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. 2016 Dec 27;7(52):86730-86739.
doi: 10.18632/oncotarget.13502.

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

Louise Soo Yee Tan  1 , Petersson Fredrik  2 , Liang Ker  1 , Feng Gang Yu  1 , De Yun Wang  3 , Boon Cher Goh  4 , Kwok Seng Loh  1   3 , Chwee Ming Lim  1   3
Affiliations

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

Louise Soo Yee Tan et al. Oncotarget. .

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.

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

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Conflict of interest statement

CONFLICTS OF INTEREST

None.

Figures

Figure 1
Figure 1. Representative plot of the nitrocellulose strip with HPV genotype-specific probes
Positive control, negative control, Oropharynx SCC, Laryngeal SCC, Hypopharynx SCC, Oral cavity SCC and human β-globin controls were shown.
Figure 2
Figure 2. Representative pictures of immunohistochemical staining of p16
(A) P16-negative (B) and p16-positive oropharyngeal squamous cell carcinoma (magnification ×200).
Figure 3
Figure 3. Kaplan-Meier curves showing (A) overall survival and; (B) disease-specific survival of p16-positive and p16-negative patients with oropharyngeal SCC
Black line = p16-positive, dashed line= p16-negative. The p16-positive OPSCC has a significantly better overall survival (p = 0.022), but not disease-specific survival (p = 0.46).
Figure 4
Figure 4. Overall survival of oropharyngeal SCC patients stratified according to smoking status
Black line = smoker, dashed line = non-smoker. Non-smokers have a significantly better overall survival (p = 0.007) compared to smokers.
Figure 5
Figure 5. Overall survival of oropharyngeal SCC patients stratified according to alcohol consumption status
Black line = drinker, dashed line = non-drinker. Non-drinker has a significantly better overall survival (p = 0.01) compared to drinker.
See this image and copyright information in PMC

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