Transcriptionally Active Human Papillomavirus Infection in a Minority of Esophageal Squamous Cell Carcinomas in North America

• Published in: The American journal of surgical pathology Vol. 48; no. 7; pp. 883 - 889
• Main Authors: Bauer, Anna H, Alkhateeb, Khaled J, Agoston, Agoston T, Odze, Robert D, Joshi, Megha G, Huffman, Brandon M, Enzinger, Peter, Perez, Kimberly, Deshpande, Vikram, Cleary, James M, Wee, Jon O, Dong, Fei, Zhao, Lei
• Format: Journal Article
• Language: English
• Published: United States 01-07-2024
• Subjects: Aged; Biomarkers, Tumor - genetics; Chemoradiotherapy, Adjuvant; DNA, Viral - genetics; Esophageal Neoplasms - genetics; Esophageal Neoplasms - pathology; Esophageal Neoplasms - therapy; Esophageal Neoplasms - virology; Esophageal Squamous Cell Carcinoma - genetics; Esophageal Squamous Cell Carcinoma - pathology; Esophageal Squamous Cell Carcinoma - therapy; Esophageal Squamous Cell Carcinoma - virology; Female; High-Throughput Nucleotide Sequencing; Human papillomavirus 16 - genetics; Human papillomavirus 16 - isolation & purification; Human Papillomavirus DNA Tests; Humans; Male; Middle Aged; Mutation; Neoadjuvant Therapy; North America - epidemiology; Papillomavirus Infections - complications; Papillomavirus Infections - therapy; Papillomavirus Infections - virology; Transcription, Genetic; Treatment Outcome; Tumor Suppressor Protein p53 - genetics; North America
• ISSN: 0147-5185; 1532-0979; 1532-0979
• DOI: 10.1097/PAS.0000000000002235

The role of Human papillomavirus (HPV) infection in esophageal squamous cell carcinoma (ESCC) is a topic of ongoing debate. This study used two screening approaches to look for evidence of HPV infection in esophageal squamous cell carcinoma. We initially checked for HPV infection in a randomly selected group of 53 ESCC cases. We did not detect any tumors positive for high-risk HPV. However, during clinical practice, we identified an HPV-positive ESCC in the distal esophagus, which tested positive for HPV16. This index case was TP53 wild-type, as determined by next-generation DNA sequencing (NGS). Since TP53 mutations are rare in other HPV-driven cancers, we improved our screening method by limiting our screen to a subset of ESCC cases without TP53 mutations. A second screen of 95 ESCCs (from 93 patients) sequenced by NGS revealed an additional 7 ESCCs with TP53 wild-type status (7.3% of the total). Of the 7 cases, 2 cases were found to be high-risk HPV positive. Both patients also tested positive for circulating cell-free HPV DNA and had a complete response to neoadjuvant chemoradiation. The index patient had microscopic residual tumor following neoadjuvant therapy. The patient underwent adjuvant immunotherapy and remained disease free after 22 months of surveillance. This study affirms the transcriptionally active status of high-risk HPV in a minority of ESCC patients in North America.