HPV-positive Squamous Cell Carcinoma of the Larynx, Oral Cavity, and Hypopharynx

Abstract

Human papillomavirus (HPV) is a principal driver for most oropharyngeal squamous cell carcinomas (OPSCCs), where it is strongly associated with improved survival. HPV is much less frequently detected in squamous cell carcinomas arising in nonoropharyngeal sites (non-OPSCCs), and its pathogenic role and prognostic value in these tumors is unclear. We evaluated the clinicopathologic features of 52 non-OPSCCs considered HPV-positive based upon p16 immunohistochemistry and direct HPV detection using RNA in situ hybridization (ISH), DNA ISH, or real-time DNA polymerase chain reaction. The HPV-positive non-OPSCCs were from the larynx (n=27), oral cavity (n=21), and hypopharynx (n=4). While most cases (n=34, 65%) showed classic histologic features of HPV-positive OPSCC, including endophytic growth, minimal keratinization, and hyperchromatic nuclei without koilocytic changes, a subset (n=13, 25%) were characterized by exophytic growth, exuberant surface hyperkeratosis and parakeratosis, marked nuclear pleomorphism, and prominent koilocytic atypia. These antithetical features were highly reminiscent of the warty variant of HPV-positive squamous cell carcinoma described in anogenital sites. Compared with tumors without warty features, the warty tumors presented at lower stage and were not associated with lymph node metastasis, local recurrence, or distant spread (4 y disease-free survival of 100% vs. 66%, P=0.069). The presence of transcriptionally active HPV as detected by RNA ISH suggests a pathogenic role for HPV in these nonoropharyngeal sites. While most HPV-positive non-OPSCCs are morphologically similar to their tonsillar counterparts, this study highlights a previously unrecognized warty variant that may be associated with a highly favorable clinical outcome.

The Role of the Oral Microbiota in the Etiopathogenesis of Oral Squamous Cell Carcinoma

“…Viruses constituting a part of oral microbiota can be detected both in their active and latent form; they are associated with many diseases of the oral cavity [ 90 ]. Over the last years, the role of viruses in the development of oral carcinoma has been the focus of many studies [ 92 , 93 , 94 , 95 ].…”

Cuproptosis-Related lncRNAs are Biomarkers of Prognosis and Immune Microenvironment in Head and Neck Squamous Cell Carcinoma

“…HNSC is a complex disease. Typical risk factors are smoking, excessive alcohol consumption, and human papillomavirus (Jamal et al, 2016;Rooper et al, 2020). Although the current treatment methods for HNSC include surgery and chemoradiotherapy, the recurrence rate and metastasis risk of HNSC are still very high (Camisasca et al, 2011).…”

Presence of Human Papillomavirus and Epstein–Barr Virus, but Absence of Merkel Cell Polyomavirus, in Head and Neck Cancer of Non-Smokers and Non-Drinkers

“…NSD1 is coding for Histone H3K36 methyltransferase, which is associated with DNA hypomethylation, resulting in p16 overexpression when mutated by not being able to regulate its expression via methylation anymore (36). Indeed, p16 overexpression has been reported in non-OPSCC, without a correlation to HPV infection nor as a predictor for survival (34,38). Therefore, The College of American Pathologists does not endorse routine p16 screening for non-OPSCC (39).…”