Abstract 3439: Interaction between cutaneous human papillomavirus infection and telomere length in association with cutaneous squamous cell carcinoma

Abstract

Abstract Background: We previously reported that cutaneous human papillomavirus (HPV) infection was associated with significantly increased risk of cutaneous squamous cell carcinoma (SCC), while longer telomeres were associated with significantly reduced risk of SCC. We conducted further research to evaluate the interaction between cutaneous HPV and telomere length in association with SCC. Methods: Previously, a clinic based case-control (173 SCC cases and 300 controls) study was conducted, between 2007-2008, at the University of South Florida and Moffitt Cancer Center. HPV seropositivity (33 types) and DNA positivity (25 beta-HPV types) in eyebrow hairs (EB) and SCC tumors were measured using multiplex assays. Using quantitative PCR, relative telomere length was measured in peripheral blood leukocytes by determining the ratio of telomere repeat copy number to a single-copy gene copy number for each sample. For the present analyses, subjects with available data on telomere length and a) HPV serology (135 cases and 201 controls), b) HPV DNA in EB (130 SCC cases and 195 controls) and c) HPV DNA in SCC tumors (117 cases), were included. Association between telomere length and SCC was examined after stratification by HPV serostatus and HPV DNA status in EB, and odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression, adjusting for age and gender. Results: Telomere length did not differ significantly between beta-HPV seronegative (mean = 1.16, standard deviation (SD) = 0.57) and seropositive controls [mean (SD) = 1.24(0.75), P value = 0.56], or by tumor HPV DNA status (P value = 0.93). Longer telomere length was associated with significantly reduced risk of SCC among subjects seronegative to all HPV types or seropositive to a single beta1 HPV type (OR = 0.01, 95% CI = 0.001-0.10), while no association was observed among those seropositive to >1 beta1 HPV types (OR = 1.01, 95% CI = 0.95-1.07, Pinteraction = <0.0001). A significant interaction (Pinteraction = 0.0004) was also observed between telomere length and DNA positivity for > = 1 beta-HPV types in EB in association with SCC (OREB DNA negative = 0.003, 95% CI = <0.001-0.09; OREB DNA positive = 1.02, 95% CI = 0.98-1.06). Further, longer telomere length was associated with 62% (OR = 0.38, 95% CI = 0.19-0.75, Pinteraction = 0.004) and 55% (OR = 0.45, 95% CI = 0.23-0.90, Pinteraction = 0.01) reduced risk of SCC among subjects DNA negative for all beta-HPV types or positive for a single beta1 or beta2 type, respectively, while no associations were observed among those with EB DNA positivity for >1 beta1 or beta2 types (OR = 1.02, 95% CI = 0.98-1.07 for both groups). In summary, multiple beta-HPV infections showed significant statistical interaction with telomere length in association with SCC. Conclusion: Presence of cutaneous HPV infection may attenuate the protective effect of longer telomeres on the risk of SCC. Citation Format: Shalaka S. Hampras, Michael Pawlita, Massimo Tommasino, Jong Park, Pearlie K. Burnette, Neil A. Fenske, Basil A. Cherpelis, Dana E. Rollison. Interaction between cutaneous human papillomavirus infection and telomere length in association with cutaneous squamous cell carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3439.