Long Fu Xi

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 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)

Prevalence of specific types of human papillomavirus and cervical squamous intraepithelial lesions in consecutive, previously unscreened, West-African women over 35 years of age†

Previous studies among women worldwide have demonstrated that infection with specific types of human papillomaviruses (HPV) is central to the pathogenesis of cervical neoplasia. There is little data, however, concerning the prevalence of specific HPV types and the association of each type with cervical neoplasia among women in sub‐Saharan Africa, who remain at very high risk of cervical cancer. We studied 2,065 consecutive patients aged 35 years or older, presenting to community health clinics in Dakar and Pikine, West Africa, who had not been screened previously for cytologic abnormalities or HPV. Cytologic diagnosis and HPV detection were accomplished using a ThinPrep Pap and a polymerase chain reaction‐based reverse‐line strip assay, respectively. Odds ratios (OR) and associated 95% confidence intervals (CI) were estimated using polynomial logistic regression. Cytologic abnormalities were found in 426 women (20%), including 254 (12%) with atypical squamous cells of undetermined significance, 86 (4%) with low‐grade squamous intraepithelial lesions, 66 (3%) with high‐grade squamous intraepithelial lesions (HSIL) and 20 (1%) with invasive cancer. HPV infection was detected in 18%. Among women with negative cytologic findings, the prevalence of high risk but not low risk HPV types increased with age. HPV16 (2.4%) and HPV58 (1.6%) were the most frequently detected HPV types in this population, as well as being the most strongly associated with risk of HSIL/cancer (HPV16: OR = 88, 95% CI = 39–200; HPV58: OR = 51, 95% CI = 16–161). These data suggest that in addition to HPV16, HPV58 should be considered in the strategic planning of vaccination against cervical cancer in this geographic region.

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.

Relationship between cigarette smoking and human papilloma virus types 16 and 18 DNA load.

Background: Although cigarette smoking has been associated with increased human papilloma virus (HPV) detection, its impact on HPV DNA load is unknown. Methods: The study subjects were women who were positive for HPV16 and/or HPV18 at enrollment into the Atypical Squamous Cells of Undetermined Significance–Low-grade Squamous Intraepithelial Lesion Triage Study. Assessments of exposure to smoke and sexual behavior were based on self-report. Viral genome copies per nanogram of cellular DNA were measured by multiplex real-time PCR. Linear or logistic regression models were used to assess the relationship between cigarette smoking and baseline viral load. Results: Of the 1,050 women (752 with HPV16, 258 with HPV18, and 40 with both HPV16 and HPV18), 452 (43.0%) were current smokers and 101 (9.6%) were former smokers at enrollment. The baseline viral load was statistically significantly greater for current compared with never smokers (P = 0.03 for HPV16; P = 0.02 for HPV18) but not for former smokers. Among current smokers, neither HPV16 nor HPV18 DNA load seemed to vary appreciably by age at smoking initiation, smoking intensity, or smoking duration. The results remained similar when the analysis of smoking-related HPV16 DNA load was restricted to women without detectable cervical abnormality. Conclusion: Higher baseline HPV16 and HPV18 DNA load was associated with status as a current but not former smoker. A lack of dose-response relationship between cigarette smoking and viral load may indicate a low threshold for the effect of smoking on HPV DNA load. (Cancer Epidemiol Biomarkers Prev 2009;18(12):3490–6)

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.

Viral Load in the Natural History of Human Papillomavirus Type 16 Infection: A Nested Case–control Study

BACKGROUND Viral load may influence the course of human papillomavirus type 16 (HPV-16) infection. METHODS This case-control study was nested within the 2-year Atypical Squamous Cells of Undetermined Significance and Low-Grade Squamous Intraepithelial Lesion Triage Study, in which women were followed semiannually for HPV and cervical intraepithelial neoplasia (CIN). Case patients (n = 62) were women diagnosed with CIN3 following HPV-16-positive detection at a follow-up visit. HPV-16-positive controls (n = 152) without CIN2 or CIN3 were matched to cases based on the follow-up visit in which viral load was measured. Real-time polymerase chain reaction was used for HPV-16 DNA quantification. RESULTS The risk of CIN3 increased with increasing HPV-16 DNA load at the follow-up visit (odds ratio, 1.63; 95% confidence interval, 1.33-1.99 per 1 log(10) unit increase); the association was not affected by whether HPV-16 was present at enrollment. When HPV-16 was present at both enrollment and follow-up, viral load remained high among cases (P = .77) but decreased substantially among controls (P = .004). Among women with HPV-16 found initially during follow-up, viral load in the first HPV-16-positive sample was associated with short-term persistence; load was higher in those with infection, compared with those without infection, 1 visit after the initial positivity (P = .001). CONCLUSIONS Viral load of newly detected infections and changes in viral load predict persistence and progression of HPV-16 infections.

Detection of Genital HPV Types in Fingertip Samples from Newly Sexually Active Female University Students

Background: Little is known about detection of genital human papilloma virus (HPV) types in womens fingertips. The study objectives were to determine the presence of genital HPV types in fingertip samples and the agreement between fingertip and genital samples for detecting HPV. Methods: At triannual visits, genital and fingertip samples were collected from female university students and tested for 37 HPV genotypes by PCR-based assay. Type-specific concordance between paired fingertip and genital samples was evaluated using κ statistics for percent positive agreement (κ+). Paired samples with type-specific concordant fingertip and genital results were selected for variant characterization. Results: A total of 357 fingertip samples were collected from 128 women. HPV prevalence in fingertip samples was 14.3%. Although percent positive agreement between fingertips and genitals for detecting type-specific HPV was low (17.8%; κ+ = 0.17; 95% confidence interval, 0.10-0.25), 60.4% of type-specific HPV detected in the fingertips was detected in a concurrent genital sample. All but one of 28 paired concordant samples were positive for the same type-specific variant in the fingertip and genital sample. Redetection of HPV types at the subsequent visit was more common in genital samples (73.3%) than in fingertip samples (14.5%; P < 0.001). Conclusions: Detection of genital HPV types in the fingertips was not uncommon. Although impossible to distinguish between deposition of DNA from the genitals to the fingertips and true fingertip infection, the rarity of repeat detection in the fingertips suggests that deposition is more common. Impact: Finger-genital transmission is plausible but unlikely to be a significant source of genital HPV infection. Cancer Epidemiol Biomarkers Prev; 19(7); 1682–5. ©2010 AACR.

Human Papillomavirus (HPV) type 16 and type 18 DNA Loads at Baseline and Persistence of Type-Specific Infection during a 2-year follow-up.

BACKGROUND Studies of viral load-associated persistence of human papillomavirus (HPV) infection are rare, with inconsistent results reported. METHODS The study subjects were 741 and 289 women who were positive for HPV type 16 (HPV-16) and HPV type 18 (HPV-18), respectively, at the time of enrollment into in the ASCUS-LSIL (Atypical Squamous Cells of Undetermined Significance-Low-Grade Squamous Intraepithelial Lesion) Triage Study and who returned 1 or more times for HPV testing during a biannual 2-year follow-up. The numbers of HPV-16 and HPV-18 copies per nanogram of cellular DNA at baseline were measured by use of real-time polymerase chain reaction. RESULTS Women with, compared with women without, persistent infection at month 6 of follow-up had a higher viral load at enrollment (P< .001, for HPV-16; P=.01, for HPV-18). The association of each 1-log(10) increase in viral load with persistence of HPV-16 or HPV-18 during the first 6 months of the study was statistically significant among women with multiple HPV types at enrollment (for HPV-16: odds ratio [OR], 1.53 [95% confidence interval {CI}, 1.29-1.82]; for HPV-18: OR, 1.35 [95% CI, 1.09-1.68]) but not among women with monotype infections (in tests assessing the interaction between viral load and coinfection, P=.002 for HPV-16 and P=.34 for HPV-18). Among women who continued to have positive results at month 6, 12, or 18, persistence of infection for another 6 months was unassociated with the viral load at baseline. CONCLUSION Prevalent infection with a higher viral load of HPV-16 or HPV-18 was associated with short- but not long-term persistence.

Effect of cervical cytologic status on the association between human papillomavirus type 16 DNA load and the risk of cervical intraepithelial neoplasia grade 3.

BACKGROUND Although correlations between cervical cytologic status and both human papillomavirus (HPV) load and histopathologic status are recognized, it is largely undetermined whether the association between the HPV DNA load and the risk of cervical intraepithelial neoplasia grade 3 (CIN-3) differs on the basis of cervical cytologic findings. METHODS Study subjects were 821 women enrolled in the ASCUS-LSIL Triage Study who tested positive for HPV-16 at entry. Women were followed semiannually for 2 years. The baseline HPV-16 load was measured by real-time polymerase chain reaction. RESULTS CIN-3 was confirmed in 286 (34.8%) of 821 women during the 2-year follow-up period. The adjusted odds ratio (OR) of the 2-year cumulative risk of CIN-3 was 1.46 (95% confidence interval [CI], 1.29-1.64) per 1 log(10) increase in virus load. The ORs varied from 1.66 (95% CI, 1.16-2.37) for women with normal cytologic findings at enrollment to 0.86 (95% CI, 0.61-1.20) for those with high-grade squamous intraepithelial lesions. Among women with normal cytologic findings at enrollment, the area under the receiver operating characteristic curve for detection of CIN-3 on the basis of the virus load was 0.70 (95% CI, 0.61-0.78). CONCLUSION The HPV-16 DNA load was associated with the risk of developing CIN-3, but the associations varied with cytologic findings at the time of virus load measurement. The clinical usefulness of measuring the HPV-16 load as a means to detect CIN-3 was minimal, even in women with normal cytologic findings.