Introduction: Taiwan has a high rate of oropharyngeal squamous cell carcinoma (OPSCC). The etiologic factors are primarily tobacco and alcohol abuse. High-risk human papillomaviruses (hrHPV) have been reported in oral cancers in Taiwan, but their role in oropharyngeal cancer has not been studied. We investigated the possible role of hrHPV in OPSCC Taiwanese patients.

Materials and Methods: We identified 546 OPSCC tumors from patients undergoing standard care and informed consent, between 1998 and 2016, at the Chang Gung Memorial Hospital (CGMH) in Taiwan. Formalin-fixed, paraffin-embedded (FFPE) tissue sections from 504 patients were screened by p16 immunostaining, a surrogate marker for active HPV (Ventana antibody, Cat. No. 725-4713, prediluted), and scored for intensity and proportion of positive tumor cells according to the 2018 College of American Pathologists recommendations. Genomic DNA was extracted from FFPE sections (AllPrep Kit, Qiagen) and HPV was detected and genotyped by Multiplex PCR-Mass Array (PCR-MA) analysis designed to detect 15 high-risk, 1 intermediate-risk, and 2 low-risk HPV types.

Results: Of the 504 OPSCC tumors tested for p16, 104 (20.6%) were positive, 380 (75.4%) negative, and 20 (4.0%) could not be scored. Spearman nonparametric correlation analysis demonstrated a linear increase in p16 positivity with time from 1998 to 2015 in this Taiwanese population (r= 0.6320, p= 0.003; R2= 0.4901, p= 0.0012). To date, HPV genotyping in 179 Taiwan tumors showed that 38 (21.2%) were hrHPV positive, 120 (67.0%) negative, and 21 (11.7%) had insufficient DNA. Of the 38 HPV-positive tumors, HPV16 alone was found in 31 (81.6%), HPV39 and HPV59 were each found once in separate tumors, and several tumors had two HPV types present: HPV16 and HPV18 were present together in 2 tumors, and each of the following pairs were found in one tumor each: HPV16 with HPV35, HPV16 with HPV59, and HPV16 with HPV6. Of the tumors tested by both p16 and PCR-MA, there was 97% concordance between the results (130/134).

Conclusion: Our preliminary findings indicate that the proportion of hrHPV positive OPSCC tumors in this Taiwanese population is increasing over the period from 1998 to 2015 in Taiwan. The concordance of p16 and HPV DNA is very high (p<0.0001), demonstrating that the hrHPV in the tumors is transcriptionally active and likely is an etiologic factor in the majority of OPSCC patients treated at CGMH in the past 18 years. This is consistent with the increasing role of hrHPV in OPSCC in Western countries and may reflect changing socioeconomic trends in Taiwan.

Citation Format: Guadalupe Lorenzatti Hiles, Chun-I Wang, Lisa M. Pinatti, Christine M. Goudsmit, Lila Peters, Hannah L. Briggs, Trey B. Thomas, Mohammed Charara, Reem A. Khatib, Macy A. Afsari, Anna C. Morris, Nadine Jawad, Devraj Som, Kai-Ping Chang, Thomas E. Carey, Heather M. Walline. High-risk human papillomavirus association with oropharyngeal squamous cell carcinoma in Taiwan [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B07.