Detection of serum biomarkers of HPV-16 driven oropharynx and oral cavity cancer in Brazil

• Published in: Oral oncology 2024-02, Vol.149, p.106676-106676, Article 106676
• Main Authors: Sichero, Laura, Gonçalves, Milena Giulia, Bettoni, Fabiana, Coser, Elisangela Monteiro, Mota, Giana, Nunes, Rafaella A L, Mercante, Ana Maria da Cunha, Natalino, Renato, Uno, Miyuki, Ferreira Alves, Maria José, Matos, Leandro Luongo, Kowalski, Luiz Paulo, Kulcsar, Marco Aurélio Vamondes, de Alvarenga, Gustavo Fernandes, Höfler, Daniela, Schroeder, Lea, Waterboer, Tim, Tommasino, Massimo, Villa, Luisa Lina
• Format: Article
• Language: English
• Subjects: Biomarkers; Brazil - epidemiology; Cyclin-Dependent Kinase Inhibitor p16 - genetics; DNA, Viral - analysis; Head and Neck Neoplasms - complications; Human papillomavirus 16 - genetics; Humans; Mouth Neoplasms - complications; Oropharyngeal Neoplasms; Papillomavirus Infections; RNA
• ISSN: 1368-8375; 1879-0593
• DOI: 10.1016/j.oraloncology.2023.106676

HPV-16 driven oropharynx/oral cavity squamous cell carcinomas prevalence varies globally. We evaluated the presence of HPV-16 ctDNA and HPV-16 E6 antibodies in samples obtained from participants treated at the Instituto do Cancer do Estado de Sao Paulo, ICESP, and from whom tumoral HPV DNA, HPV-16 E6*I mRNA, and p16 status was also accessed. HPV was genotyped by PCR-hybridization. All HPV DNA positive and ∼10 % HPV DNA negative cases underwent p16 immunohistochemistry and E6*I RNA testing using a multiplex bead based protocol. HPV-16 ctDNA and anti-E6 antibodies were assessed by ddPCR (digital droplet PCR) and multiplex serology, respectively. The prevalence of HPV-16 in oropharynx carcinoma (OPC) cases was low (8.7 %) when considering solely HPV-16 DNA detection, and even lower (5.2 %) when taken into consideration the concomitant detection of HPV-16 E6*I RNA and/or p16 (HPV-16 attributable fraction - AF). None of the oral cavity cancer (OCC) cases were detected with HPV-16 DNA. HPV-16 ctDNA was more commonly detected than HPV-16 E6 antibodies (29.8 % versus 10.6 %). Both serum biomarkers attained 100 % sensitivity of detecting HPV-16 AF OPC, however the specificity of the HPV-16 anti-E6 biomarker was higher compared to ctDNA (93.2 % versus 75.0 %). Finally, when both HPV-16 ctDNA and anti-E6 biomarkers were considered together, the sensitivity and specificity for HPV-16 OPC detection was 100 % and about 70 %, respectively, independently of analyzing HPV-16 DNA positive or HPV-16 AF tumors. Our findings corroborate that serum biomarkers are highly sensitive and specific biomarkers for detection of HPV-associated OPC.