Main Session
Sep
29
PQA 07 - Head and Neck Cancer, Lung Cancer/Thoracic Malignancies, and Nursing and Supportive Care
3508 - p16 and HPV Testing Discordance and Outcomes in a Large U.S. Cohort of Patients with Oropharyngeal Squamous Cell Carcinoma
Presenter(s)
Jacob Jordan, MD, MS - Mayo Clinic Rochester, Rochester, MN
J. A. Jordan1, A. Ness2, A. W. Bogan3, A. V. Chintakuntlawar4, R. Agwaze5, S. H. Patel6, A. L. Holtzman2, R. J. Brisson1, D. K. Ebner1, S. C. Lester1, T. D. Malouff1, M. Neben Wittich1, D. J. Ma1, J. M. Wilson1, K. Price4, D. L. Price5, L. X. Yin5, J. S. Lewis7, K. Van Abel5, and D. M. Routman1; 1Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 2Mayo Clinic, Rochester, MN, 3Department of Qualitative Health Sciences, Section of Biostatistics, Mayo Clinic, Scottsdale, AZ, 4Division of Medical Oncology, Mayo Clinic, Rochester, MN, 5Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, MN, 6Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, 7Department of Pathology, Mayo Clinic, Phoenix, AZ
Purpose/Objective(s):
Oropharyngeal squamous cell carcinoma (OPSCC) represents a spectrum of disease primarily driven by HPV or tobacco. p16 overexpression is a common surrogate marker for HPV positivity. However, p16 and HPV testing can have discordant results, with each containing independent prognostic information. A recent Head and Neck Cancer International Group (HNCIG) paper demonstrated discordant populations have worse outcomes than concordant positive patients, and that both HPV incidence and concordance rate vary by country. Here, we analyzed a large cohort of patients in the United States.Materials/Methods:
We queried an institutional database of 2,755 patients with OPSCC treated with surgery, radiation, and/or chemotherapy from 1990 to 2025 across three sites of an academic center. We identified patients with both p16 and HPV testing by DNA or RNA. RNA testing was recently adopted as a clinical standard starting in 2017. Our goal was to report p16 and HPV discordance by testing type and analyze outcomes based on p16 and HPV status. We provide descriptive statistics and progression free survival (PFS) measurements across testing groups with log-rank testing for differences.Results:
Overall, 2,755 patients were identified; 2,136 were p16+, 189 were p16–, and 430 were p16 unknown. 1,216 patients had p16 and DNA testing and 371 patients had p16 and RNA testing, and thus were included in the primary analysis. Patient characteristics were as follows: 86% male, 43% former smokers, 12% current smokers, and 75% T1 to T2. 82% of patients underwent primary surgical resection while 18% underwent chemoradiation. Discordance varied significantly by testing type, with 9.9% p16/DNA discordance rate as compared to p16/RNA discordance of 1.9% (no p-value comparison performed given non-mutually exclusive cohorts). Concordant positive cases (p16+/HPV+) had 2 yr and 5 yr PFS of 87% and 78%; concordant negative cases (p16–/HPV–) had 2 yr and 5 yr PFS of 57 % and 45%, while discordant cases (either p16+/HPV– or p16–/HPV+; HPV status determined by either DNA or RNA) had 2 yr and 5 yr PFS of 80% and 71%, respectively. PFS was significantly different between the concordant negative group and both the concordant positive and discordant groups (p<0.01); no significance found between the latter two groups.Conclusion:
HPV RNA testing led to lower p16/HPV discordant rates (1.9%) when compared to DNA tests (10%). This discordance is consistent with the HNCIG data. Discordant patients had better PFS than concordant negative patients. PFS was not statistically worse in our sample between concordant positive and discordant groups, though discordant patient trended towards worse PFS (which would match other cohorts). As p16/RNA discordance is lower than p16/DNA discordance, it remains to be seen if a detriment to PFS in discordant patients will remain with RNA as the HPV confirmatory test. This can be explored further as RNA-based cohorts mature. These findings should inform OPSCC testing, staging, and management in the US.