Date of Award

January 2025

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Saral Mehra

Abstract

Objective: To fully characterize the disease course of recurrent HPV+ oropharyngealsquamous cell carcinoma (OPSCC) treated within our five-hospital health system. More specifically, our two aims are to detail patterns of recurrence in HPV+ oropharyngeal cancer through a systematic literature review and an analysis of our own institutional cohort and to characterize the impact of tobacco use — a driver of HPV- disease — on HPV+ recurrence-free and overall survival. Methods: We conducted a systematic review through MEDLINE to identify articles that discussed patterns of recurrent HPV+ OPSCC. Initial data on all patients diagnosed with HPV+ OPSCC was acquired through the institutional tumor registry and additional variables were obtained through retrospective chart review to create a 367-person cohort of patients diagnosed with and treated for HPV+ OPSCC at our 5-hosptial health system. An additional 37-person cohort of patients with “true” recurrent HPV+ OPSCC was identified, with their initial disease-free state established by post-treatment imaging. We then looked at recurrence location and identified how each recurrence was detected. After that, we conducted survival analyses and examined time to recurrence stratified by these metrics. We additionally used the full 367-patient cohort to conduct a systematic analysis of the impact of four smoking metrics on 3-year recurrence-free (RFS) and overall survival (OS). Results: From 9 full-text articles that met the inclusion criteria for the systematic review, the average recurrence rate across all studies was 12.7%. HPV+ OPSCC recurrence can occur several years after primary treatment completion, and in multiple distant locations. Of the 37 patients that met the criteria for experiencing true recurrent disease, 56.7% (21/37) of patients experienced locoregional disease recurrence and 43.2% (16/37) of patients experienced distant metastasis. The most common sites of distant metastasis were to the lung, the brain/central nervous system, the liver, and bone. Mean time to recurrence for locoregional disease was 2.46 ± 1.94 years compared to 1.89 ± 0.87 years for distant metastasis. For the smoking analyses conducted using the full patient cohort, all four tobacco-use metrics assessed did not impact 3-year RFS, but smoking did have a negative impact on 3-year OS. Conclusion: While HPV+ OPSCC remains a more favorable disease entity than its HPV- counterpart, there are potentially important differences in driving factors as well as in recurrence patterns. There is a dearth of literature characterizing how recurrent HPV+ disease is identified, but it appears consistent between our systematic review and institutional data that recurrent HPV+ OPSCC can metastasize to multiple distant sites, and mean/median time to recurrence for this disease type is over one year. Future work should be done to understand whether surveillance imaging after primary treatment completion would have positive impacts on salvage treatment morbidity. Finally, HPV+ OPSCC recurrence was not negatively impacted by smoking in this institutional disease cohort.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 05/14/2027

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