Long-Term Survival and Recurrence in Oropharyngeal Squamous Cell Carcinoma in Relation to Subsites, HPV, and p16-Status

SIMPLE SUMMARY: Long-term survival in patients with oropharyngeal cancer is sparsely studied, but atypical recurrences in human papillomavirus-positive (HPV+) oropharyngeal cancer have been indicated. Furthermore, while the role of HPV is well established in tonsillar and base of tongue cancer, the dominant oropharyngeal subsites, its role in the minor oropharyngeal sites (the oropharyngeal walls, the uvula, and the soft palate) is not fully elucidated. The aim of this retrospective study was therefore to assess long-term outcome in relation to oropharyngeal sub-sites and HPV/p16 status. We confirm the prognostic role of p16+ in tonsillar and base of tongue cancer, but not the other sites. We find that combined HPV/p16-status gives better prognostic information than p16 alone. Lastly, we show that p16− cancer has more locoregional and late recurrences compared to p16+ cancer. Consequently, only combined HPV/p16 positivity in patients with tonsillar and tongue base cancer should be used in future treatment de-escalation trials. ABSTRACT: Long-term survival data in relation to sub-sites, human papillomavirus (HPV), and p16(INK4a) (p16) for patients with oropharyngeal squamous cell carcinoma (OPSCC) is still sparse. Furthermore, reports have indicated atypical and late recurrences for patients with HPV and p16 positive OPSCC. Therefore, we assessed long-term survival and recurrence in relation to oropharyngeal subsite and HPV/p16 status. A total of 529 patients with OPSCC, diagnosed in the period 2000–2010, with known HPVDNA and p16-status, were included. HPV/p16 status and sub-sites were correlated to disease-free and overall survival (DFS and OS respectively). The overexpression of p16 (p16(+)) is associated with significantly better long-term OS and DFS in tonsillar and base of tongue carcinomas (TSCC/BOTSCC), but not in patients with other OPSCC. Patients with HPVDNA(+)/p16(+) TSCC/BOTSCC presented better OS and DFS compared to those with HPVDNA(−)/p16(−) tumors, while those with HPVDNA(−)/p16(+) cancer had an intermediate survival. Late recurrences were rare, and significantly more frequent in patients with p16(−) tumors, while the prognosis after relapse was poor independent of HPVDNA(+/−)/p16(+/−) status. In conclusion, patients with p16(+) OPSCC do not have more late recurrences than p16(−), and a clear prognostic value of p16(+) was only observed in TSCC/BOTSCC. Finally, the combination of HPVDNA and p16 provided superior prognostic information compared to p16 alone in TSCC/BOTSCC.