Prev; 20(4); 699–707. ©2011 AACR.

Persistence of Genital Human Papillomavirus Infection in a Long-Term Follow-Up Study of Female University Students

BACKGROUND Little is known about the epidemiology of human papillomavirus (HPV) infections that persist for more than a few years. METHODS Four to 12 years after participation in a longitudinal study of incident HPV infection, a cohort of former university students returned for a follow-up visit that included HPV genotyping of cervical and vulvovaginal swab specimens and collection of colposcopy-directed biopsy specimens. RESULTS Of 147 women with HPV infection detected during their undergraduate years, 24 (16.3%) were positive for 1 or more of the same HPV types at follow-up. Overall, 27 (4.8%) of 567 type-specific HPV infections persisted, and DNA sequence analyses of a subset revealed that all were variant specific. Long-term HPV persistence was positively associated with frequent but sporadic detection of the same HPV type early during the course of the infection and with abnormal Pap tests and genital warts; it was negatively associated with marriage and was not associated with the number of intercurrent sex partners. CONCLUSIONS HPV variant and behavioral risk factor analyses indicated that long-term detection of the same HPV type was more consistent with viral persistence than with reinfection. Although long-term persistence was not common, it was associated with detection of HPV-related pathologies.

Concordance of self-collected and clinician-collected swab samples for detecting human papillomavirus DNA in women 18 to 32 years of age

Objective: The objective of this study was to determine whether self- and clinician-collected samples are comparable for human papillomavirus (HPV) detection. Study Design: Three hundred seventy-four women aged 23 to 32 (population 1) and 211 women aged 18 to 25 (population 2) contributed self-collected vaginal and clinician-collected cervical and vulvovaginal samples for HPV DNA testing. Eighty-six women mailed in self-collected samples. Results: Agreement between self-collected vaginal and clinician-collected combined cervical/vulvovaginal samples was excellent (population 1:92.0%, &kgr; = 0.81; population 2: 96.4%, &kgr; = 0.88), but self-collected samples were more concordant with clinician-collected cervical samples in population 2 (&kgr; = 0.84) than population 1 (&kgr; = 0.65) (P = 0.01). Age-adjusted HPV prevalence was slightly lower in mailed-in (21.5%) than in-clinic self-collected samples (26.8%). Conclusions: The combined clinician-collected cervical/vulvovaginal sample is most sensitive for detecting all female genital tract HPV infections. HPV concordance between cervical and vaginal samples may be better for newer infections. Larger studies are needed to determine whether mailed-in self-samples are as effective as those collected in a clinical setting.

Serum Antibody Response Following Genital α9 Human Papillomavirus Infection in Young Men

Background. Although the prevalence of human papillomavirus (HPV) genital infection is similarly high in males and females, seroprevalence is lower in males. This study assessed rates and determinants of seroconversion after detection of genital HPV infection in young men. Methods. We investigated HPV type-specific seroconversion in a cohort of heterosexual male university students who had an α9 HPV type (HPV-16, -31, -33, -35, -52, -58, or -67) detected in the genital tract (n = 156). HPV DNA and antibodies were detected and typed using liquid bead-based multiplex assays. We calculated seroconversion using Kaplan-Meier survival analysis. Cox proportional hazards models with generalized estimating equations were used to examine associations with seroconversion. Results. Within 24 months of detecting genital HPV infection, type-specific seroconversion ranged from 4% for HPV-52 to 36% for HPV-31. HPV-16 seroconversion at 24 months was 13% (95% confidence interval [CI], 7%-25%). Among incident HPV infections, ever cigarette smoking and infection site(s) (shaft/scrotum and glans/urine vs shaft/scrotum or glans/urine only) were positively associated with type-specific seroconversion. Conclusions. For each of the α9 HPV types, type-specific seroconversion within 24 months was observed in 36% or less of infected men. Seroconversion might be related to cigarette smoking and genital site(s) infected.