Abstract IA-15: Serum testosterone and estradiol modify risk of anal HPV16/18 infections but only estradiol and Estrogen Receptor 1-alpha influences risk for histological high-grade squamous intraepithelial lesions (HSIL)

Abstract

Abstract Background: We reported higher serum free testosterone (FT) and anal-HPV16/18 infection prevalence in MSM. Associations between serum-FT and -estradiol, anal-HPV16/18 infections, and Estrogen Receptor 1α (ESR1) and histological HSIL (hHSIL) are unclear. Methods: Three serial cross-sectional analyses were performed using data for 489 HIV-infected/HIV-uninfected adult males enrolled in the Multicenter AIDS Cohort Study. For 340, anal cytology residuals were evaluated for 37 HPVs (PCR). For 214 men, 336 HRA/biopsies were evaluated for hHSIL; among them, <3 biopsy specimens for 47% (102) were assessed for ESR1 using immunohistochemistry. Serum specimen collection preceded HPV and HRA/biopsy visits by 24(+9) months. Each specimen was tested for Sex Hormone Binding Globulin (radioimmunoassay), and total testosterone and estradiol (TE2) (Liquid chromatography/mass spectrometry); serum-FT (pg/mL) was estimated. HPVs were classified: HPV16/18+, other Group-1 and -2 high-risk HPVs+ (hrHPVs); low-risk HPVs+ (lrHPVs), and none. Biopsies were evaluated as hHSIL vs. <hHSIL. Formalin-fixed paraffin-embedded anal biopsy (~4μm) were prepared and stained using a standard ESR1 immunohistochemistry protocol and were scored for immunofluorescence (0-3+) and percent affected (0-100%) by two pathologists. Multivariable-adjusted GEE logistic regression models assessed relationships between loge-transformed FT, TE2 and ESR1 (%), and HPV16/18+ and hHSIL separately. Self-reported sociodemographic/behavioral covariates were included. Results: Adjusted estimates showed higher FT increased odds of HPV16/18-infection (OR=1.87 (1.2-2.92)), but odds were inversely associated with TE2 (OR=0.68(0.49-0.94)). White race and other Group-1-hrHPVs+ increased odds for HPV16/18 infection (OR=2.61(1.16-5.87) and (OR=1.65(1.11-2.46)), but neither HIV-infection/CD4+count, receptive anal intercourse partnerships; exogenous-testosterone use, nor smoking increased HPV16/18-infection odds. Serum-TE2 and hHSIL were inversely associated (OR=0.51(0.3-0.89)) Serum-FT was not associated with odds of hHSIL (OR=1.09(0.78-1.74)), but. men testing HPV16/18+ showed higher odds of hHSIL than hrHPV-negative men (OR=4.27(1.71-10.66)). Median IHC ER1α-expression intensity was lower among hHSIL affected men: 10% (hHSIL) vs. 40% (<hHSIL). The percent of immunofluorescence intensity (%) was inversely associated with odds of hHSIL (OR=0.96(0.93-0.99). Conclusions: Higher serum-FT increased odds of anal HPV16/18-infection but not hHSIL. Higher serum-TE2 was inversely associated with the odds of both HPV16/18+ and hHSIL, and ESR1 expression in tissue is lower in hHSIL- than <hHSIL-affected epithelium. More research evaluating sex hormones and ERα expression in stroma and epithelial cells of HPV-associated HSIL/<HSIL-affected tissue is needed. Citation Format: Dorothy J. Wiley. Serum testosterone and estradiol modify risk of anal HPV16/18 infections but only estradiol and Estrogen Receptor 1-alpha influences risk for histological high-grade squamous intraepithelial lesions (HSIL) [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr IA-15.