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Background Women living with HIV (WLWH) experience high rates of anal cancer. Screening using anal cytology, high-resolution anoscopy (HRA) with biopsies, can histologically diagnose anal cancer precursors called high-grade squamous intraepithelial lesions (HSIL). The low specificity of screening using anal cytology results in HRA referral for many WLWH without HSIL. Screening using high-risk human papillomavirus (HR-HPV) may improve specificity. Methods Two hundred seven WLWH (63% non-Hispanic black) were screened for anal histologic HSIL (hHSIL) using cytology, HRA-guided biopsies, and Xpert HPV. Xpert performance for predicting anal hHSIL was compared with that of cytology. Usng Xpert 5 HPV genotypic results and accompanying cycle thresholds, receiver operator characteristic curve and recursive partitioning analyses were used to create predictive models for hHSIL. Results The performance of Xpert to predict hHSIL was not different from that of cytology with a sensitivity (Sn) of 89% and specificity (Sp) of 49%. Interpretation of Xpert was modified using genotypic results and receiver operator characteristic curve analysis, which produced a screen with an Sn and Sp of 75% and 84% for hHSIL, respectively. Another reinterpretation of Xpert was created using recursive partitioning and cycle thresholds, which predicted hHSIL with an Sn and Sp of 75% and 86%, respectively. The detection of HPV-16 was highly predictive of hHSIL in all analyses. These modified screening tests would reduce HRA referral in this population by almost half compared with anal cytology. Conclusions Xpert HPV is an alternative to anal cytology to screen for anal HSIL and can be optimized to reduce the number of unnecessary HRAs performed in WLWH.

Background Although declining rates of incident AIDS-related Kaposi sarcoma (KS) have been reported, KS incidence rates have noted race/ethnic, age, and geographic diversity. We performed a comprehensive assessment of recent secular trends in AIDS-related KS incidence in the United States. Methods We identified incident KS diagnosed in men aged 20-54 years (who comprise most AIDS-related KS in the United States) using the US Cancer Statistics registry data. Joinpoint analysis assessed for trends in age-adjusted incidence rates between 2000 and 2014 calculating average annual percentage changes (AAPCs) with 95% confidence intervals. Heat maps were generated to compare age-adjusted HIV incidence rates with KS incidence rates. Results Age-adjusted KS incidence rates nationwide decreased from 1.44/100,000 to 0.95/100,000 between 2000 and 2014. Observed rate changes varied across subgroups; eg, there were significant decreases in 30-44 years (AAPC = -5.4%), particularly in Whites and Blacks, significant increases among 20-29 years (AAPC = 2.7), primarily in Blacks, and stable rates among 45-54 years (AAPC = -0.03). In Southern United States, the incidence rates among Blacks did not significantly change. The states with highest average age-adjusted rates over the study period were Georgia (2.71/100,000), New York (2.16/100,000), California (2.02/100,000), Florida (1.90/100,000), and Texas (1.39/100,000), with significantly decreasing trends over time, except Georgia where rates increased (AAPC = 1.8). Conclusions Although KS incidence rates have decreased nationally, age, racial, and geographic disparities persist, including increasing risk among younger Black men and particularly elevated rates in some southern states and urban areas. Further research is needed to address racial and geographic AIDS-related KS disparities.

BACKGROUND: Protease inhibitors (PIs) may inhibit Kaposi sarcoma (KS) carcinogenesis. However, PI-based antiretroviral therapy (ART) is rarely a first-line choice in people living with HIV (PLWH) because of cost and toxicities. This is the first systematic review to assess KS incidence stratified by ART type. METHODS: We searched PubMed to identify original, full research reports of KS incidence in ART-treated adult PLWH, stratified by ART class, published between 1996 and 2017. For overlapping cohorts, we included only the most recent study and supplemented data with earlier relevant analyses. We described study design, sociodemographic characteristics, statistical adjustment factors, and KS incidence. RESULTS: We identified three unique retrospective cohort studies, and supplemented one of the studies with results from six prior subgroup reports, which included 242,309 PLWH and 3570 incident KS cases. Overall, KS crude incidence decreased by a factor of 10 between untreated and ART-treated PLWH; CD4-adjusted KS incidence decreased by ~50%, with either non-nucleoside reverse transcriptase inhibitor (NNRTI)- or PI-based ART. A single study measured a cumulative dose-/time-dependent effect of ART, which reported a relative risk reduction in only the cohort receiving boosted PI-based ART. Other studies defined ART categories by first-line therapy only. CONCLUSIONS: The risk of incident KS was significantly reduced regardless of ART class even after adjusting for CD4 count. The quality of evidence (i.e., most studies categorizing users by first-line ART) does not permit KS risk reduction comparisons across ART types. Given the limited number and retrospective nature of these studies, prospective data is indicated.

BACKGROUND Recent studies have shown that the incidence of squamous cell cancer of the anus (SCCA) has increased in the combined antiretroviral therapy (cART) era. The effect of undetectable HIV viral loads as a result of successful cART has not been evaluated. METHODS We performed a retrospective cohort study among male US veterans diagnosed with HIV and followed between 1985 and 2009 using the Veterans Affairs Immunologic Case Registry (VA-ICR). We calculated age-adjusted incidence rates and rate ratios for SCCA. We conducted Cox proportional hazards ratios of SCCA in a multivariable model including time-varying covariates of nadir CD4 count and overall percentage of time with an undetectable HIV viral load. RESULTS The age-adjusted SCCA incidence rate among the group who ever received cART was 146.8/100,000 person-years (95% confidence interval, 124.1 to 172.6) and was not significantly higher than the SCCA rate of those who never received cART (134.3/100,000 person-years; 95% confidence interval, 112.5 to 159.0). In a multivariable model limited to veterans who had ever received cART (adjusted for demographic variables, nadir, and most recent CD4 counts) individuals who had 61%-80% or 81%-100% of follow-up time with undetectable HIV viral loads had significantly decreased SCCA risk compared with those who had undetectable HIV viral loads

Squamous cell carcinoma of the anal canal (SCCA) is etiologically linked to human papillomavirus, and its incidence is increased among the immunosuppressed. We used data from the Surveillance, Epidemiology, and End Results program to analyze the incidence of SCCA in relation to 3 separate periods during the HIV epidemic: the pre-HIV era (1973-1981), the HIV era (1982-1995), and the highly active antiretroviral treatment (HAART) era (1996-2001). The incidence per 100,000 population of SCCA increased from 0.6 in the pre-HIV era to 0.8 in the HIV era and to 1.0 in the HAART era. The gap in SCCA incidence between women and men decreased from a ratio of 1.6:1 in the pre-HIV era to 1.5:1 in the HIV era and to 1.2:1 in the HAART era. There was a significant increase in incidence rates among men and women aged 30 to 54 years in the HAART era compared with the HIV era. Men were more likely to be diagnosed with early-stage disease, but they were less likely than women to receive radiation therapy. The incidence of SCCA has particularly increased among men and those between 30 and 54 years of age since the introduction of HAART.