Sinonasal Squamous Cell Carcinoma: Etiology, Pathogenesis, and the Role of Human Papilloma Virus

Abstract

Purpose of Review-Sinonasal squamous cell carcinoma (SNSCC) is a rare disease with considerable histologic diversity. Currently, there is a poor understanding of the etiology and pathogenesis of SNSCC. Here, we review recent literature to summarize what is known regarding (1) the etiology of SNSCC, (2) the role of Human Papilloma Virus (HPV) in SNSCC, and (2) the molecular underpinnings of SNSCC. Recent Findings-1. High risk HPVappears to play a role in the pathogenesis of a subset of SNSCCs. SNSCCs with high risk HPV have improved survival compared with those without HPV and occur in patients who are younger, similar to HPV mediated oropharyngeal cancer. 2. A subset of inverted papillomas have transcriptionally active low-risk HPV and have a higher risk of transformation, while low risk HPV negative inverted papillomas frequently have EGFR mutations. Summary-SNSCC is a diverse disease with likely multiple etiologies including carcinogen, irritant exposure, and HPV. While not definitively proven, evidence supports a role for high-risk HPV in a subset of SNSCC, and low-risk HPV in a subset of inverted papillomas which transform to SNSCC. In-depth molecular and genomic studies are needed in SNSCC to better understand the genomic underpinnings and oncogenic drivers.

Human Papillomavirus in Sinonasal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis

“…Despite this, findings of this analysis are in line with our pre-existing hypotheses, increasing confidence in our conclusions. Due to the high levels of heterogeneity between datasets and the large number of missing variables needed to accurately perform subgroup analyses, we chose not to evaluate certain factors which are likely to impact true HPV+ SNSCC prevalence rates such as association with papilloma, histologic subtypes and viral genotype [ 7 ]. Of note, recent reports have highlighted SNSCCs which arise from inverted papillomas and are associated with low risk HPV types 6/11 [ 106 ].…”

“…The first evidence for a potential etiological role of HPV in sinonasal squamous cell carcinoma (SNSCC) tumorigenesis arose in 1983 with the detection of HPV DNA by Syrjänen et al [ 6 ]. Since this time, mounting histologic and epidemiologic evidence suggests a subset of SNSCCs may be HPV-driven, and that similar to HPV+ OPSCC, HPV detection in SNSCC may be a biomarker for improved survival [ 7 , 8 , 9 , 10 , 11 ]. However, small sample sizes and variable HPV detection techniques, each with wide ranges in sensitivity and specificity, continue to hinder definitive conclusions.…”

Sinonasal analogue HPV related breast multiphenotypic carcinoma, a report of a case with the first description in the breast

“…The surface of the nipple and lactiferous duct showed markedly atypical squamous cells with dyskeratotic keratinocytes and squamous pearl formation, comparable to the previously described HSMC of the head and neck region. The immunohistochemical profile of this tumor consisting of p63 and high weight cytokeratin 5/6, 17 and 14 positivity in the tumor cells along with EGFR immunoreactivity are immunophenotypically compatible with HSMC and a "basal-like breast carcinoma" or "core basal" phenotype as defined by the Neilson Criteria [14]. Cases of HPVrelated multiphenotypic carcinoma of the breast resembling HMSC have not previously been reported in the literature.…”

“…Histologically, HMSC presents as either a high grade keratinized or non-keratinized squamous cell carcinoma with a salivary gland carcinoma component that demonstrates solid nests of basaloid cells with myoepithelial differentiation [9,11,12]. The association of high-risk HPV, particularly type 33 was thought to be exclusive of this tumor in the sinonasal tract in the head and neck area [1,13] [14]. While high risk HPV has been described in other tumors and associated with salivary type adenoid cystic carcinoma (ACC) of the uterine cervix, this entity is very rare [12].…”

Histopathology of Sinonasal and Nasopharyngeal Neoplastic Lesions in a Tertiary Care Center of Western Nepal: A Descriptive Cross-sectional Study

“…8 SN and NAP region comprise only 3-5% of all head and neck malignancies, and SCC is the most common subtype consisting more than 50% of cases. 23,24 Although the pathogenesis of SCC is poorly understood, carcinogen exposure due to occupational hazards, viral oncogenesis related to Human Papilloma Virus, INP as a precursor lesion, and a state of ongoing chronic inflammation are related towards the causation of SCC in the sinonasal and nasopharyngeal region. 24,25 Study of Begum MS, et.…”