title: High-risk HPV genotypes and P16INK4a expression in a cohort of head and neck squamous cell carcinoma patients in Singapore.
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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, National University Health System Singapore, Singapore 119228.
authors.forename: Louise Soo Yee
authors.initials: LS
authors.lastname: Tan
authors.affiliation: Department of Pathology, National University Health System Singapore, Singapore 119228.
authors.forename: Petersson
authors.initials: P
authors.lastname: Fredrik
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, National University Health System Singapore, Singapore 119228.
authors.forename: Liang
authors.initials: L
authors.lastname: Ker
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, National University Health System Singapore, Singapore 119228.
authors.forename: Feng Gang
authors.initials: FG
authors.lastname: Yu
authors.affiliation: Department of Otolaryngology, National University of Singapore, Singapore 119228.
authors.forename: De Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, National University Health System Singapore, Singapore 119228.
authors.forename: Boon Cher
authors.initials: BC
authors.lastname: Goh
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, National University Health System Singapore, Singapore 119228.|Department of Otolaryngology, National University of Singapore, Singapore 119228.
authors.forename: Kwok Seng
authors.initials: KS
authors.lastname: Loh
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, National University Health System Singapore, Singapore 119228.|Department of Otolaryngology, National University of Singapore, Singapore 119228.
authors.forename: Chwee Ming
authors.initials: CM
authors.lastname: Lim
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000208:ethnology / Q000378:metabolism* / Q000821:virology; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D005260:Female; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000208:ethnology / Q000378:metabolism* / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000208:ethnology / Q000235:genetics / Q000821:virology; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000208:ethnology / Q000378:metabolism* / Q000821:virology; D012846:Singapore; D055815:Young Adult
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16
keywords: HPV DNA; head and neck squamous cell carcinoma; human papillomavirus; oropharyngeal squamous cell carcinoma; p16 immunohistochemistry