Abstract LB137: Comparison of HPV virus-induced oropharyngeal cancer by self-reported race and the potential implications on treatment
Authors: Mabvakure Batsirai M. , Li Shiting , Herrera Deborah de la Caridad Delgado , Benjamin William , Cruz Lucia Martinez , Patil Siddhi , Mohebbi Elham , Wolf Gregory T. , Duttargi Anju , Lefante Christina , Hsieh Mei-Chin , D'Silva Nisha J. , Sartor Maureen , Rozek Laura 
Published: April 2024

Abstract
African Americans exhibit lower survival rates from Human Papillomavirus (HPV)-induced squamous cell carcinomas in comparison to other population groups. While socioeconomic status and access to healthcare may contribute to these disparities, mounting evidence indicates that significant biological differences between diverse ancestries play a role in the severity of different cancers such as breast cancer, colorectal cancer, and squamous cell carcinomas. The purpose of the study is to investigate diagnostic and biological differences in HPV-induced squamous cell carcinomas of the oropharynx by self-reported race.
The study population consists of oropharynx cases identified at the University of Michigan (non-Hispanic White) and through the Louisiana Tumor Registry (African American). A total of 52 individuals from two study sites were included in this study, 40 of whom are men, two are women and 10 are unknown. Forty-four percent (23/52) of individuals were African Americans (AA), and 46 % (19/52) were Non-Hispanic White (NHW).
Formalin-fixed paraffin-embedded (FFPE) tumors from these patients were tested for p16 expression via immunohistochemistry as a proxy for HPV status. Fifty-two percent (27/52) tested negative (p16-) and 48% (25/52) tested positive (p16+). Total RNA from these samples was extracted, sequenced, and bioinformatically analyzed to test for the presence of HPV. Among AA samples, 61% were negative for both p16 and HPV RNA (p16-/RNA-), 26% were p16+/RNA-, 13% were p16+/RNA+ and none were p16-/RNA+. Among NHWs, 37% were p16-/RNA-, 16% were p16-/RNA+, 47% were p16+/RNA+ and none were p16+/RNA-. Interestingly, 6 of 20 HPV RNA- AA samples were p16+, whereas 0 of 7 HPV RNA- NHW samples were p16+.
We performed data dimensionality reduction using Principal Component Analysis (PCA) implemented in the PCAtools Bioconductor package. Four groups were separated in a plot of the first two PCs, comprising, (i) all p16+/RNA+ (18/18), (ii) dominantly p16-/RNA- (6/7), (iii) p16-/RNA- mixed with p16+/RNA-, and (iv) p16-/RNA+ in the middle of all the groups and mixing with some p16+/RNA+ samples. A total of 13/17 (76%) p16-/RNA- samples in group (iii) that were mixed with p16+/RNA- samples were AA, 3 (18%) were NHW and 1 was unknown. Based on clinical data, the PCA group (iii) consisted of samples that were characterized as invasive, keratinizing, and moderately differentiated, whereas group (ii) samples were mostly clinically characterized as nonkeratinizing. A total of 13/14 AA samples that tested p16-/RNA- possessed similar clinical attributes as samples classified as p16+/RNA-, suggesting that the p16 expression via immunohistochemistry test might be classifying a significant percent of HPV-negative AA samples as positive.
Taken together, these results suggest that the p16 immunohistochemistry test for oropharyngeal cancer may be overly sensitive for classifying AA oropharynx cancer samples. Clinical decisions regarding treatment for AA based on this test have the potential to negatively impact outcomes.
Citation Format: Batsirai M. Mabvakure, Shiting Li, Deborah de la Caridad Delgado Herrera, William Benjamin, Lucia Martinez Cruz, Siddhi Patil, Elham Mohebbi, Gregory T. Wolf, Anju Duttargi, Christina Lefante, Mei-Chin Hsieh, Nisha J. D'Silva, Maureen Sartor, Laura Rozek. Comparison of HPV virus-induced oropharyngeal cancer by self-reported race and the potential implications on treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB137.