Histopathological analysis of oral squamous cell carcinoma in nonsmokers and nondrinkers

Abstract

A distinct clinical subgroup of nonsmoking (NS) and nondrinking (ND) patients with oral squamous cell carcinoma (OSCC) has been identified. The objective of the study was to assess this cohort for molecular variations in the disease process and if these could be attributed to clinical or epidemiological characteristics. One hundred and twenty-nine consecutive patients (71 males, 58 females) treated for OSCC were assessed at the Royal Melbourne Hospital between January 2007 and July 2010. Formalin-fixed paraffin embedded (FFPE) sections were stained for p53, p16, cyclin D1, and epidermal growth factor receptor (EGFR). Biomarker overexpression was observed in 72 (56%) cases for p53, 23 (18%) for p16, 45 (35%) for cyclin D1, and 72 (56%) for EGFR. Multiple logistic regression analysis revealed that tongue tumors (p ¼ 0.012) and late stage cancers (p ¼ 0.031) were more likely to have cyclin D1 overexpression. Further, older patients significantly more often had cyclin D1 overexpression (p ¼ 0.008) and NSND patients had more p16 expression (p ¼ 0.043). In contrast, smokers were more likely to have EGFR overexpression (p ¼ 0.033). Concurrent overexpression of p53 and cyclin D1 were observed (p ¼ 0.030). Smoking, site, and stage of OSCC can influence biomarker expression, with p16 overexpression specifically observed in NSND, indicating fundamental differences in the mechanisms of oral carcinogenesis among different patient cohorts.

The role of human papillomavirus in p16‐positive oral cancers

“…Expression levels of p16 were determined by IHC staining using p16 mouse monoclonal antibody (Roche, Basel, Switzerland). The staining was scored as previously described …”

“…In a previous study, we performed retrospective immunohistochemical (IHC) staining to determine the expression of several proteins in 129 formalin‐fixed paraffin‐embedded (FFPE) specimens from a well‐defined cohort of consecutive oral squamous cell carcinoma (OSCC) patients. We found 23 (18%) of these patients displayed p16 overexpression, which was significantly increased in non‐smokers and non‐drinkers who were less than 70 years old.…”

EGFR/PI3K/Akt/mTOR pathway in head and neck squamous cell carcinoma patients with different HPV status

“…Some authors, similar to us, did not find significant relation between EGFR expression and patient's age, smoking and alcohol abuse [17,27,28], TN stages [17,21,22], grade [21] or degree of keratinization [19]. However, some researchers reported contrary results, demonstrating significant higher percentage of tumors with EGFR overexpression in older patients [20], smokers [21,29] and among T3-T4 cancers [19] as compared, respectively, to younger patients, non-smokers or tumors with lower T stage. Other authors found significant correlation between EGFR expression and grade, i.e.…”

Molecular drivers of oral cavity squamous cell carcinoma in non-smoking and non-drinking patients: what do we know so far?

“…62 In a larger study, Belobrov et al performed immunohistochemical staining for biomarkers such as p53, p16, cyclin D1, and EGFR using samples from 129 OCSCC patients. 58 While overexpression of these biomarkers was seen in many of the analyzed specimens, p16 overexpression was significantly stronger in NSND cases under the age of 70. Expression of p16 has been used as a proxy for HPV-associated oncogenesis, as inactivation of Rb by the HPV viral protein E7 leads to p16 upregulation.…”

“…HPV infection is hypothesized to be a contributing factor to the increasing rates of OCSCC in NSND patients, analogous to HPVassociated OPSCC. [56][57][58] It is acknowledged that patients with HPVassociated OPSCC have a distinct epidemiologic profile, with younger age at presentation, absence of strong smoking history, and higher socioeconomic status. The etiologic contribution of HPV in OCSCC is less understood.…”