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Detection of Human Papillomavirus and p16INK4a Expression in Thai Patients with Oral Squamous Cell Carcinoma

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Abstract

This study investigated the prevalence of human papillomavirus (HPV) infection in oral squamous cell carcinoma (OSCC) cases, as well as the association between HPV presence and p16INK4a expression, in Thai patients with OSCC. Eighty-one formalin-fixed paraffin-embedded specimens of OSCC were obtained. DNA extraction was performed; this was followed by nested polymerase chain reaction analysis to determine HPV DNA status, using consensus primers for the L1 region of HPV. HPV subtypes were determined by DNA sequencing. HPV-positive specimens and HPV-negative specimens from age- and sex-matched patients were subjected to immunohistochemical analysis to determine p16INK4a expression status. Of the 81 OSCC specimens, eight (9.9%) exhibited HPV DNA; DNA sequencing confirmed that the viral subtype was HPV-18 in all eight specimens. These eight HPV-positive specimens, as well as eight HPV-negative specimens from age- and sex-matched patients, were subjected to immunohistochemical analysis to determine p16INK4a expression status. Three of eight (37.8%) HPV-positive specimens and three of eight (37.8%) HPV-negative specimens showed positive p16INK4a expression findings. However, we did not find a significant association between HPV status and p16INK4a expression status in our OSCC samples. In conclusion, the prevalence of high-risk HPV was low in this group of OSCC patients; no association between HPV status and p16INK4a expression status was identified.

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Data Availability

The data presented in this study are available on request from the corresponding author. The data are not publicly available because of ethical restrictions.

Code Availability

Not applicable.

Abbreviations

HPV:

Human papillomavirus

OSCC:

Oral squamous cell carcinoma

CDK:

Cyclin-dependent kinase

FFPE:

Formalin-fixed paraffin-embedded

IHC:

Immunohistochemistry

PCR:

Polymerase chain reaction

OPSCC:

Oropharyngeal squamous cell carcinoma

References

  1. Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45:309–16.

    Article  Google Scholar 

  2. El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ. World Health Organization classification of head and neck tumours. 4th ed. Lyon: IARC; 2017.

    Google Scholar 

  3. Metgud R, Astekar M, Verma M, Sharma A. Role of viruses in oral squamous cell carcinoma. Oncol Rev. 2012;6:e21.

    Article  Google Scholar 

  4. Luo GG, Ou JH. Oncogenic viruses and cancer. Virol Sin. 2015;30:83–4.

    Article  Google Scholar 

  5. Shaikh MH, McMillan NA, Johnson NW. HPV-associated head and neck cancers in the Asia Pacific: a critical literature review & meta-analysis. Cancer Epidemiol. 2015;39:923–38.

    Article  Google Scholar 

  6. Khovidhunkit SO, Buajeeb W, Sanguansin S, Poomsawat S, Weerapradist W. Detection of human papillomavirus in oral squamous cell carcinoma, leukoplakia and lichen planus in Thai patients. Asian Pac J Cancer Prev. 2008;9:771–5.

    PubMed  Google Scholar 

  7. Phusingha P, Ekalaksananan T, Vatanasapt P, Loyha K, Promthet S, Kongyingyoes B, et al. Human papillomavirus (HPV) infection in a case-control study of oral squamous cell carcinoma and its increasing trend in northeastern Thailand. J Med Virol. 2017;89:1096–101.

    Article  CAS  Google Scholar 

  8. Chaisrisawadisuk S, Sa-Nguanraksa D, Thumrongtaradol T, O-charoenrat P. Prevalence of human papilloma virus in head and neck cancer in Thai population. J Med Assoc Thai. 2020;103:37–41.

    Google Scholar 

  9. Potaporn M, Apipan P, Suphanpayak S. Prevalence of human papillomavirus 16&18 in oral cavity and oropharyngeal squamous cell carcinoma in Rajavithi hospital. J Med Assoc Thai. 2018;101:1–8.

    Google Scholar 

  10. Sritippho T, Pongsiriwet S, Lertprasertsuke N, Buddhachat K, Sastraruji T, Iamaroon A. p16 - a possible surrogate marker for high-risk human papillomaviruses in oral cancer? Asian Pac J Cancer Prev. 2016;17:4049–57.

    PubMed  Google Scholar 

  11. Chotipanich A, Siriarechakul S, Mungkung OO. Role of high-risk human papillomavirus in the etiology of oral and oropharyngeal cancers in Thailand: a case-control study. SAGE Open Med. 2018;6:2050312118765604.

    Article  Google Scholar 

  12. Komolmalai N, Pongsiriwet S, Lertprasertsuke N, Lekwanavijit S, Kintarak S, Phattarataratip E, et al. Human papillomavirus 16 and 18 infection in oral cancer in Thailand: a multicenter study. Asian Pac J Cancer Prev. 2020;21:3349–55.

    Article  CAS  Google Scholar 

  13. Lewis JS Jr. Human papillomavirus testing in head and neck squamous cell carcinoma in 2020: where are we now and where are we going? Head Neck Pathol. 2020;14:321–9.

    Article  Google Scholar 

  14. Pannone G, Rodolico V, Santoro A, Lo Muzio L, Franco R, Botti G, et al. Evaluation of a combined triple method to detect causative HPV in oral and oropharyngeal squamous cell carcinomas: p16 immunohistochemistry, consensus PCR HPV-DNA, and in situ hybridization. Infect Agent Cancer. 2012;7:4.

    Article  CAS  Google Scholar 

  15. Hernandez BY, Lynch CF, Chan OTM, Goodman MT, Unger ER, Steinau M, et al. Human papillomavirus DNA detection, p16(INK4a), and oral cavity cancer in a U.S. population. Oral Oncol. 2019;91:92–6.

    Article  CAS  Google Scholar 

  16. Minami K, Kogashiwa Y, Ebihara Y, Nakahira M, Sugasawa M, Fujino T, et al. Human papillomavirus and p16 protein expression as prognostic biomarkers in mobile tongue cancer. Acta Otolaryngol. 2017;137:1121–6.

    Article  CAS  Google Scholar 

  17. Bumalee D, Lapthanasupkul P, Tamboon E, Aittiwarapoj A, Klongnoi B, Kitkumthorn N. Low frequency of human papillomavirus and Epstein-Barr virus DNA in ameloblastoma of Thai patients. World J Dent. 2020;11:446–50.

    Article  Google Scholar 

  18. Boonmongkolraksa P, Doungudomdacha S, Surarit R, Khovidhunkit SO. Survey of human papilloma prevalence in the oral cavity of Thai dental patients. Southeast Asian J Trop Med Public Health. 2020;51:640–9.

    Google Scholar 

  19. Lewis JS Jr, Beadle B, Bishop JA, Chernock RD, Colasacco C, Lacchetti C, et al. Human papillomavirus testing in head and neck carcinomas: guideline from the College of American Pathologists. Arch Pathol Lab Med. 2018;142:559–97.

    Article  Google Scholar 

  20. Jalouli M, Jalouli J, Ibrahim SO, Hirsch JM, Sand L. Comparison between single PCR and nested PCR in detection of human papilloma viruses in paraffin-embedded OSCC and fresh oral mucosa. Vivo. 2015;29:65–70.

    CAS  Google Scholar 

  21. Zafereo ME, Xu L, Dahlstrom KR, Viamonte CA, El-Naggar AK, Wei Q, et al. Squamous cell carcinoma of the oral cavity often overexpresses p16 but is rarely driven by human papillomavirus. Oral Oncol. 2016;56:47–53.

    Article  CAS  Google Scholar 

  22. Nopmaneepaisarn T, Tangjaturonrasme N, Rawangban W, Vinayanuwattikun C, Keelawat S, Bychkov A. Low prevalence of p16-positive HPV-related head-neck cancers in Thailand: tertiary referral center experience. BMC Cancer. 2019;19:1050.

    Article  Google Scholar 

  23. Klingenberg B, Hafkamp HC, Haesevoets A, Manni JJ, Slootweg PJ, Weissenborn SJ, et al. p16 INK4A overexpression is frequently detected in tumour-free tonsil tissue without association with HPV. Histopathology. 2010;56:957–67.

    Article  Google Scholar 

  24. Evans MF, Matthews A, Kandil D, Adamson CS, Trotman WE, Cooper K. Discrimination of ‘driver’ and ‘passenger’ HPV in tonsillar carcinomas by the polymerase chain reaction, chromogenic in situ hybridization, and p16(INK4a) immunohistochemistry. Head Neck Pathol. 2011;5:344–8.

    Article  Google Scholar 

  25. Singhi AD, Westra WH. Comparison of human papillomavirus in situ hybridization and p16 immunohistochemistry in the detection of human papillomavirus-associated head and neck cancer based on a prospective clinical experience. Cancer. 2010;116:2166–73.

    PubMed  Google Scholar 

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Acknowledgements

The authors thank Mr. Eakapong Tamboon, Ms. Jintana Pankam, Dr. Khin Mya Tun, and Mr. Dusit Bumalee for technical assistance. We also thank Gabrielle White Wolf, Ph.D. and Ryan Chastain-Gross, Ph.D., from Edanz (https://www.edanz.com/ac) for editing a draft of this manuscript.

Funding

This work was supported by Mahidol University research grant (051/2562) to Siribang-on Piboonniyom Khovidhunkit, Boworn Klongnoi, and Vanvisa Sresumatchai under the Development of Disease Management Model for Oral Cancer with an Integration Network of Screening, Surveillance, and Treatment in Northeast Health District project.

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Authors and Affiliations

  1. Department of Oral Medicine and Periodontology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand

    Dulyapong Rungraungrayabkul & Naruemon Panpradit

  2. Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand

    Puangwan Lapthanasupkul

  3. Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand

    Nakarin Kitkumthorn

  4. Department of Oral Biomedical Sciences, Division of Oral Diagnosis, Research Group of Chronic Inflammatory Oral Diseases and Systemic Diseases associated with Oral Health, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand

    Poramaporn Klanrit & Ajiravudh Subarnbhesaj

  5. Development of Disease Management Model for Oral Cancer with an Integration Network of Screening, Surveillance, and Treatment in Northeast Health District Project, Mahidol University, Bangkok, Thailand

    Vanvisa Sresumatchai, Boworn Klongnoi & Siribang-on Piboonniyom Khovidhunkit

  6. Department of Biostatistics, Faculty of Public Health, Mahidol University, Bangkok, Thailand

    Vanvisa Sresumatchai

  7. Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Mahidol University, Bangkok, Thailand

    Boworn Klongnoi

  8. Department of Advanced General Dentistry, Faculty of Dentistry, Mahidol University, 6 Yothi Rd. Rajthewee, Bangkok, 10400, Thailand

    Siribang-on Piboonniyom Khovidhunkit

Authors
  1. Dulyapong Rungraungrayabkul
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  2. Naruemon Panpradit
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  3. Puangwan Lapthanasupkul
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  4. Nakarin Kitkumthorn
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  5. Poramaporn Klanrit
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  6. Ajiravudh Subarnbhesaj
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  7. Vanvisa Sresumatchai
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  8. Boworn Klongnoi
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  9. Siribang-on Piboonniyom Khovidhunkit
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Contributions

DR: performed all experiments, performed data analysis, and wrote the manuscript. NP: reviewed the manuscript for important intellectual content. PL: prepared specimens, performed some experiments, and reviewed the manuscript for important intellectual content. NK: supplied some materials and reviewed the manuscript for important intellectual content. PK: prepared some OSCC specimens and provided clinical data. AS: prepared some OSCC specimens and provided clinical data. VS: supplied research funding. BK: supplied research funding, prepared some OSCC specimens, and provided clinical data. SPK: conceptualized the overall research aims, designed the experiments, prepared the manuscript for publication, and supplied research funding.

Corresponding author

Correspondence to Siribang-on Piboonniyom Khovidhunkit.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Consent to Participate

No informed consent was required for this study because only pathology slides were used.

Consent for Publication

Not applicable.

Ethical Approval

The study was performed in accordance with the principles of the Declaration of Helsinki. This study was approved by the Faculty of Dentistry/Faculty of Pharmacy, Mahidol University, Institutional Review Board (COA.No.MU-DT/PY-IRB 2019/037.1806 and MU-DT/PY-IRB 2019/041.0307) and the Center for Ethics in Human Research, Khon Kaen University (IRB00001189).

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Rungraungrayabkul, D., Panpradit, N., Lapthanasupkul, P. et al. Detection of Human Papillomavirus and p16INK4a Expression in Thai Patients with Oral Squamous Cell Carcinoma. Head and Neck Pathol 16, 444–452 (2022). https://doi.org/10.1007/s12105-021-01381-x

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  • DOI: https://doi.org/10.1007/s12105-021-01381-x

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