Biologic importance and prognostic significance of selected clinicopathological parameters in patients with oral and oropharyngeal squamous cell carcinoma, with emphasis on smoking, protein p16INK4a expression, and HPV status

Abstract

The aim of this study is to evaluate the biologic importance and prognostic significance of selected clinicopathological parameters in patients with oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinoma, with emphasis on smoking, protein p16INK4a (p16) expression, and human papillomavirus (HPV) status. The study sample consisted of 48 patients with OSCC and 44 patients with OPSCC. Half of the patients were nonsmokers and the other half were gender-, age-and tumor localization-matched smokers.p16 expression was detected in 17/48 (35 %) OSCCs and in 36/44 (82 %) OPSCCs and HPV DNA was present in 7/48 (15 %) OSCCs and in 35/44 (80 %) OPSCCs. The sensitivity and specificity of p16 expression for HPV DNA presence were 0.74 and 0.88, respectively.The OPSCCs were more frequently basaloid (p < 0.001) while the OSCCs were more frequently conventional (p < 0.000001). The OSCCs were more likely to recur locally and to be the cause of death (p = 0.009 in both parameters).The HPV-positive tumors were more frequently localized in oropharynx, were basaloid SCCs and were p16-and HPV-positive (p < 0.000001 in all 4 parameters). The HPV-negative tumors were more frequently localized in oral cavity (p < 0.000001), more frequently asociated with local, regional and locoregional recurence (p = 0.011, p = 0.019 and p = 0.030, respectively) and with tumor-related death (p = 0.003). There was no significant difference with regard to smoking history (p > 0.05).The survival of patients with HPV-positive tumors was significantly longer (median 112 months; 95% CI 54 -112 months) than that of patients with HPV-negative tumors (median 17 months; 95% CI 12 -39 months) (p < 0.001).The HPV status of OSCC/OPSCC is an important biological and prognostic parameter and should be examined in all cases, using PCR or immunohistochemical detection of surrogate marker p16. Smoking itself does not seem to be an important prognostic factor.

The presence of high-risk human papillomavirus (HPV) E6/E7 mRNA transcripts in a subset of sinonasal carcinomas is evidence of involvement of HPV in its etiopathogenesis

“…HR-HPV is an important risk factor for a subset of head and neck cancer, particularly in oropharyngeal SCC with highly variable detection rates, reaching up to 80 % [12,13,39,40]. HPV-positive oropharyngeal SCC usually affects slightly younger patients, nonsmokers or light smokers, nondrinkers, patients with good oral hygiene, and probably higher (oral) sexual exposure [11].…”

“…Regarding the latter, oropharyngeal SCC, affecting mostly the palatine tonsils and root of the tongue, shows the strongest, although highly variable association with HR-HPV infection [11][12][13]. In sinonasal carcinoma, HPV detection rates vary significantly from 0 to 100 % [2,[14][15][16][17][18][19][20].…”

Do high-risk human papillomaviruses cause oral cavity squamous cell carcinoma?

“…Many studies [16][17][18][19][20][21][22][23][24][25][26][27][28][29] have identified a high proportion of OCSCC with detectable HPV DNA (Table 1). In a recent systematic review, summarizing 60 publications on 4195 patients with OCSCC, Isayeva et al [30] found that 705 (16.8%) of these tumors contained HPV DNA especially the HPV16 genotype.…”

Prognostic utility of basaloid differentiation in oropharyngeal cancer

“…Basaloid differentiation is anecdotally noted by some pathologists to be associated with p16 positivity. This association, however, has not been adequately quantified in the literature [3,11,12,15], nor has the prognostic implications of basaloid differentiation been described.…”