Expression of Human Papillomavirus-Related Proteins and Its Clinical Implication in Tonsillar Squamous Cell Carcinoma

Abstract

BackgroundHuman papillomavirus (HPV) is known to cause of oropharyngeal squamous cell carcinoma (SqCC). HPV positive SqCCs overexpress p16 and are associated with better survival. Several markers of cell cycles and apoptosis have been reported as a prognostic value. We examined the prognostic value of HPV status, p16, cyclin D1, and Bcl-2 in patients with tonsillar SqCC.MethodsTissue microarrays were constructed in 56 cases of tonsillar SqCC for which we performed an immunohistochemistry and an in situ hybridization (ISH) of the HPV.ResultsOf the 56 cases, 31 (55.3%) were positive for p16 and 20 (35.7%) were positive for HPV ISH. The expressions of p16, cyclin D1, and Bcl-2 were not correlated with the clinicopathologic variables including smoking status, differentiation and pT- and pN-stages. The HPV ISH positive group showed a better overall survival than the HPV negative group (p=0.04), and the p16 positive group showed a better disease free survival (DFS) than the negative group (p=0.016). Cox regression analysis showed that only p16 positivity was an independent prognostic factor for DFS (p=0.03; hazard ratio, 10.1).ConclusionsOur results indicate that both p16 expression and HPV status are useful indicators for risk stratification in patients with tonsillar SqCC.

Human Papillomavirus Prevalence and Cell Cycle Related Protein Expression in Tonsillar Squamous Cell Carcinomas of Korean Patients with Clinicopathologic Analysis

“…Robinson et al22 found 5% of p16-positive/HPV ISH-negative results in six studies examining 496 oropharyngeal squamous cell carcinomas, while Song et al9 reported a greater number of p16-positive/HPV ISH-negative cases at 27.6% (13/47) in Koreans. The high proportion of p16-positive/HPV ISH-negative cases in our results (19.1%, 17/89) together with the result of Song et al9 suggest that this considerably high incidence of p16-positive/HPV ISH-negative cases may be a distinguishing feature of TSCC in Koreans. Furthermore, in light of these results, there are limitations in using p16 as a surrogate marker for judging HPV infection status.…”

“…Methodologically, there may be yet unidentified HPV genotypes that current HPV-specific tests cannot detect and do not contain the consensus DNA sequences detectable by ISH, PCR, or genotyping 19. Robinson et al22 found 5% of p16-positive/HPV ISH-negative results in six studies examining 496 oropharyngeal squamous cell carcinomas, while Song et al9 reported a greater number of p16-positive/HPV ISH-negative cases at 27.6% (13/47) in Koreans. The high proportion of p16-positive/HPV ISH-negative cases in our results (19.1%, 17/89) together with the result of Song et al9 suggest that this considerably high incidence of p16-positive/HPV ISH-negative cases may be a distinguishing feature of TSCC in Koreans.…”

Human papillomavirus‐stratified analysis of the prognostic role of miR‐21 in oral cavity and oropharyngeal squamous cell carcinoma

“…In contrast, the incidence of oropharyngeal squamous cell carcinoma (OPSCC) has increased in recent decades . Strong evidence suggests that human papilloma virus (HPV) is associated with HNSCC, particularly OPSCC . HPV, especially type 16, is responsible for up to 80% of OPSCC and a small subgroup of oral squamous cell carcinoma (OSCC) …”

“…HPV‐related HNSCC has a molecular, epidemiological, and clinical profile that is distinct from classical tobacco and/or alcohol‐associated HNSCCs. Recent clinical trials demonstrated that HPV‐related HNSCC was associated with younger age, smaller primary tumors, more advanced lymph node metastasis, and better prognosis compared with non‐HPV‐related HNSCC . These distinct clinical outcomes may be related primarily to the different molecular pathogenesis of the two tumor types.…”

“…2 Strong evidence suggests that human papilloma virus (HPV) is associated with HNSCC, particularly OPSCC. 3 HPV, especially type 16, is responsible for up to 80% of OPSCC and a small subgroup of oral squamous cell carcinoma (OSCC). 2,3 HPV-related HNSCC has a molecular, epidemiological, and clinical profile that is distinct from classical tobacco and/or alcohol-associated HNSCCs.…”