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Anal Human Papillomavirus Infection in Women and Its Relationship with Cervical Infection

Human papillomavirus (HPV), the primary cause of cervical cancer, is also associated with the development of anal cancer. Relatively little is known about the epidemiology of anal HPV infection among healthy females and its relationship to cervical infection. We sought to characterize anal HPV infection in a cohort of adult women in Hawaii. Overall, 27% (372 of 1,378) of women were positive for anal HPV DNA at baseline compared with 29% (692 of 2,372) with cervical HPV DNA. Among women with paired anal and cervical samples, anal infection without accompanying cervical infection was observed in 14% (190 of 1,363). Concurrent anal and cervical HPV infections were observed in 13% (178 of 1,363) of women. Women with cervical HPV infection had >3-fold increased risk of concurrent anal infection. Concurrent anal and cervical HPV infection was most prevalent among the youngest women and steadily decreased through age 50 years. By contrast, the prevalence of anal infection alone remained relatively steady in all age groups. Compared with cervical infections, the overall distribution of HPV genotypes in the anus was more heterogeneous and included a greater proportion of nononcogenic types. A high degree of genotype-specific concordance was observed among concurrent anal and cervical infections, indicating a common source of infection. Nevertheless, the association of anal intercourse with anal HPV infection was limited to those women without accompanying cervical infection. The relationship of anal to cervical infection as described in this study has implications for the development of anal malignancies in women.

Circumcision and Human Papillomavirus Infection in Men: A Site-Specific Comparison

BACKGROUND Lack of circumcision has been identified as a risk factor for male genital human papillomavirus (HPV) infection, although this association has not been consistently supported. METHODS Specimens for HPV testing were collected from a cohort of 379 (primarily heterosexual) adult males. HPV prevalence in the glans penis and coronal sulcus, penile shaft, scrotum, semen, and urine was compared by circumcision status. RESULTS Overall, HPV DNA prevalence ranged from 6% in semen to 52% in the penile shaft. The prevalence of any HPV infection in the glans/corona was significantly higher in uncircumcised men (46%) than in circumcised men (29%) (odds ratio [OR], 1.96 [95% confidence interval (CI), 1.02-3.75], adjusted for demographic characteristics and sexual history). Uncircumcised men also had an increased risk of oncogenic HPV infection (adjusted OR, 2.51 [95% CI, 1.11-5.69]) and infection with multiple HPV types (adjusted OR, 3.56 [95% CI, 1.50-8.50]). Among uncircumcised men, HPV prevalence in the foreskin (44%) was comparable to that in the glans/corona, and type-specific positivity was observed between the 2 sites (kappa=0.52). CONCLUSIONS Uncircumcised men have an increased risk of HPV infection, including with oncogenic HPV, specifically localized to the glans/corona, possibly because of its proximity to the foreskin, which may be particularly vulnerable to infection.

Prevalence, Acquisition, and Clearance of Cervical Human Papillomavirus Infection among Women with Normal Cytology: Hawaii Human Papillomavirus Cohort Study

Few natural history studies of cervical human papillomavirus (HPV) incidence and duration have been conducted among older women, especially from multiethnic populations. Viral and nonviral determinants of HPV acquisition and clearance were examined among 972 sexually active women, ages 18 to 85 years, recruited from clinics on Oahu, Hawaii, and followed for a mean duration of 15 months (range, 2-56 months). Interviews and cervical cell specimens for cytology and HPV DNA detection by PCR, using the PGMY09/PGMY11 primer system, were obtained at baseline and at 4-month intervals. The prevalence of cervical HPV infection was 25.6% at study entry. A total of 476 incident genotype-specific infections were observed during the follow-up period. The incidence of high-risk (HR) HPV types (9.26 per 1,000 woman-months) was similar to low-risk (LR) HPV types (8.24 per 1,000 woman-months). The most commonly acquired HR-HPV types were HPV-52, HPV-16, and HPV-31; and their incidence was increased significantly with a coexisting cervical HPV infection. Cervical HPV acquisition decreased with age, income, and long-term use of oral contraceptives and increased with number of sexual partners, use of hormonal creams, alcohol drinking, and condom use by a sexual partner. Cohort participants cleared 265 of the 476 incident infections during follow-up. LR-HPV infections cleared more rapidly than did HR-HPV infections (median, 180 days versus 224 days). Clearance times were enhanced among older women and women with multiple infections. Our data suggest several viral and nonviral determinants of cervical HPV acquisition and clearance that might be used in cervical cancer prevention programs.

Acquisition of Anal Human Papillomavirus (HPV) Infection in Women: the Hawaii HPV Cohort Study

BACKGROUND The majority of anal cancer is associated with human papillomavirus (HPV) infection, yet little is known about womens risk of acquisition of anal HPV infection. METHODS Risk factors for the acquisition of anal HPV infection were examined in a longitudinal cohort study of 431 women, via repeated measurement of HPV DNA. RESULTS Seventy percent of women were positive for anal HPV infection at one or more clinic visits from baseline through a follow-up period that averaged 1.3 years. The incidence of a high-risk (HR) infection was 19.5 (95% confidence interval [CI], 16.0-23.6) per 1000 woman-months. The most common incident HR HPV types were HPV-53, -52 and -16. The presence of an HR anal HPV infection at baseline increased the risk of an incident anal infection by 65%. Baseline HR cervical HPV infection also predicted the acquisition of an HR anal HPV infection (odds ratio, 1.81 [95% CI, 1.09-3.02]). Nonviral risk factors for acquisition of HR HPV infection included younger age, lower socioeconomic status, greater lifetime number of sexual partners, past use of hormones, and condom use. CONCLUSIONS The results of this study suggest that womens risk of anal HPV infection is as common as their risk of cervical HPV infection.

Sequential Acquisition of Human Papillomavirus (HPV) Infection of the Anus and Cervix: The Hawaii HPV Cohort Study

BACKGROUND Relatively little is known about the epidemiology of anal human papillomavirus (HPV) infection in healthy women and its association with cervical HPV infection. METHODS he association of an incident cervical (or anal) HPV infection with the subsequent risk of a genotype-concordant incident anal (or cervical) HPV infection was examined in a longitudinal cohort study of 751 sexually active women. Age-adjusted hazard ratios, obtained using Cox regression, served as measurements of relative risk (RR). RESULTS Among women, the RR of acquiring an anal HPV infection after a cervical infection with HPV of the same genotype was 20.5 (95% confidence interval, 16.3-25.7), and the RR of acquiring a cervical HPV infection after an anal infection with HPV of the same genotype was 8.8 (95% confidence interval, 6.4-12.2), compared with women without a previous anal/cervical infection with HPV of a concordant genotype. RRs varied by phylogenetic species, with HPV alpha3/alpha15 and alpha1/alpha8/alpha10 types having a greater likelihood than other types of HPV infecting the anus among women with a previous infection at the cervix with HPV of the same genotype. CONCLUSIONS It appears common for anal and cervical HPV infections to occur consecutively. The high degree of genotype-specific concordance suggests that the cervix (vagina) and anus may serve as reservoirs for HPV infection at the other anatomical site.

Duration and Clearance of Anal Human Papillomavirus (HPV) Infection among Women: The Hawaii HPV Cohort Study

BACKGROUND The association of anal cancer with human papillomavirus (HPV) infection is well established; however, little is known about the epidemiology of anal HPV in healthy women. We investigated patterns of duration and clearance of anal HPV infection in a cohort of healthy women in Hawaii. METHODS Viral and nonviral determinants of anal HPV clearance were examined in a longitudinal cohort study of 431 sexually active women. At baseline and at 4-month intervals, interviews were conducted and cervical and anal cell specimens were obtained for detection of HPV DNA. RESULTS Of the 431 women, 50% experienced a total of 414 incident anal HPV infections, reported at 1 clinic visits from baseline through a follow-up period of average duration of 1.2 years. Of these infections, 58% cleared during follow-up. The clearance rate for a high-risk anal infection was 9.2 per 100 woman-months (95% confidence interval [CI], 6.9-11.9 per 100 woman-months), with a median duration of 150 days (95% CI, 132-243 days). The slowest clearing high-risk HPV types were HPV-59 (median clearance time, 350 days) and HPV-58 (median clearance time, 252 days). The median clearance times for HPV-16 and HPV-18, the predominant types associated with anal cancer, were 132 days and 212 days, respectively. Nonviral factors that delayed clearance of anal HPV included douching, long-term tobacco smoking, and anal sex. CONCLUSIONS The majority of anal HPV infections resolve in a relatively short time. Although anal HPV is commonly acquired in healthy women, its rapid clearance suggests limited efficacy of HPV testing as an anal cancer screening tool.

Comparison of Physician- and Self-Collected Genital Specimens for Detection of Human Papillomavirus in Men

ABSTRACT There is currently no consensus regarding the most appropriate methods of sampling for the detection of genital human papillomavirus (HPV) in men. We employed a recently developed collection method involving abrasion and moistened swabbing of the genital skin surface for the detection of HPV in a cohort of 136 university-affiliated males in Hawaii. Genital specimens collected by physicians using this method were compared with self-collected specimens from the same individuals obtained 24 h later. Self-collected specimens yielded a greater proportion of sufficient specimens than physician-collected specimens. HPV detection was comparable in physician- and self-collected specimens; detection was highest in the penile shaft (51.2% and 51.5%, respectively, P = 0.96), followed by the scrotum (41.2% and 46.2%, P = 0.43), the glans/coronal sulcus (31.9% and 33.1%, P = 0.84), and the foreskin (33.3% and 28.6%, P = 0.74). Site-specific agreement in HPV detection between paired physician- and self-collected samples ranged from 67.2% (kappa = 0.34) for the penile shaft to 95.0% (kappa = 0.89) for the foreskin. There was a high degree of concordance in HPV genotypes in HPV-positive pairs. The most common type was HPV type 84, which comprised approximately 15% of the specimens. The emery paper-swab method offers an efficient sampling method for genital HPV DNA detection in men that could be used both within and outside of the clinical setting.

Reduced Clearance of Penile Human Papillomavirus Infection in Uncircumcised Men

The relationship between circumcision and the acquisition and clearance of human papillomavirus (HPV) infection was examined in a cohort of 357 men followed up at 2-month intervals for an average of 431 days. There were no differences in HPV acquisition by circumcision status. Clearance of HPV infection, including infection with oncogenic types, was slower in the glans/coronal sulcus of the penis of uncircumcised men than circumcised men. The median duration of HPV infection of the glans/coronal sulcus was significantly longer in uncircumcised men (154 days) than circumcised men (91 days) (P=.04). Circumcision may protect against HPV-associated disease by enhancing the resolution of infection.

Hawaii Cohort Study of Serum Micronutrient Concentrations and Clearance of Incident Oncogenic Human Papillomavirus Infection of the Cervix

The degree to which the resolution of human papillomavirus (HPV) infection parallels exposure to other factors, particularly those related to nutritional status, is a relatively unexplored area of research. We established a cohort of women for long-term follow-up to examine the association of serum retinol, carotenoid, and tocopherol concentrations with the clearance of incident cervical HPV infection. Interviews and biological specimens were obtained at baseline and at 4-month intervals. At each visit, a cervical cell specimen for HPV DNA analysis and cytology and a fasting blood sample to measure micronutrient levels were collected. A Cox proportional hazards model was used to study the relationship between clearance of 189 incident (type-specific) oncogenic HPV infections and the levels of 20 serum micronutrients among 122 women. Higher circulating levels of trans-zeaxanthin, total trans-lutein/zeaxanthin, cryptoxanthin (total and beta), total trans-lycopene and cis-lycopene, carotene (alpha, beta, and total), and total carotenoids were associated with a significant decrease in the clearance time of type-specific HPV infection, particularly during the early stages of infection (<or=120 days). HPV clearance time was also significantly shorter among women with the highest compared with the lowest serum levels of alpha-tocopherol and total-tocopherol, but significant trends in these associations were limited to infections lasting <or=120 days. Clearance of persistent HPV infection (lasting >120 days) was not significantly associated with circulating levels of carotenoids or tocopherols. Results from this investigation support an association of micronutrients with the rapid clearance of incident oncogenic HPV infection of the uterine cervix.