Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Importance: Second primary tumors may occur due to field cancerization both in Human Papillomavirus (HPV) negative head and neck cancer (HPV- HNC) and HPV positive head and neck cancer (HPV+ HNC). We have previously reported on the higher-than-expected rate of HPV+/HPV+ second primaries. Second primary tumors have been assumed, and reported, to be the same tumor type both for HPV+, with recent changes to pathology guidelines suggesting limited utility in repeat HPV testing for recurrent tumors. However, here we report a novel phenomenon of second primary HPV-HNC following HPV+HNC.
Objectives: To report a novel case series of second primary head and neck cancers with discordant HPV status.
Methods: This study involves a case series of patients at the Massachusetts Eye and Ear who underwent treatment for HPV-positive HNC and subsequently developed an HPV-negative HNC at a different subsite. Basic demographic and pathologic data were recorded. Modality of HPV testing was collected. Any patient for which only p16 data was present was re-reviewed pathologically using either HPV-PCR or ISH to confirm HPV status.
Results: We identified 12 patients with HPV-positive OPSCC who developed an HPV-negative second HNC between 2020 to 2024 at our institution, confirmed through both direct HPV testing (PCR/ISH) and p16 staining. HPV-negative second primaries were identified on average 10 years (0.6-12.4 years) after treatment of the first HPV-positive primary. Eleven patients (92%) underwent definitive chemoradiotherapy (CRT) treatment for their first HPV+ OPSCC. 7 patients (54%) reported no smoking history, and 11 patients (92%) were men, all of whom were white. The median age of the cohort was 60 years (35-77). The initial subsites of HPV+ HNC subsites included: 6 patients (50%) with tonsil tumors, 5 patients (42%) with base of tongue tumors, and 1 with unknown primary tumor with a negative pan-endoscopy with biopsies. The subsites of second primary HPV- HNC identified were: 7 contralateral base of tongue (58%), 3 oral cavity (25%), 1 posterior pharynx (8%), and 1 epiglottis (8%). All of the second tumors were treated with upfront surgery, with 3 patients receiving adjuvant radiotherapy. Three patients developed HPV-HNC recurrences after the second primary tumor, one of which died one month after recurrence from airway invasion, and the other two who remain on chemoimmunotherapy for management.
Conclusion: Here we reported a novel phenomenon of secondary primary cancers with discordant HPV status. Interestingly, in all cases, the HPV positive tumor preceded the HPV negative tumor. Further research into the biological mechanisms driving this phenomenon is needed.