Abstract

Human papillomavirus (HPV), especially HPV16 genotype, is associated with oropharyngeal squamous cell carcinoma (OPSCC). We aim to determine the prevalence and characterize the high-risk (HR)-HPV genotypes in head and neck SCC (HNSCC) in a South-East Asian multi-ethnic society in Singapore and examine its prognostic significance.159 HNSCC archival tissue samples were retrieved and tumour DNA was screened for 18 HR-HPV genotypes using a PCR-based assay (Qiagen, digene HPV genotyping RH test). P16 protein overexpression was identified using immunohistochemistry (IHC). Statistical correlation between clinical outcomes were performed between HPV-positive and negative HNSCC patients.Six HR-HPVs (HPV16, 18, 31, 45, 56, 68) were detected in 90.6% of HNSCC; and 79.9% had multiple HPV genotypes detected. HPV31 and HPV45 were the most prevalent (79.2% and 87.4%, respectively); and HPV16 was predominantly found in OPSCC (p < 0.001). HPV-DNA PCR assay yielded a high sensitivity (96%) but low specificity (11%) when compared to p16 immunohistochemistry as the reference standard.P16-positive HNSCC was predominantly observed in OPSCC (73.7%; p = 0.005); and p16-positive OPSCC exhibited improved overall survival compared to p16-negative OPSCC (p = 0.022). Similarly, smoking and alcohol consumption were poor prognostic factors of overall survival (p = 0.007; p = 0.01) in OPSCC patients.HR-HPVs were identified in 90.6% of HNSCC patients using the HPV-DNA PCR assay. This test had a poor specificity when compared to p16 IHC; making it an unreliable detection technique in selecting patients for radiation dose de-escalation treatment protocol. P16-positive tumor was predominantly found in the oropharynx these patients demonstrated better overall survival than those with p16-negative OPSCC.

Highlights

  • There is firm evidence that human papillomavirus (HPV) is implicated in the pathogenesis of a subset of patients with head and neck squamous cell carcinoma (HNSCC) who are typically younger and without the traditional risk factors of smoking and alcohol consumption [1,2,3,4]

  • When we analyzed the specific HR-Human papillomavirus (HPV) genotypes according to sites of cancer, only HPV16 was predominantly detected in oropharyngeal squamous cell carcinoma (OPSCC) than non-OPSCC sites (p < 0.001)

  • We have chosen the digene HPV genotyping RH test kit because it detects a panel of HRHPV genotypes which is associated with cervical cancer [5, 6, 12]

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Summary

Introduction

There is firm evidence that human papillomavirus (HPV) is implicated in the pathogenesis of a subset of patients with head and neck squamous cell carcinoma (HNSCC) who are typically younger and without the traditional risk factors of smoking and alcohol consumption [1,2,3,4]. Most of these HPV-associated HNSCCs are found in the oropharyngeal subsite of tonsil and base of tongue [4]. This data is predominantly derived from Caucasian populations and the prevalence of HPV in HNSCC among Asian patients is not well characterized

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