Papillomavirus Research (Jun 2018)
Serum testosterone and estradiol modify risk of anal HPV16/18 infections but only estradiol influences risk for histological high-grade squamous intraepithelial lesions (HSIL)
Abstract
Background: We reported higher serum free testosterone (FT) and increased anal-HPV16/18 infection prevalence in MSM. Associations between serum-FT and -estradiol and anal-HPV16/18 infections and histological HSIL (hHSIL) are unclear. Methods: Two cross-sectional analyses were performed. 340 HIV-infected/HIV-uninfected Multicenter AIDS Cohort MSM were tested for anal HPVs; another 214 men were evaluated using HRA/biopsy with multiple assessments for some totaling 336 HRAs. Serum specimens collection preceded HPV and HRA visits by 24(+9) months and were tested for albumin, SHBG (radioimmunoassay), and total testosterone and estradiol (TE2) (LC/MS); serum-FT (pg/mL) was estimated. Anal swabs were tested for 37 HPVs (PCR) and classified: HPV16/18+, other Group-1 and -2 high-risk HPVs+ (hrHPVs); low-risk HPVs+ (lrHPVs), vs. none. Biopsies were evaluated as hHSIL vs. <hHSIL. Multivariable-adjusted GEE logistic regression models assessed relationships between loge-transformed FT and TE2, and HPV16/18+ and hHSIL, separately. Sociodemographic/behavioral covariates were included. Results: Adjusted estimates showed higher FT increased odds of HPV16/18-infection (OR=1.9 (1.2–2.9)), 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=2.6 (1.2–5.9) and (OR=1.7 (1.1–2.5)), but neither HIV-infection/CD4+count, receptive anal intercourse partnerships; exogenous-testosterone nor tobacco use increased HPV16/18-infection odds. Serum-FT was not associated with odds of hHSIL (OR=1.1 (0.7, 1.8)), but serum-TE2 and hHSIL was: OR=0.5 (0.3, 0.9). Men testing HPV16/18+ alone showed higher odds of hHSIL than hrHPV-negative men (OR=4.3 (1.7, 10.7)). Conclusions: Higher serum-FT increased odds of anal HPV16/18-infection but not hHSIL. Consistent across both analyses, and unexpectely, higher serum-TE2 lowered odds of both HPV16/18+ and hHSIL in these MSM.