Negative human papillomavirus status and excessive alcohol consumption are significant risk factors for second primary malignancies in japanese patients with oropharyngeal carcinoma

Objective: To determine the clinical significance of human papillomavirus subclinical infection in patients with oropharyngeal squamous cell carcinoma in Japan. Methods: Over a 9-year period, a retrospective case comparison study of the pathology database was conducted at the University of Tokyo to identify samples of oropharyngeal squamous cell carcinoma.We performed in situ hybridization for human papillomavirus-DNA to identify subclinical human papillomavirus infections among patients with oropharyngeal squamous cell carcinoma. Second primary malignancies were classified as synchronous, if identified within 6 months of the diagnosis of the first tumor, or metachronous, if identified after this 6-month period. Univariate and multivariate analyses using logistic stepwise regression models were performed to identify factors associated with synchronous and metachronous second primary malignancy. Results: Of the 150 patients with oropharyngeal squamous cell carcinoma, 14% (21/150) and 20.7% (31/150) developed synchronous and metachronous second primary malignancies, respectively. Esophageal carcinoma was the most frequent second primary malignancy (10/21 for synchronous and 10/31 for metachronous second primary malignancies). The prevalence of oropharyngeal squamous cell carcinoma positive for human papillomavirus was 31% (47/150). Multivariate analysis identified alcohol consumption as a significant unfavorable risk factor for the occurrence of synchronous second primary malignancy, and either a human papillomavirusnegative status or N0 classification was a significant unfavorable risk factor for the occurrence of metachronous second primary malignancy. Conclusions: Evaluation of the human papillomavirus status may help identify patients at risk for metachronous second primary malignancy. Upper gastrointestinal endoscopy is very important in the diagnosis of oropharyngeal squamous cell carcinoma among heavy drinkers in Japan.