Role of high-risk human papillomavirus in oropharyngeal squamous cell carcinoma: A clinicopathological and molecular study from a tertiary centre in India.

Dr. Amod  Kumar; Dr. Aashish   Gupta; Dr. Monica; Dr. Payal  Kumari; Dr. Sunil  Kumar

doi:10.51168/sjhrafrica.v6i12.2358

Authors

Dr. Amod Kumar Associate Professor, Department of Pathology, Nalanda Medical College, Patna, Bihar, India
Dr. Aashish Gupta Associate Professor, Department of Pathology, Nalanda Medical College, Patna, Bihar, India
Dr. Monica Associate Professor, Department of Microbiology, Motilal Nehru Medical College, Prayagraj, Uttar Pradesh, India
Dr. Payal Kumari Department of Pathology, Mahavir Cancer Sansthan, Patna, Bihar, India
Dr. Sunil Kumar Professor, Department of Pathology, Nalanda Medical College, Patna, Bihar, India

DOI:

https://doi.org/10.51168/sjhrafrica.v6i12.2358

Keywords:

Human papillomavirus, Oropharyngeal squamous cell carcinoma, Polymerase chain reaction, E6/E7 oncoproteins

Abstract

Background

High-risk human papillomavirus (hrHPV) has emerged as a major etiological agent in a biologically distinct subset of oropharyngeal squamous cell carcinoma (OPSCC), associated with improved clinical outcomes. However, Indian data on HPV-associated OPSCC remain heterogeneous and limited.

Objective

To determine the prevalence of hrHPV-driven OPSCC and evaluate its clinicopathological, molecular, and prognostic correlates.

Methods

A retrospective cross-sectional study was conducted at a single tertiary care teaching hospital in eastern India. Consecutive primary OPSCC cases diagnosed between January 2020 and December 2023 were analyzed. p16 immunohistochemistry was used as a screening tool, followed by hrHPV DNA polymerase chain reaction (PCR). Discordant cases underwent E6/E7 mRNA analysis when tissue permitted. Clinicopathological parameters and progression-free survival were evaluated.

Results

Among 180 OPSCC cases, hrHPV positivity was identified in 52.2%. HPV-positive tumors were significantly associated with younger age, lower tobacco exposure, non-keratinizing morphology, lower T stage, higher nodal stage, and superior two-year progression-free survival (81% vs. 65%, p=0.03).

Conclusion

hrHPV-driven OPSCC constitutes a substantial proportion of OPSCC in India. Integrated p16 and molecular testing offers reliable classification with important prognostic implications.

Recommendations

Routine p16 screening with confirmatory molecular testing should be incorporated into OPSCC diagnostic protocols. Prospective multicentric Indian studies are recommended.

References

WHO Classification of Tumours Editorial Board. Head and Neck Tumours. 5th ed. Lyon: International Agency for Research on Cancer (IARC); 2022.

Gupta B, Johnson NW, Kumar N. Global epidemiology of head and neck cancers: A continuing challenge. Lancet Oncol. 2016;17(11): e451-e460.

Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24-35. https://doi.org/10.1056/NEJMoa0912217

Gillison ML, D'Souza G, Westra W, et al. Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst. 2008;100(6):407-420. https://doi.org/10.1093/jnci/djn025

Münger K, Baldwin A, Edwards KM, et al. Mechanisms of human papillomavirus-induced oncogenesis. Oncogene. 2004;23(38):6767-6778.

Fakhry C, Westra WH, Li S, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Clin Oncol. 2008;26(8):1338-1344. https://doi.org/10.1093/jnci/djn011

Westra WH. The morphologic profile of HPV-related head and neck squamous carcinoma: Implications for diagnosis, prognosis, and clinical management. Head Neck Pathol. 2012;6(Suppl 1):S48-S54. https://doi.org/10.1007/s12105-012-0371-6

O'Sullivan B, Huang SH, Siu LL, et al. Deintensification candidate subgroups in human papillomavirus-related oropharyngeal cancer according to minimal risk of distant metastasis. J Clin Oncol. 2013;31(5):543-550. https://doi.org/10.1200/JCO.2012.44.0164

Mehanna H, Beech T, Nicholson T, et al. Prevalence of human papillomavirus in oropharyngeal and nonoropharyngeal head and neck cancer-systematic review and meta-analysis of trends by time and region. Head Neck. 2013;35(5):747-755. https://doi.org/10.1002/hed.22015

Ramesh G, Katkuri S, Babu PK, et al. Prevalence of HPV in oropharyngeal squamous cell carcinoma in South India. Indian J Cancer. 2015;52(4):571-574.

Nair S, Pillai MR. Human papillomavirus and disease mechanisms: relevance to oral and cervical cancers. Indian J Med Res. 2017;146(4):398-404.

Gillison ML, Chaturvedi AK, Anderson WF, Fakhry C. Epidemiology of human papillomavirus-positive head and neck squamous cell carcinoma. J Clin Oncol. 2015;33(29):3235-3242. https://doi.org/10.1200/JCO.2015.61.6995

Dahlstrom KR, Garden AS, William WN Jr, et al. Epidemiology of HPV-associated oropharyngeal cancer. Cancer. 2015;121(15):2635-2644.

Chaturvedi AK, Engels EA, Pfeiffer RM, et al. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011;29(32):4294-4301. https://doi.org/10.1200/JCO.2011.36.4596

Prigge ES, Arbyn M, von Knebel Doeberitz M, Reuschenbach M. Diagnostic accuracy of p16INK4a immunohistochemistry in oropharyngeal squamous cell carcinomas: A systematic review and meta-analysis. Int J Cancer. 2017;140(5):1186-1198. https://doi.org/10.1002/ijc.30516

Mirghani H, Amen F, Blanchard P, et al. Treatment de-escalation in HPV-positive oropharyngeal carcinoma: Ongoing trials, critical issues and perspectives. Ann Oncol. 2015;26(4):647-656. https://doi.org/10.1002/ijc.28847

Lewis JS Jr. p16 immunohistochemistry as a standalone test for risk stratification in oropharyngeal squamous cell carcinoma. Arch Pathol Lab Med. 2012;136(7):766-772. https://doi.org/10.1007/s12105-012-0369-0

Rietbergen MM, Brakenhoff RH, Bloemena E, et al. Human papillomavirus detection and comorbidity: Critical issues in selection of patients with oropharyngeal cancer for treatment de-escalation trials. Int J Cancer. 2014;135(3):572-580.

El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ (eds). WHO Classification of Head and Neck Tumours. 4th ed. Lyon: IARC; 2017.

Licitra L, Perrone F, Bossi P, et al. High-risk human papillomavirus affects prognosis in patients with surgically treated oropharyngeal squamous cell carcinoma. Ann Oncol. 2015;26(2):376-381.

Garden AS, Harris J, Vokes EE, et al. Preliminary results of RTOG 0129: A phase III trial comparing standard radiation therapy with accelerated fractionation in head and neck cancer. Radiother Oncol. 2013;109(1):1-7.

Mehanna H, Robinson M, Hartley A, et al. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): An open-label randomised controlled phase 3 trial. Lancet. 2019;393(10166):51-60. https://doi.org/10.1016/S0140-6736(18)32752-1

Amin MB, Edge SB, Greene FL, et al. AJCC Cancer Staging Manual. 8th ed. New York: Springer; 2017.

College of American Pathologists. Protocol for the examination of specimens from patients with carcinomas of the pharynx. CAP; 2018.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Head and Neck Cancers. Version 1.2023.