Is p16 immunohistochemistry sufficient to define HPV-related oropharyngeal carcinomas?

Introduction The characterization of human papillomavirus (HPV) infection in oropharyngeal carcinomas is prognostically relevant, but there may be discordance between p16 expression and molecular detection of viral DNA.Materials and methods Retrospective study of 620 patients with squamous cell carcinoma of the oropharynx treated between 1991 and 2024 with joint determination of HPV by PCR and p16. Epidemiological, clinical, and therapeutic characteristics were analyzed according to HPV status, as well as specific, overall, and recurrence-free survival.Results Overall, 74.0% of tumors were PCR-/p16-, 19.4% were PCR+/p16+, and 6.6% were discordant (3.9% PCR+/p16-; 2.7% PCR-/p16+). Five-year specific survival was significantly higher in the PCR+/p16+ group (P = 0.0001). No differences in survival were observed between the discordant and double-negative groups (P = 0.311). In the multivariable analysis, considering PCR+/p16+ patients as the reference category, the risk of death from tumor was 4.97 times higher in PCR+/p16-, 5.42 times higher in PCR-/p16+, and 3.63 times higher in PCR-/p16-. Similar findings were obtained in the cohort treated with radical intent. The prognostic differences remained for deaths from oropharyngeal tumor, second neoplasm, or non-oncological causes.Conclusions Only double-positive tumors (PCR+/p16+) show the prognostic benefit of HPV-related oropharyngeal carcinomas. Discordant tumors had a similar outcome to double-negative tumors. The combination of PCR and p16 improves prognostic accuracy and allows for the adequate identification of patients who are candidates for specific therapeutic strategies.