Understanding the impact of high-risk human papillomavirus on oropharyngeal squamous cell carcinomas in Taiwan: A retrospective cohort study

Abstract

Background and objectives Human 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 results The 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. Conclusions As 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.

Rising incidence of HPV positive oropharyngeal cancer in Taiwan between 1999 and 2014 where betel nut chewing is common

“…This study also explores the incidence trend of HPV positive OPC in a population where HPV negative head and neck cancer is still prevalent. Similar to previous studies, this study shows that the percentage of HPV positive OPC remained stable around 30% for each calendar periods [ 8 – 12 ] but both incidences of HPV negative OPC and HPV positive OPC are rapidly increasing by about two folds in Taiwan during the period from 1999 to 2014. This low percentage may be one of the reasons why some clinicians do not think that HPV positive OPC is an important head and neck cancer in Taiwan despite the increasing number of HPV positive OPC patients in recent years.…”

“…In fact, our findings revealed that the percentage of HPV positive OPC in Northern Taiwan (33%), where it is more urbanized with higher prevalence of HPV infection and lower prevalence of betel nut chewing [ 16 , 22 ], is higher than that in other regions (22.5%) and rose from 25 to 38% during the period of 1999–2014. This trend is similar to another single hospital-based cohort in Northern Taiwan [ 12 ]. This suggests that the percentage of HPV positive OPC will rise and surpass HPV negative OPC, becoming a common head and neck cancer in the near future.…”

“…This is the first study on estimating the incidence trend of HPV positive OPC using primary tumor tissue obtained from multiple hospitals in Taiwan. Previous studies estimated incidence trend of HPV positive OPC using tumor tissue from a single hospital without time trend analysis [ 8 – 12 ] or nationwide data analysis without tumor tissue study [ 20 ]. This study also explores the incidence trend of HPV positive OPC in a population where HPV negative head and neck cancer is still prevalent.…”

“…In Taiwan, the percentage of HPV positive OPC remained low around 17% -30% [ 8 – 12 ]. As a result, most clinicians pay more attention to HPV negative OPC without realizing the importance of HPV positive OPC in clinical practice nor in public health [ 1 , 13 – 15 ].…”

Human Papillomavirus and Squamous Cell Carcinoma of Unknown Primary in the Head and Neck Region: A Comprehensive Review on Clinical Implications

“…In the western world, OPSCCs are reported to be caused by HPV in the majority of patients, and there was an upsurge of HPV-induced OPSCC in the United States from 16% in the 1980s to more than 70% during the 2000s [ 22 ]. The high incidence of HPV-induced OPSCC is also seen in a number of European countries, with an increase from 35% before 2000 to 73% after 2005 [ 23 ], whereas HPV positivity in Asia is reported to occur in 20–34% of OPSCCs [ 24 , 25 , 26 , 27 ] with an increasing incidence [ 24 , 25 , 27 ].…”