Objective

The primary cervical cancer screening strategy for women over age 30 is high-risk human papillomavirus (HPV) testing combined with Papanicolaou (Pap) testing (cotesting) every 5 years. This combination strategy is a preventive service that is required by the Affordable Care Act to be covered with no cost-sharing by most health insurance plans. The cotesting recommendation was made based entirely on prospective data from an insured population that may have a lower proportion of women with HPV positive and Pap negative results (ie, discordant results). The discordant group represents a very difficult group to manage. If the frequency of discordant results among underserved women is higher, health care providers may perceive the cotesting strategy to be a less favorable screening strategy than traditional Pap testing every 3 years.

Study design

The Centers for Disease Control and Prevention's Cervical Cancer Study was conducted at 15 clinics in 6 federally qualified health centers across Illinois. Providers at these clinics were given the option of cotesting for routine cervical cancer screening. Type-specific HPV detection was performed on residual extracts using linear array.

Results

Pap test results were abnormal in 6.0% and HPV was positive in 7.2% of the underserved women screened in this study (mean age, 45.1 years). HPV prevalence decreased with age, from 10.3% among 30- to 39-year-olds to 4.5% among 50- to 60-year-olds. About 5% of the women had a combination of a positive HPV test and normal Pap test results; HPV 16/18 was identified in 14% of discordant women.

Conclusion

The rate of discordant results among underserved women was similar to those reported throughout the US in a variety of populations. Typing for HPV 16/18 appears to assist in the management in a small proportion of women with discordant results.

Objective

The aim of this study is to compare colposcopic findings and the accuracy of colposcopic impression in HIV seropositive and seronegative women with abnormal Pap tests.

Methods

HIV seropositive and seronegative women in a national cohort study had Pap tests collected every six months, with colposcopy for any abnormal result. Prospectively collected colposcopy and histology findings were analyzed retrospectively using Pearson Chi-square, t-test and Wilcoxon two-sample tests, logistic regression models, and Kappa coefficients.

Results

After adjusting for age and Pap result, 1618 eligible HIV seropositive women were more likely than 406 seronegative women to have inadequate colposcopic examinations, abnormal colposcopic findings, and large cervical lesions. However, among those with abnormal colposcopy, colposcopic characteristics and lesion size and number did not differ by HIV serostatus. Agreement between colposcopists' impressions and highest grade biopsy diagnoses was fair (kappa coefficient 0.35, 95% C.I. 0.31, 0.38). Agreement did not differ by HIV serostatus and did not improve with multiple biopsies (weighted kappa coefficient 0.35, 95% C.I. 0.32, 0.39) or after including all histology results over two years following colposcopy.

Conclusion

Although HIV seropositive women with abnormal cytology are more likely to have colposcopic abnormality, the performance of colposcopy appears to be similar to that in HIV seronegative women. Biopsy is required to confirm colposcopic impression.

To estimate the incidence of invasive cervical cancer (ICC) across up to 21 years of follow-up among women with human immunodeficiency virus (HIV) and to compare it to that among HIV-uninfected women, we reviewed ICC diagnoses from a 20-year multi-site U.S. cohort study of HIV infected and uninfected women who had Pap testing every 6 months. Incidence rates were calculated and compared to those in HIV-negative women. Incidence ratios standardized to age-, sex-, race-, and calendar-year specific population rates were calculated. After a median follow-up of 12.3 years, four ICCs were confirmed in HIV seropositive women, only one in the last 10 years of observation, and none in seronegative women. The ICC incidence rate did not differ significantly by HIV status (HIV seronegative: 0/100,000 person-years vs. HIV seropositive: 19.5/100,000 person-years; p = 0.53). The standardized incidence ratio for the HIV-infected WIHS participants was 3.31 (95% CI: 0.90, 8.47; p = 0.07). Although marginally more common in women without HIV, for those with HIV in a prevention program, ICC does not emerge as a major threat as women age.

Objective

The aim of this study is to compare colposcopic findings and the accuracy of colposcopic impression in HIV seropositive and seronegative women with abnormal Pap tests.

Methods

HIV seropositive and seronegative women in a national cohort study had Pap tests collected every six months, with colposcopy for any abnormal result. Prospectively collected colposcopy and histology findings were analyzed retrospectively using Pearson Chi-square, t-test and Wilcoxon two-sample tests, logistic regression models, and Kappa coefficients.

Results

After adjusting for age and Pap result, 1618 eligible HIV seropositive women were more likely than 406 seronegative women to have inadequate colposcopic examinations, abnormal colposcopic findings, and large cervical lesions. However, among those with abnormal colposcopy, colposcopic characteristics and lesion size and number did not differ by HIV serostatus. Agreement between colposcopists' impressions and highest grade biopsy diagnoses was fair (kappa coefficient 0.35, 95% C.I. 0.31, 0.38). Agreement did not differ by HIV serostatus and did not improve with multiple biopsies (weighted kappa coefficient 0.35, 95% C.I. 0.32, 0.39) or after including all histology results over two years following colposcopy.

Conclusion

Although HIV seropositive women with abnormal cytology are more likely to have colposcopic abnormality, the performance of colposcopy appears to be similar to that in HIV seronegative women. Biopsy is required to confirm colposcopic impression.

Objectives

We investigated whether the effect of smoking on the incidence of smoking-related cancers differs by HIV-infection status, if sex modifies the impact of risk factors for smoking-related cancers, and the sex-specific attributable risk of smoking on cancer incidence.

Design

Data from two large prospective studies in the United States were analyzed: 6789 men in the Multicenter AIDS Cohort Study from 1984 through 2018 and 4423 women in the Women's Interagency HIV Study from 1994 through 2018.

Methods

Incidence rates, relative risks, and adjusted population attributable fractions (PAFs) were calculated for smoking-related cancers.

Results

During study follow-up, there were 214 incident smoking-related cancers in the men and 192 in the women. The age-adjusted incidence ratess for smoking-related cancers were higher in the women (392/100 000) than for the men (198/100 000; P < 0.01) and higher for people living with HIV (PLWH, 348/100 000) than for those without HIV (162/100 000; P < 0.01). Unadjusted incidence rates in PLWH were higher than in those without HIV when stratifying by cumulative pack-years of smoking (all P values <0.01). In adjusted interaction models, the effects of cumulative pack-years of smoking were significantly stronger in women. The adjusted PAFs for smoking-related cancers were nonsignificantly higher in the women than in the men (39 vs. 28%; P = 0.35).

Conclusion

HIV looks to be an independent risk factor for smoking-related cancers and women appear to have a greater risk than men. These results highlight the need for interventions to help PLWH, especially women, quit smoking and sustain cessation to reduce their risk of smoking-related cancers.

To estimate the incidence of invasive cervical cancer (ICC) across up to 21 years of follow-up among women with human immunodeficiency virus (HIV) and to compare it to that among HIV-uninfected women, we reviewed ICC diagnoses from a 20-year multi-site U.S. cohort study of HIV infected and uninfected women who had Pap testing every 6 months. Incidence rates were calculated and compared to those in HIV-negative women. Incidence ratios standardized to age-, sex-, race-, and calendar-year specific population rates were calculated. After a median follow-up of 12.3 years, four ICCs were confirmed in HIV seropositive women, only one in the last 10 years of observation, and none in seronegative women. The ICC incidence rate did not differ significantly by HIV status (HIV seronegative: 0/100,000 person-years vs. HIV seropositive: 19.5/100,000 person-years; p = 0.53). The standardized incidence ratio for the HIV-infected WIHS participants was 3.31 (95% CI: 0.90, 8.47; p = 0.07). Although marginally more common in women without HIV, for those with HIV in a prevention program, ICC does not emerge as a major threat as women age.

Objective

To estimate the accuracy of Pap testing for women who are human immunodeficiency virus (HIV)-seropositive, with a focus on negative predictive value.

Methods

Participants in the Women's Interagency HIV Study were monitored with conventional Pap tests every 6 months. After excluding those with abnormal Pap test results before study, cervical disease, or hysterectomy, women with negative enrollment Pap test results were monitored for development of precancer within 15 or 39 months, defined as a Pap test result read as high-grade squamous intraepithelial lesion, atypical glandular cells favor neoplasia, or adenocarcinoma in situ, or a cervical biopsy read as cervical intraepithelial neoplasia 2 or worse. Correlations between one or more consecutive negative Pap test results and subsequent precancer were assessed using Cox proportional hazards models.

Results

Among 942 HIV-infected women with negative baseline Pap test results, eight (1%) developed precancer within 15 months and 40 (4%) within 39 months. After three consecutive negative Pap test results, precancer was rare, with no cases within 15 months and 10 of 539 (2%) within 39 months. No women developed precancer or cancer within 39 months after 10 consecutive negative Pap test results. Risks for precancer within 15 months after negative Pap test result included current smoking (adjusted hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.2-2.0 compared with nonsmokers), younger age (adjusted HR 1.5, 95% CI 1.1-2.1 for women aged younger than 31 years compared with older than 45 years), and lower CD4 count (adjusted HR 11.8, 95% CI 1.3-2.3 for CD4 200-500/microliter, adjusted HR 2.2, 95% CI 1.6-2.9 for CD4 less than 200/microliter, compared with CD4 more than 500/microliter).

Conclusion

Annual Pap testing appears safe for women infected with HIV; for those with serial negative tests, longer intervals are appropriate.

Level of evidence

II.

To estimate the long term cumulative risk for cervical intraepithelial neoplasia grade 3 or worse after an abnormal cervical Pap test and to assess the effect of HIV infection on that risk. Participants in the Women's Interagency HIV Study were followed semiannually for up to 10 years. Pap tests were categorized according to the 1991 Bethesda system. Colposcopy was prescribed within 6 months of any abnormality. Risk for biopsy-confirmed CIN3 or worse after abnormal cytology and at least 12 months follow-up was assessed using Kaplan-Meier curves and compared using log-rank tests. Risk for CIN2 or worse was also assessed, since CIN2 is the threshold for treatment. After a median of 3 years of observation, 1,947 (85%) women subsequently presented for colposcopy (1,571 [81%] HIV seropositive, 376 [19%] seronegative). CIN2 or worse was found in 329 (21%) of HIV seropositive and 42 (11%) seronegative women. CIN3 or worse was found in 141 (9%) of seropositive and 22 (6%) seronegative women. In multivariable analysis, after controlling for cytology grade HIV seropositive women had an increased risk for CIN2 or worse (H.R. 1.66, 95% C.I 1.15, 2.45) but higher risk for CIN3 or worse did not reach significance (H.R. 1.33, 95% C.I. 0.79, 2.34). HIV seropositive women with abnormal Paps face a marginally increased and long-term risk for cervical disease compared to HIV seronegative women, but most women with ASCUS and LSIL Pap results do not develop CIN2 or worse despite years of observation.

Background

HIV-seropositive women face high risk for infection with oncogenic human papillomavirus (oncHPV) types, abnormal Pap test results, and precancer, but cervical cancer risk is only modestly increased. Human papillomavirus (HPV)16 is highly oncogenic but only weakly associated with HIV status and immunosuppression, suggesting HPV16 may have a greater innate ability to evade host immune surveillance than other oncHPV types, which in turn should result in a greater relative increase in the prevalence of other oncHPV types among women with cervical precancer.

Objective

We sought to assess whether the underrepresentation of HPV16 among HIV-seropositive relative to HIV-seronegative women remains among those with cervical precancers.

Study design

HIV-seropositive and HIV-seronegative women in the Women's Interagency HIV Study were screened for cervical intraepithelial neoplasia (CIN) grade ≥3 (CIN3(+)). DNA from >40 HPV types was detected by polymerase chain reaction in cervicovaginal lavage specimens obtained at the visit at which CIN3(+) was diagnosed.

Results

HPV16 was detected in 13 (62%) of 21 HIV-seronegative women with CIN3(+) but only 44 (29%) of 154 HIV-seropositive women with CIN3(+) (P = .01). The lower prevalence of HPV16 in CIN3(+) among HIV-seropositive women persisted after controlling for covariates (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.08-0.78). The prevalence of other members of the HPV16-related alpha-9 oncHPV clade as a group was similar in HIV-infected and uninfected women with CIN3(+) (OR, 1.02; 95% CI, 0.53-1.94). The prevalence of non-alpha-9 oncHPV types was increased in HIV-seropositive vs HIV-seronegative women with CIN3(+) (OR, 3.9; 95% CI, 1.3-11.8).

Conclusion

The previously demonstrated increase in CIN3(+) incidence among HIV-seropositive women is associated with lower HPV16 and higher non-alpha-9 oncHPV prevalence. This is consistent with prior reports that HIV has a weak effect on infection by HPV16 relative to other oncHPV and supports use of nonavalent HPV vaccine in HIV-seropositive women.

Objective

Vaginal cancer is an uncommon cancer of the lower genital tract, and standardized screening is not recommended. Risk factors for vaginal cancer include a history of other lower genital tract neoplasia or cancer, smoking, immunosuppression, and exposure to diethylstilbestrol in utero. Although cervical cancer screening after total hysterectomy for benign disease is not recommended, many women inappropriately undergo vaginal cytology and/or human papillomavirus (hrHPV) tests, and clinicians are faced with managing their abnormal results. Our objective is to review the literature on vaginal cytology and hrHPV testing and to develop guidance for the management of abnormal vaginal screening tests.

Methods

An electronic search of the PubMed database through 2015 was performed. Articles describing vaginal cytology or vaginal hrHPV testing were reviewed, and diagnostic accuracy of these tests when available was noted.

Results

The available literature was too limited to develop evidence-based recommendations for managing abnormal vaginal cytology and hrHPV screening tests. However, the data did show that 1) the risk of vaginal cancer in women after hysterectomy is extremely low, justifying the recommendation against routine screening, and 2) in women for whom surveillance is recommended, e.g. women post-treatment for cervical precancer or cancer, hrHPV testing may be useful in identification of vaginal cancer precursors.

Conclusion

Vaginal cancer is rare, and asymptomatic low-risk women should not be screened. An algorithm based on expert opinion is proposed for managing women with abnormal vaginal test results.