L Stewart Massad

Case-Control Study of Cervicovaginal β/γ–Human Papillomavirus Infection in Women With Human Immunodeficiency Virus and Its Relation to Incident Cervical Precancer

Abstract We studied cervicovaginal β/γ–human papillomavirus (HPV) and their relationship to cervical precancer in women with human immunodeficiency virus; having previously reported strong positive associations of β/γ-HPV with incident head and neck cancer in the general population. Case patients (n = 124) had cervical intraepithelial neoplasia (CIN) 3 or 2. Controls (n = 247) were individually matched 2:1 to case patients. Unexpectedly, multivariate analyses found strong inverse associations between β/γ-HPV and CIN-2/3 (odds ratio, 0.19 [95% confidence interval, .04–.86]; P = .03; Ptrend < .01]). This is, to our knowledge, the first study of β/γ-HPV and cervical precancer. If confirmed, a strong inverse (protective) association would be of potential clinical and biologic relevance.

Epidemiological evidence that common HPV types may be common because of their ability to evade immune surveillance: Results from the Women's Interagency HIV study

Infection by human papillomavirus (HPV) type 16, the most oncogenic HPV type, was found to be the least affected by HIV‐status and CD4 count of any of the approximately 13 oncogenic HPV types. This relative independence from host immune status has been interpreted as evidence that HPV16 may have an innate ability to avoid the effects of immunosurveillance. However, the impact of immune status on other individual HPV types has not been carefully assessed. We studied type‐specific HPV infection in a cohort of 2,470 HIV‐positive (HIV[+]) and 895 HIV‐negative (HIV[−]) women. Semi‐annually collected cervicovaginal lavages were tested for >40 HPV types. HPV type‐specific prevalence ratios (PRs), incidence and clearance hazard ratios (HRs), were calculated by contrasting HPV types detected in HIV[+] women with CD4 < 200 to HIV[−] women. HPV71 and HPV16 prevalence had the weakest associations with HIV‐status/CD4 count of any HPV, according to PRs. No correlations between PRs and HPV phylogeny or oncogenicity were observed. Instead, higher HPV type‐specific prevalence in HIV[−] women correlated with lower PRs (ρ = −0.59; p = 0.0001). An alternative (quadratic model) statistical approach (PHIV+ = a*PHIV− + b*PHIV−2; R2 = 0.894) found similar associations (p = 0.0005). In summary, the most prevalent HPV types in HIV[−] women were the types most independent from host immune status. These results suggest that common HPV types in HIV[−] women may have a greater ability to avoid immune surveillance than other types, which may help explain why they are common.

Frequency of high-grade squamous cervical lesions among women over age 65 years living with HIV

Current US cervical cancer screening guidelines recommend screening cessation at the age of 65 years provided women have adequate previous screening and no history of precancer. Women living with HIV are at higher risk of cervical cancer than women living without HIV. Furthermore, limited data exists to quantify the risk of cervical cancer among women who otherwise would qualify for screening cessation. This study aimed to determine whether guidelines recommending women to discontinue cervical cancer screening at the age of 65 years are appropriate for women living with HIV. Semiannual Papanicolaou testing was performed as part of surveillance visits in the Women's Interagency HIV Study. Launched in October 1994, the Women's Interagency HIV Study is a federally funded US multisite cohort study that has enrolled 3678 women living with HIV and 1304 women living without HIV; we included data throughout September 2019 onward. Conventional Papanicolaou tests were collected at scheduled 6-month visits and read centrally according to the 1991 Bethesda System criteria. Results were analyzed among women at least 65 years of age. The primary endpoint was high-grade cytology, including high-grade squamous intraepithelial lesions; atypical glandular cells; atypical squamous cells, cannot exclude high-grade lesions; and malignant cytology. Wilcoxon rank-sum tests were used to compare the continuous variables, and Chi-square tests or the Fisher exact tests were used to compare the categorical variables. The Kaplan-Meier method was used to calculate the cumulative incidence. Poisson regression was used to compare 2 incidence rates. Of 169 eligible women (121 women living with HIV and 48 women living without HIV) who contributed 678.4 person-years of observation after reaching the age of 65 years, 2.2% had high-grade cytologic abnormalities. However, no cancer was found. Furthermore, 20 women had previous precancer results, and 74 women had abnormal Papanicolaou test results in the previous decade. Among 50 women (38 women living with HIV and 12 women living without HIV) with a previous hysterectomy and no history of cervical precancer, the cumulative incidence rates of high-grade squamous intraepithelial lesions were 0.6 (95% confidence interval, 0.0-3.2) per 100 person-years for women living with HIV and 0.0 (95% confidence interval, 0.0-8.1) per 100 person-years for women living without HIV (P=.61). Only 48 women (27 women living with HIV and 21 women living without HIV) had cervices and met the current guidelines to discontinue screening; their risk of experiencing high-grade squamous intraepithelial lesions was 2.2 (95% confidence interval, 0.6-5.5) per 100 person-years overall and did not vary by HIV status (2.3 [95% confidence interval, 0.5-6.8] per 100 person-years for women living with HIV and 1.8 [95% confidence interval, 0.0-9.8] per 100 person-years for women living without HIV; P=.81). Most women living with HIV do not meet the criteria for cervical cancer screening cessation and will need to continue screening over the age of 65 years; however, women who meet the criteria for screening cessation have risks of high-grade squamous lesions similar to women living without HIV and may choose to discontinue.

Impacts of the COVID‐19 pandemic on cervical cancer will be severe

Linked article: This is a mini commentary on Jennifer M. Davies et al., pp. 1133–1139 in this issue. To view this article visit https://doi.org/10.1111/1471-0528.17098