Research Papers:

High-risk HPV genotypes and P16INK4a expression in a cohort of head and neck squamous cell carcinoma patients in Singapore

Louise Soo Yee Tan, Petersson Fredrik, Liang Ker, Feng Gang Yu, De Yun Wang, Boon Cher Goh, Kwok Seng Loh and Chwee Ming Lim _

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Oncotarget. 2016; 7:86730-86739. https://doi.org/10.18632/oncotarget.13502

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Louise Soo Yee Tan1, Petersson Fredrik2, Liang Ker1, Feng Gang Yu1, De Yun Wang3, Boon Cher Goh4, Kwok Seng Loh1,3, Chwee Ming Lim1,3

1Department of Otolaryngology-Head and Neck Surgery, National University Health System Singapore, Singapore 119228

2Department of Pathology, National University Health System Singapore, Singapore 119228

3Department of Otolaryngology, National University of Singapore, Singapore 119228

4Department of Medical Oncology, National University Health System Singapore, Singapore 119228

Correspondence to:

Chwee Ming Lim, email: [email protected]

Keywords: human papillomavirus, p16 immunohistochemistry, HPV DNA, head and neck squamous cell carcinoma, oropharyngeal squamous cell carcinoma

Received: June 29, 2016     Accepted: November 09, 2016     Published: November 22, 2016


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.

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