The Eighth AJCC head and neck cancer staging criteria were used to evaluate positive P16 expression (moderate/strong nuclear expression intensity and distribution >75% cells) in NSCLC.
The association between p16 positivity, regression grade and improved survival provides a rationale for de-intensification strategies in patients with head and neck cancer who respond well to neoadjuvant therapy, a concept that is being tested in prospective clinical trials.
To analyze quality of life (QOL) and performance status (PS) for head and neck cancer (HNC) patients treated on NRG Oncology RTOG 0129 by treatment (secondary outcome) and p16 status, and to examine the association between QOL/PS and survival.
In a subset of 162 patients with both HPV serology and p16 immunohistochemical (IHC) measures available, both measures were similarly associated with survival in the oropharynx (HR for serology, 0.16; 95% CI, 0.03-0.47; for p16 measures, 0.16; 95% CI, 0.03-0.46), whereas only serology was associated with outcome when considering all head and neck cancer cases (HR for serology,0.49; 95% CI, 0.23-1.04; for p16, 0.65; 95% CI, 0.30-1.42).
We tested formalin-fixed paraffin-embedded diagnostic biopsies for p16 immunohistochemistry and HPV-DNA (by polymerase chain reaction [PCR] and in situ hybridization [ISH]) using validated protocols on samples from 801 patients with head and neck cancer recruited prospectively between 2006 and 2011 in 4 randomized controlled trials (RCTs).
High-risk human papillomaviruses (HR-HPV), particularly types 16 and 18, have been found to play an important role in head and neck cancer, including oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). p16, a cell cycle inhibitor, has been postulated as a surrogate marker for HR-HPV, since p16 is aberrantly overexpressed in such lesions, especially in HR-HPV-positive OPSCC.
Large data on HPV DNA detection by PCR and p16 expression in HNC biopsies suggests that the probability of a cancer of the oral cavity, larynx, and hypopharynx being attributable to HPV is at least 5-fold lower than that for oropharyngeal cancer.
Analysis of 103 primary tumors has shown that increased nuclear p16 expression correlates with enhanced survival of head and neck cancer patients (p < 0.0000542), indicating the importance of nuclear p16 expression in prognosis.
Additionally, in the analysis of the studies following REMARK guidelines more rigorously, p16 hypermethylation had unfavorable impact on OS of NSCLC (HR 1.79, 95% CI: 1.35-2.39) and CRC (HR 1.96, 1.16-3.34), and on DFS of NSCLC (HR 2.12, 95% CI: 1.21-3.72) and head and neck cancer (HR 2.24, 95% CI: 1.35-3.73).
Comparison of human papillomavirus in situ hybridization and p16 immunohistochemistry in the detection of human papillomavirus-associated head and neck cancer based on a prospective clinical experience.
From this study, we identify minichromosome maintenance protein 7 (MCM7) and p16 as potentially useful biomarkers for HPV-positive head and neck cancer.
Detection of cyclin D1 amplification and p16 deletion using a simple and sensitive method will be valuable for the development of effective treatment modalities for head and neck cancer.
Our data indicate that p16 point mutations in HNC are less frequent, but inactivation by methylation of the promoter region could be involved in genesis and progression of HNC.