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

Tan, Louise; Petersson, Fredrik; Ker, Liang; Yu, Feng; Wang, De Yun; Goh, Boon Cher; Loh, Kwok Seng; Lim, Chwee Ming

doi:10.18632/oncotarget.13502

Cited by 14 publications

(15 citation statements)

References 37 publications

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“…However, there were considerable differences in the rates between regions and countries; the region with the highest prevalence was Oceania (49.32%) and the country with the lowest prevalence was China (9.50%) [ 30 ]. Our findings taken for cases diagnosed between 2009 and 2015 (35%) are comparable to the reported rates in East and South Asian regions (25.8 and 38.7% respectively) and Singapore (42%) [ 31 ]. In the present study, 80% of the p16 positive cases were from patients of Chinese ethnicity, whilst all the Indian patients had p16 negative OPSCC.…”

Section: Discussionsupporting

confidence: 88%

Clinico-pathological features of oropharyngeal squamous cell carcinomas in Malaysia with reference to HPV infection

Yap

Lai

Rhodes

et al. 2018

Infect Agents Cancer

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BackgroundThe incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been rising in Western countries and this has been attributed to human papillomavirus (HPV) infection. p16 expression is a marker for HPV infection and p16 positive OPSCC is now recognized as a separate disease entity. There are only limited data available regarding HPV-related OPSCC in Asian countries and no data from Malaysia.MethodsWe identified 60 Malaysian patients with OPSCC over a 12-year period (2004–2015) from four different hospitals in two major cities, Kuala Lumpur and Penang. The detection of HPV was carried out using p16 immunohistochemistry and high risk HPV DNA in situ hybridisation.ResultsOverall, 15 (25%) tumours were p16 positive by immunohistochemistry, 10 of which were also positive for high risk HPV DNA by in situ hybridisation. By comparison, a matched cohort of UK patients had a p16 positive rate of 49%. However, between 2009 and 2015, where cases were available from all four hospitals, 13 of 37 (35%) cases were p16 positive. In our Malaysian cohort, 53% of patients were of Chinese ethnicity and 80% of the p16 positive cases were found in these patients; no Indian patients had p16 positive disease, despite representing 35% of the total cohort.ConclusionThe proportion of OPSCCs associated with HPV in Malaysia appears to be lower than in European and American cohorts and could possibly be more prevalent amongst Malaysians of Chinese ethnicity. Further, our data suggests that the burden of HPV-related OPSCC could be increasing in Malaysia. Larger cross-sectional studies of Malaysian patients are required to determine the public health implications of these preliminary findings.

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Section: Discussionsupporting

confidence: 88%

Clinico-pathological features of oropharyngeal squamous cell carcinomas in Malaysia with reference to HPV infection

Yap

Lai

Rhodes

et al. 2018

Infect Agents Cancer

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“…However, indications increase that HPV-association is a positive predictive factor for SCCVs (Lee et al 2016;Horne et al 2018). Regarding oropharyngeal squamous cell cancer, several studies could verify p16 as a reliable surrogate marker for HPV-association (Prigge et al 2017;Ma and Lewis 2012;Tan et al 2016). However, it seems to be of interest that overexpression of p16 was also found in single cases of HPV-negative SCCV (Sznurkowski Fig.…”

Section: Discussionmentioning

confidence: 99%

PD-L1 expression and survival in p16-negative and -positive squamous cell carcinomas of the vulva

Czogalla

Pham

Trillsch

et al. 2020

J Cancer Res Clin Oncol

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Aim Programmed death-ligand 1 (PD-L1) has become a widely used predictive biomarker for therapy with checkpoint inhibitors in a variety of cancers. Here, we studied the expression of PD-L1 in squamous cell carcinomas of the vulva (SCCV) with regard to HPV status via its surrogate marker p16. Additionally, the status of PD-L1 and p16 were analyzed for prognostic information and potential correlation to tumor-infiltrating lymphocytes (TILs). Methods PD-L1 was analyzed in 128 cases of SCCV using the tumor proportion score (TPS), the immune cell score (ICS) and the combined positive score (CPS). Cases were immunostained for p16 and analyzed for stromal TILs. PD-L1, p16, and TILs were compared to clinico-pathological parameters and patient's survival. Results TPS ≥ 50% and CPS ≥ 50 were correlated to a worse grading (p = 0.028 and p = 0.031), but not to FIGO-stage. CPS ≥ 50 was associated to a worse prognosis with overall survival (p = 0.021) but was not correlated to the progression-free survival. P16-positivity was correlated to a longer progression-free survival (p = 0.006) and overall survival (p = 0.023). PD-L1 expression was independent from p16 status. TILs ≥ 50% were present in 24% of the cases and were strongly correlated to PD-L1 (TPS p = 0.02, ICS p < 0.001, CPS p = 0.001). Conclusion Our data demonstrate that PD-L1 expression is frequent in SCCV and independent from p16 status. High PD-L1 expression was associated with an unfavorable outcome whereas p16-positivity turned out to be an independent positive prognostic factor.

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“…However, in our analysis, we could not find correlations between EP4 expression and p16 status in vulvar carcinoma. Multiple studies could verify p16 as a reliable surrogate for HPV-association in cervical and oropharyngeal tumors [ 37 , 38 , 39 , 40 ]. However, p16 overexpression was also detected in cases of HPV-independent tumors—this indicates that, in addition to the viral oncogenes E6/7, there must be HPV-independent pathways inducing p16 overexpression [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

EP4 as a Negative Prognostic Factor in Patients with Vulvar Cancer

Buchholz

Vattai

Fürst

et al. 2021

Cancers

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New prognostic factors and targeted therapies are urgently needed to improve therapeutic outcomes in vulvar cancer patients and to reduce therapy related morbidity. Previous studies demonstrated the important role of prostaglandin receptors in inflammation and carcinogenesis in a variety of tumor entities. In this study, we aimed to investigate the expression of EP4 in vulvar cancer tissue and its association with clinicopathological data and its prognostic relevance on survival. Immunohistochemistry was performed on tumor specimens of 157 patients with vulvar cancer treated in the Department of Obstetrics and Gynecology, Ludwig-Maximilian-University of Munich, Germany, between 1990 and 2008. The expression of EP4 was analyzed using the well-established semiquantitative immunoreactivity score (IRS) and EP4 expression levels were correlated with clinicopathological data and patients’ survival. To specify the tumor-associated immune cells, immunofluorescence double staining was performed on tissue samples. In vitro experiments including 5-Bromo-2′-Deoxyuridine (BrdU) proliferation assay and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid (MTT) viability assay were conducted in order to examine the effect of EP4 antagonist L-161,982 on vulvar carcinoma cells. EP4 expression was a common finding in in the analyzed vulvar cancer tissue. EP4 expression correlated significantly with tumor size and FIGO classification and differed significantly between keratinizing vulvar carcinoma and nonkeratinizing carcinoma. Survival analysis showed a significant correlation of high EP4 expression with poorer overall survival (p = 0.001) and a trending correlation between high EP4 expression and shorter disease-free survival (p = 0.069). Cox regression revealed EP4 as an independent prognostic factor for overall survival when other factors were taken into account. We could show in vitro that EP4 antagonism attenuates both viability and proliferation of vulvar cancer cells. In order to evaluate EP4 as a prognostic marker and possible target for endocrinological therapy, more research is needed on the influence of EP4 in the tumor environment and its impact in vulvar carcinoma.

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

Cited by 14 publications

References 37 publications

Clinico-pathological features of oropharyngeal squamous cell carcinomas in Malaysia with reference to HPV infection

Clinico-pathological features of oropharyngeal squamous cell carcinomas in Malaysia with reference to HPV infection

PD-L1 expression and survival in p16-negative and -positive squamous cell carcinomas of the vulva

EP4 as a Negative Prognostic Factor in Patients with Vulvar Cancer

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