Frequency and Localization of Second Primary Tumors in Patients with Oropharyngeal Carcinoma—The Influence of the Human Papilloma Virus

SIMPLE SUMMARY: Human papillomavirus (HPV) infection, smoking, and excessive alcohol consumption have been established as risk factors for the development of oropharyngeal squamous cell carcinoma (OPSCC). While the HPV epidemic has led to an increasing incidence of OPSCC, HPV-negative OPSCC cases associated with smoking and alcohol remain stable. As HPV-positive and -negative OPSCC present two distinct etiological, clinical, and prognostic entities, different treatment and follow-up strategies are being discussed. Still, specific surveillance strategies for HPV-positive OPSCC are lacking, as the risk of second primary tumors (SPT) in the era of HPV-associated OPSCC has not been comprehensively assessed. Our study investigated the frequency and localization of SPT of HPV-positive OPSCC, as well as their prognostic impact. We find that the SPT of HPV-positive OPSCC are less frequent than those of HPV-negative OPSCC, and they are also associated with higher survival rates. The localization of SPT of HPV-positive OPSCC did not differ from the localization of SPT of HPV-negative OPSCC. ABSTRACT: Purpose: To investigate the frequency, localization, and survival of second primary tumors (SPT) of oropharyngeal squamous cell carcinoma (OPSCC) depending on human papillomavirus (HPV) status. Methods: We performed a retrospective chart analysis of 107 OPSCC patients treated at the Zurich University Hospital from 2001 to 2010. Rate and localization of SPT after an index OPSCC were stratified according to smoking and HPV infection status. Results: In total, 57/91 (63%) included patients showed an HPV-associated OPSCC. Of these, 37/57 (64.9%) patients with an HPV-positive and 32/34 (94.1%) patients with an HPV-negative OPSCC were smokers. The median age at diagnosis of the SPT was 59.54 years (interquartile range 52.7–65.6). In addition, 8/57 (14%) HPV-positive and 13/34 (38.2%) HPV-negative patients developed SPT. The rate of SPT in patients with HPV-positive index tumors was significantly lower than in patients with HPV-negative OPSCC (p-value 0.01). Smokers showed significantly more SPT in the head and neck area than outside. The development of an SPT led to a significantly lower survival time in HPV-negative patients, while it did not significantly affect the survival time of HPV-positive patients. Conclusions: Patients with HPV-positive index tumors had a significantly lower risk of developing SPT than patients with HPV-negative tumors. If SPT developed, survival was significantly shorter in patients with HPV-negative tumors than with HPV-positive tumors.