Anne F. Rositch

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.

Increased age and race-specific incidence of cervical cancer after correction for hysterectomy prevalence in the United States from 2000 to 2009.

Invasive cervical cancer is thought to decline in women over 65 years old, the age at which cessation of routine cervical cancer screening is recommended. However, national cervical cancer incidence rates do not account for the high prevalence of hysterectomy in the United States.

Contributions of recent and past sexual partnerships on incident human papillomavirus detection: acquisition and reactivation in older women

Understanding the fraction of newly detected human papillomavirus (HPV) infections due to acquisition and reactivation has important implications on screening strategies and prevention of HPV-associated neoplasia. Information on sexual activity and cervical samples for HPV DNA detection using Roche Linear Array were collected semiannually for two years from 700 women ages 35 to 60 years. Incidence and potential fraction of HPV associated with new and lifetime sexual partnerships were estimated using Poisson regression. Cox frailty models were used to estimate hazard ratios (HR) for potential risk factors of incident HPV detection. Recent and lifetime numbers of sexual partners were both strongly associated with incident HPV detection. However, only 13% of incident detections were attributed to new sexual partners, whereas 72% were attributed to 5 or more lifetime sexual partners. Furthermore, 155 of 183 (85%) incident HPV detections occurred during periods of sexual abstinence or monogamy, and were strongly associated with cumulative lifetime sexual exposure [HR: 4.1, 95% confidence interval (CI): 2.0-8.4). This association increased with increasing age. These data challenge the paradigm that incident HPV detection is driven by current sexual behavior and new viral acquisition in older women. Our observation that most incident HPV infection was attributable to past, not current, sexual behavior at older ages supports a natural history model of viral latency and reactivation. As the more highly exposed baby-boomer generation of women with sexual debut after the sexual revolution transition to menopause, the implications of HPV reactivation at older ages on cervical cancer risk and screening recommendations should be carefully evaluated.

Incidence and progression of cervical lesions in women with HIV: A systematic global review

Global data on cervical lesion incidence and progression in HIV-positive women are essential for understanding the natural history of cervical neoplasia and informing screening policy. A systematic review was performed summarizing the incidence and progression of cervical lesions in HIV-positive women. Of 5882 HIV-positive women from 15 studies, incidence ranged from 4.9 to 21.1 cases per 100 woman-years for any cervical lesion and 0.4 to 8.8 cases per 100 woman-years for high-grade cervical lesions. HIV-positive women showed a median three-fold higher incidence of cervical lesions compared to HIV-negative women. Of 1099 HIV-positive women from 11 studies, progression from low- to high-grade lesions ranged from 1.2 to 26.2 cases per 100 woman-years. Both incidence and progression rates increased with lower CD4 counts. The effect of antiretroviral therapy on the natural history of cervical neoplasia remains unclear. HIV-positive women have higher incidence and progression of cervical neoplasia. Cervical cancer screening should be integrated into HIV treatment programmes.

A Cohort Effect of the Sexual Revolution May Be Masking an Increase in Human Papillomavirus Detection at Menopause in the United States

BACKGROUND Cohort effects, new sex partnerships, and human papillomavirus (HPV) reactivation have been posited as explanations for the bimodal age-specific HPV prevalence observed in some populations; no studies have systematically evaluated the reasons for the lack of a second peak in the United States. METHODS A cohort of 843 women aged 35-60 years were enrolled into a 2-year, semiannual follow-up study. Age-specific HPV prevalence was estimated in strata defined by a lower risk of prior infection (<5 self-reported lifetime sex partners) and a higher risk of prior infection (≥ 5 lifetime sex partners). The interaction between age and lifetime sex partners was tested using likelihood ratio statistics. Population attributable risk (PAR) was estimated using Levins formula. RESULTS The age-specific prevalence of 14 high-risk HPV genotypes (HR-HPV) declined with age among women with <5 lifetime sex partners but not among women with ≥ 5 lifetime sex partners (P = .01 for interaction). The PAR for HR-HPV due to ≥ 5 lifetime sex partners was higher among older women (87.2%), compared with younger women (28.0%). In contrast, the PAR associated with a new sex partner was 28% among women aged 35-49 years and 7.7% among women aged 50-60 years. CONCLUSIONS A lower cumulative probability of HPV infection among women with a sexual debut before the sexual revolution may be masking an age-related increase in HPV reactivation in the United States.

Knowledge and Acceptability of Pap Smears, Self-Sampling and HPV Vaccination among Adult Women in Kenya

Objectives Our study aimed to assess adult women’s knowledge of human papillomavirus (HPV) and cervical cancer, and characterize their attitudes towards potential screening and prevention strategies. Methods Women were participants of an HIV-discordant couples cohort in Nairobi, Kenya. An interviewer-administered questionnaire was used to obtain information on sociodemographic status, and sexual and medical history at baseline and on knowledge and attitudes towards Pap smears, self-sampling, and HPV vaccination at study exit. Results Only 14% of the 409 women (67% HIV-positive; median age 29 years) had ever had a Pap smear prior to study enrollment and very few women had ever heard of HPV (18%). Although most women knew that Pap smears detect cervical cancer (69%), very few knew that routine Pap screening is the main way to prevent ICC (18%). Most women reported a high level of cultural acceptability for Pap smear screening and a low level of physical discomfort during Pap smear collection. In addition, over 80% of women reported that they would feel comfortable using a self-sampling device (82%) and would prefer at-home sample collection (84%). Nearly all women (94%) reported willingness to be vaccinated to prevent cervical cancer if offered at no or low cost. Conclusions These findings highlight the need to educate women on routine use of Pap smears in the prevention of cervical cancer and demonstrate that vaccination and self-sampling would be acceptable modalities for cervical cancer prevention and screening.

Hysterectomy-corrected cervical cancer mortality rates reveal a larger racial disparity in the United States.

The objectives of this study were to determine the age‐standardized and age‐specific annual US cervical cancer mortality rates after correction for the prevalence of hysterectomy and to evaluate disparities by age and race.

Knowledge, attitudes, practices, and perceived risk of cervical cancer among kenyan women brief report

Objectives Eastern Africa has the highest incidence and mortality rates from cervical cancer worldwide. It is important to describe the differences among women and their perceived risk of cervical cancer to determine target groups to increase cervical cancer screening. Methods In this cross-sectional study, we surveyed women seeking reproductive health services in Kisumu, Kenya to assess their perceived risk of cervical cancer and risk factors influencing cervical cancer screening uptake. χ2 statistics and t tests were used to determine significant factors, which were incorporated into a logistic model to determine factors independently associated with cervical cancer risk perception. Results Whereas 91% of the surveyed women had heard of cancer, only 29% of the 388 surveyed women had previously heard of cervical cancer. Most had received their information from health care workers. Few women (6%) had ever been screened for cervical cancer and cited barriers such as fear, time, and lack of knowledge about cervical cancer. Nearly all previously screened women (22/24 [92%]) believed that cervical cancer was curable if detected early and that screening should be conducted annually (86%). Most women (254/388 [65%]) felt they were at risk for cervical cancer. Women with perceived risk of cervical cancer were older (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02–1.10), reported a history of marriage (OR, 2.08; CI, 1.00–4.30), were less likely to feel adequately informed about cervical cancer by health care providers (OR, 0.76; CI, 0.18–0.83), and more likely to intend to have cervical cancer screening in the future (OR, 10.59; CI, 3.96–28.30). Only 5% of the women reported that they would not be willing to undergo screening regardless of cost. Conclusions Cervical cancer is a major health burden for women in sub-Saharan Africa, yet only one third of the women had ever heard of cervical cancer in Kisumu, Kenya. Understanding factors associated with women’s perceived risk of cervical cancer could guide future educational and clinical interventions to increase cervical cancer screening.

Multiple Human Papillomavirus Infections and Type Competition in Men

BACKGROUND There is little information on multiple human papillomavirus (HPV) infections and the potential for type competition in men, yet competition may impact the type-specific efficacy of HPV vaccination. METHODS Among 2702 uncircumcised men in Kisumu, Kenya, who were seronegative for human immunodeficiency virus, the observed numbers of HPV types detected were compared with the expected number, which was simulated under the assumption of independent infections. To assess the potential for HPV type competition, adjusted odds ratios for pairwise combinations of prevalent HPV type infections were estimated using semi-Bayesian methods. RESULTS Half of all men were HPV positive, of whom 57% had multiple HPV types. We observed men without HPV infection and with ≥4 HPV types more often than expected if infections were independent. No negative associations between individual HPV types were observed. HPV types 31, 39, 56, 58, and 59 were positively associated with both carcinogenic vaccine types HPV-16 and HPV-18 (2-sided P value <.05). CONCLUSIONS Men who were HPV infected were likely to test positive for >1 HPV type. Cross-sectional associations between individual HPV types were positive and did not appear to be type-specific. Thus, we did not identify HPV types that are candidates for potential HPV type competition in men.

Barriers to antiretroviral initiation in HIV-1-discordant couples.

BackgroundIn Kenya and much of sub-Saharan Africa, nearly half of all couples affected by HIV are discordant. Antiretroviral therapy (ART) slows disease progression in HIV-1–infected individuals and reduces transmission to uninfected partners. We examined time to ART initiation and factors associated with delayed initiation in HIV-1–discordant couples in Nairobi. MethodsHIV-1–discordant couples were enrolled and followed quarterly for up to 2 years. Clinical staff administered questionnaires and conducted viral loads and CD4 counts. Participants with a CD4 count meeting ART criteria were referred to a nearby US Presidents Emergency Plan for AIDS Relief–funded treatment center. Barriers to ART initiation among participants with a CD4 count eligible for ART were assessed by Cox regression. ResultsOf 439 HIV-1–infected participants (63.6% females and 36.4% males), 146 met CD4 count criteria for ART during follow-up. Median time from meeting CD4 criteria until ART initiation was 8.9 months, with 42.0% of eligible participants on ART by 6 months and 63.4% on ART by 1 year. The CD4 count at the time of eligibility was inversely associated with time to ART initiation (hazard ratio = 0.49, P < 0.001). Compared with homeowners, those paying higher rents started ART 48% more slowly (P = 0.062) and those paying lower rents started 71% more slowly (P = 0.002). ConclusionsDespite access to regular health care, referrals to treatment centers, and free access to ART, over one-third of participants with an eligible CD4 count had not started ART within 1 year. Factors of lower socioeconomic status may slow ART initiation, and targeted approaches are needed to avoid delays in treatment initiation.