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.
Subject(s)
Alphapapillomavirus/isolation & purification , Papillomavirus Infections/epidemiology , Squamous Cell Carcinoma of Head and Neck/epidemiology , Viral Proteins/genetics , Adult , Alphapapillomavirus/genetics , Alphapapillomavirus/pathogenicity , Disease-Free Survival , Female , Human papillomavirus 16/isolation & purification , Human papillomavirus 16/pathogenicity , Humans , Male , Middle Aged , Neoplasm Staging , Papillomavirus Infections/complications , Papillomavirus Infections/genetics , Papillomavirus Infections/virology , Prognosis , Squamous Cell Carcinoma of Head and Neck/complications , Squamous Cell Carcinoma of Head and Neck/genetics , Squamous Cell Carcinoma of Head and Neck/virology , Nicotiana/adverse effectsABSTRACT
The invasion of bladder cancer into the sub-urothelial muscle and vasculature are key determinants leading to lethal metastatic progression. However, the molecular basis is poorly understood, partly because of the lack of uncomplicated and reliable models that recapitulate the biology of locally invasive disease. We developed a surgical grafting technique, characterized by a simple, rapid, reproducible and high-efficiency approach, to recapitulate the pathobiological events of human bladder cancer invasion in mice. This technique consists of a small laparotomy and direct implantation of human cancer cells into the bladder lumen. Unlike other protocols, it does not require debriding of the urothelial lining, injection into the bladder wall, specialized imaging equipment, bladder catheterization or costly surgical equipment. With minimal practice, the procedure can be executed in <10 min. Tumors develop with a high take rate, and most cell lines exhibit local invasion within 4 weeks of implantation.