Abstract

Background and objectivesHuman papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) is increasing globally. In Taiwan, HPV-positive OPSCC is obscured by tobacco, alcohol, and betel quid use. We investigated the role of high-risk HPV (hrHPV) in a large retrospective Taiwan OPSCC cohort.Methods and resultsThe cohort of 541 OPSCCs treated at Chang Gung Memorial Hospital from 1998–2016 consisted of 507 men (94%) and 34 women (6%). Most used tobacco (81%), alcohol (51%), and betel quid (65%). Formalin-fixed, paraffin-embedded tissue was used for p16 staining (a surrogate marker for HPV) and testing for HPV DNA presence and type by Multiplex HPV PCR-MassArray. HPV DNA and/or p16 staining (HPV-positive) was found in 28.4% (150/528) tumors. p16 and HPV DNA were strongly correlated (F < 0.0001). HPV16 was present in 82.8%, and HPV58 in 7.5% of HPV-positive tumors. HPV was associated with higher age (55.5 vs. 52.7 years, p = 0.004), lower T-stage (p = 0.008) better overall survival (OS) (hazard ratio [HR] 0.58 [95% CI 0.42–0.81], p = 0.001), and disease-free survival (DFS) (HR 0.54 [95% CI 0.40–0.73], p < 0.0001). Alcohol was strongly associated with recurrence and death (OS: HR 2.06 [95% CI 1.54–2.74], p < 0.0001; DFS: HR 1.72 [95% CI 1.33–2.24], p < 0.0001). OS and DFS in HPV-positive cases decreased for alcohol users (p < 0.0001). Obscured by the strong alcohol effect, predictive associations were not found for tobacco or betel quid.ConclusionsAs with HPV-positive OPSCC globally, HPV is an increasingly important etiological factor in Taiwanese OPSCC. HPV-positive OPSCC has considerable survival benefit, but this is reduced by alcohol, tobacco, and betel quid use. hrHPV is a cancer risk factor in males and females. Vaccinating both sexes with a multivalent vaccine including HPV58, combined with alcohol and tobacco cessation policies will be effective cancer-prevention public health strategies in Taiwan.

Highlights

  • The occurrence of oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing in North America and Western Europe, accounting for approximately 100,000 new cases worldwide each year [1,2,3]

  • Human papillomavirus (HPV) was associated with higher age (55.5 vs. 52.7 years, p = 0.004), lower tumor stage (T-stage) (p = 0.008) better overall survival (OS), and disease-free survival (DFS) (HR 0.54 [95% CI 0.40–0.73], p < 0.0001)

  • HPV-positive OPSCC has considerable survival benefit, but this is reduced by alcohol, tobacco, and betel quid use. high-risk HPV (hrHPV) is a cancer risk factor in males and females

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Summary

Introduction

The occurrence of oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing in North America and Western Europe, accounting for approximately 100,000 new cases worldwide each year [1,2,3]. High-risk human papillomavirus (hrHPV), HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, and 73, has become the leading etiologic factor of OPSCC [2,20,21,22,23,24,25,26,27,28]. Countries in Western Europe have observed similar trends [7,13,36,37,39,40,41] These changes have been accompanied by an increment in the survival rates for OPSCC [36,42,43]. Human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma (OPSCC) is increasing globally. We investigated the role of high-risk HPV (hrHPV) in a large retrospective Taiwan OPSCC cohort

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