Demographic Profile of p16 Immunopositive and HPV DNA PCR Positive Oral Squamous Cell Carcinoma in a Large Cohort of Indian Patients

Abstract

Background:The Indian subcontinent has the highest incidence of oral cavity squamous cell carcinoma in the world. The high incidence of tobacco chewing habit with or without smoking has been found to be the chief culprit. However in a minor subset of patients Human Papilloma Virus may play a role. Materials and Methods: A total of 800 cases of Oral squamous cell carcinoma were included in the study. The patients were given a questionnaire comprising of questions about demographic details and habits. The biopsy samples were routinely processed for immunohistochemistry for p16 (E6H4 clone, CINtec histology, Roche diagnostics). Cases with 2+/3+ positive nuclear staining with more than 75% cells immunopositive were taken as p16 immunopositive as per the AJCC criteria and were further subjected to HPV DNA PCR for which DNA was extracted from the formalin fixed paraffin embedded tissue. Results: Out of 800 OSCC cases 139 (17.37%) showed p16 immunopositivity by AJCC criteria. Out of these, 104 (104/139, 74.8%) cases were positive by HPV DNA PCR for HPV-16/18. Following patient characteristics were associated with a higher proportion of p16 and HPV DNA positivity-urban residence, vegetarian diet, illiteracy, graduate or higher education. No correlation was noted with gender, tobacco smoking or chewing habits, religion, occupation or site of tumor. The p16 immunopositivity was higher in the younger age group with no tobacco habits. Conclusion: A significant proportion of OSCC cases in India are associated with HPV infection. A higher percentage of p16 immunopositivity amongst younger patients with no tobacco habits points towards a distinct subset of patients in whom HPV may be the chief culprit and not just playing a supporting role.

Expression of P16 in Various Grades of Oral Squamous Cell Carcinoma of Tertiary Care Hospitals of Peshawar

“…A study conducted by Belobrov et al in 2018 also showed that male (57%) had more p16 positivity than females (43%) (23). In contrast to our results Naz et al in 2022 found no significant association of p16 expression with gender of the patients (24).…”

“…In accordance to our results, a study conducted by Agarwal et al, in 2021 found no significant association between grades of OSCC and p16 expression (25). In contrast to our results, a study conducted by Naz et al in 2022 showed that the most of the OSCC cases with p16 positivity were found in the moderately differentiated (79.5%) followed by well and poorly differentiated OSCC (24). CONCLUSION 1 p16 expression in various grades of OSCC showed no significance association.…”

The Prevalence of HPV in Oral Cavity Squamous Cell Carcinoma

“…Thirty-one studies met the inclusion criteria, comprising 5007 patients with OCSCC from 24 different countries. Sixteen studies were from Asia [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ], eight from Europe [ 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ], two from Africa [ 43 , 44 ], two from South America [ 35 , 45 ], two from North America [ 46 , 47 ], and one from Asian Pacific [ 48 ]. The study size ranged from 17 patients in a study from Uganda [ 44 ] to 940 patients in the Netherlands [ 41 ].…”

“…Five studies ( n = 112) reported the mean age of patients with HPV+ OCSCC varying from 53 to 63 years. Two studies reported that HPV+ OCSCC was significantly associated with a lower mean age than HPV-negative (HPV−) OCSCC ( n = 59) [ 38 , 41 ] while five studies found it statistically insignificant [ 24 , 27 , 28 , 30 , 45 ]. The mean age in HPV−OCSCC ranged from 57.5–64 years [ 37 , 38 , 41 , 45 , 49 ].…”

“…The female-to-male ratio varied from 1:1 in the Republic of Korea to 1:8 in Réunion Island among patients with OCSCC [ 23 , 48 ]. Three studies reported a significant association between patients with HPV+ OCSCCs and the male gender [ 37 , 41 , 49 ], whereas no association was reported in five studies [ 24 , 27 , 28 , 30 , 45 ].…”