Lack of De‐Intensification Models for Female Head and Neck Cancer Patients With Favorable Prognosis

PURPOSE: The prognostic relevance of gender in head and neck cancer is often neglected. In contrast, the more favorable prognosis of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is well recognized, and de-escalation strategies are increasingly being tested in clinical trials. In this study, we focused on the prognostic significance of gender to clarify whether it should be given more attention. PATIENTS AND METHODS: We requested data on patients with newly diagnosed head and neck cancer between 2002 and 2017 from the German Center of Cancer Registry (n = 212,920). First, we focused on sex-specific survival according to primary tumor site in a nationwide context. Second, we examined a local dataset of 462 OPSCC patients, diagnosed at the University Hospitals of Ulm and Lübeck between 2005 and 2018 and followed up until 2024. Here we compared the prognostic value of sex with HPV status, alcohol consumption, and smoking habits (these parameters were not available at national level). RESULTS: In the nationwide analysis, women showed better survival in all head and neck primary tumor sites studied. The mean survival difference was greatest in patients with OPSCC (1.3 years; p < 0.0001), followed by patients with nasopharyngeal carcinoma (1 year; p < 0.0001). In the subgroup of patients younger than the median age (62.8 years), women lived on mean 1.2 times longer than men (p < 0.0001). Besides, in the local dataset, men with HPV-positive OPSCC did not have a better prognosis than women, even when HPV-negative (p = 0.426). However, the prognostic effect of female sex may be attenuated in patients with high tobacco use; in this scenario, no sex-related difference in survival was found (p = 0.56). CONCLUSION: Sex-specific differences in survival, especially in OPSCC and nasopharyngeal cancers, suggest the implementation of gender-sensitive oncology regarding prevention, treatment, and aftercare.