Staging and prognosis of oropharyngeal carcinoma according to the 8th Edition of the American Joint Committee on Cancer Staging Manual in human papillomavirus infection

Abstract

PurposeThe aim of this study was to evaluate the 8th edition of the American Joint Committee on Cancer Staging Manual: Head and Neck Section on oropharyngeal squamous cell cancer (OPSCC) and to clarify the relationship between p16 overexpression and the presence of human papillomavirus (HPV) DNA using fresh frozen samples.MethodsSamples from 100 OPSCC patients were analyzed using polymerase chain reaction (PCR) and p16 immunohistochemistry.ResultsFive-year overall survival (OS) was 73.0%, 93.9%, and 62.2% in all, p16-positive (n = 34), and p16-negative (n = 66) cases, respectively. OS tended to be better aligned with stage in the 8th edition than in the 7th edition. The 5-year OS was 96.0% in never or light smokers (< 40 pack-years), and 87.5% in heavy smokers (≥ 40 pack-years) in the p16-positive group, respectively (p = 0.027). HPV infection was found in 100% of p16-positive and 21.2% of p16-negative cases. The p16-positive cases had higher viral load and integrated physical status than the p16-negative cases. Although 1 case with p16 overexpression showed no PCR amplification using consensus primers, PCR amplification was detected using HPV 16 E6-specific primers.ConclusionsThe 8th edition predicts OPSCC prognosis more accurately than the 7th edition and p16-overexpression is an excellent surrogate marker for detecting HPV infection. Although high-risk-type HPV infection was observed in p16-negative cases, it showed no significant effect in survival outcome.

Prognostic impact of additional HPV diagnostics in 102 patients with p16-stratified advanced oropharyngeal squamous cell carcinoma

“…Previous studies already indicated that different constellations of the p16-and HPV-status can define further prognostic divergent subgroups within OPSCCs [19][20][21][22][23][24]. Nevertheless, studies reporting long-term oncologic results of subgroups defined by p16-and HPV-status combined are rare [19][20][21][22][23][24], even though a meta-analysis by Albers et al included 24 studies that investigated the survival of patients with HNSCC and evaluated p16-and HPV-status [24]. A comparison of our study with this meta-analysis seems limited due to the following reasons: only 13 of the included studies selectively focused on OPSCCs, and only two of them provided the 5-year survival estimates of patients treated with curative intent, with no cases of distant metastases included [21,38].…”

“…Therefore, it was previously used as a surrogate marker for identification of HPV-associated OPSCCs [17,18]. Nevertheless, previous studies suggest that the combination of both markers, p16-and HPV-status, define prognostic divergent subgroups [19][20][21][22][23][24]. This needs to be considered, especially since treatment de-intensification trials investigated altered therapeutic regimes for HPV-associated OPSCCs [17,25].…”

Raptor and rictor expression in patients with human papillomavirus-related oropharyngeal squamous cell carcinoma

“…Head and neck cancer is the sixth most common cancer worldwide, accounting for approximately 5% of all cancer cases (12). Excessive alcohol consumption and smoking are well-known risk factors for head and neck cancer (13,14). Although alcohol and tobacco use have decreased in recent years, the incidence of oropharyngeal cancer has nevertheless continued to increase (15).…”

“…The main cause of this phenomenon is the increase in the incidence of human papillomavirus (HPV)-related oropharyngeal cancer arising in the tonsillar region and the base of the tongue (16). HPV-related oropharyngeal squamous cell carcinoma (OPSCC) has a significantly better survival rate compared with other forms of OPSCC (14,17,18). The clinical staging system for OPSCC separates HPV-related cancer from HPV-unrelated cancer in the 8th edition American Joint Committee on Cancer (AJCC) TNM classification (18,19).…”

“…Ethical approval was obtained from the University of the Ryukyus Research Ethics Committee, and informed consent was obtained from each patient.All tissue samples from primary lesions were analyzed with PCR using fresh frozen samples and p16 immunohistochemistry using formalin-fixed paraffin-embedded samples. The detection methods have been published in detail previously(14,16). The cutoff point for p16 overexpression was diffuse (≥ 75%) tumor expression, with at least moderate (+ 2/3) staining intensity according to the 8th edition of the AJCC.…”