p16 and p53 expression status in head and neck squamous cell carcinoma: a correlation with histological, histoprognostic and clinical parameters

doi:10.1016/j.pathol.2016.01.005

Pathology

Volume 48, Issue 4, June 2016, Pages 341-348

https://doi.org/10.1016/j.pathol.2016.01.005 Get rights and content

Summary

Different histopathology and prognosis characterise the human papillomavirus (HPV)-related oropharyngeal tumours, but squamous cell carcinomas (SCC) of other localisations have not been exhaustively studied.

Tissues from 120 patients with a head and neck SCC were studied for the expression of p16 and p53, and the Brandwein–Gensler (BG) histological risk assessment model.

p16 positivity and p53 normal expression were significantly correlated with non-smoking, an earlier T stage and a non-keratinising morphology. The BG risk score was not associated with p16 or p53 expression; p16 expression was associated with a lymphocytic T-cytotoxic response. BG risk score was significantly correlated with overall survival and progression-free survival, while neither p16 nor p53 expression were associated with prognosis.

p16 and p53 expression are associated with the histological subtype and the T stage even in non-oropharyngeal-restricted tumours. The BG risk score is not correlated with p16 or p53 and retains its power in non-site-specific SCCs.

Introduction

Squamous cell carcinoma of the head and neck (SCCHN), involving the oral cavity, the nose/paranasal sinuses, the pharynx (naso-, oro- and hypopharynx) and the larynx has been traditionally attributed to tobacco exposure and alcohol abuse until 2000, when evidence began to mount regarding the role of human papillomavirus (HPV) in SCCHN pathogenesis and mostly in oropharyngeal cancer.¹

HPV-related SCCHN is a distinct tumour not sufficiently staged by the TNM staging system.² HPV16 and HPV18 are the two types largely involved, with the proportion of high-risk HPV positive cancers increasing in recent years.3, 4 It has been reported that 25.9% of SCCHN harbour an HPV infection, a number rising to 63.8% in the oropharyngeal group of SCC.⁵ In France, HPV infection is found in 46.5% of oropharyngeal and 10.5% of oral SCC.⁶ The importance of diagnosing an HPV-related SCCHN lies in its improved outcome, and the College of American Pathologists recommends routine HPV testing of the operated oropharyngeal SCC, while the National Comprehensive Cancer Network recommend the use of immunohistochemical p16 study in oropharyngeal SCC for prognostic purposes.⁷ Systematic research of HPV, however, is not actually recommended by the French Society of Otorhinolaryngology.⁶ At the same time, while the survival benefit is known for oropharyngeal cancer,⁵ studies in other sites report various results.

Mutation in the TP53 tumour suppressor gene is one of the earliest and more frequently detectable genetic alterations in SCCHN.⁸ The immunohistochemical expression of p53 is often used in daily practice as an additional aid in favour of a dysplasia or an invasive tumour, as its overexpression is compatible with an abnormal p53 gene status. However, studies correlating p53 expression with p16 expression and prognosis show variable results.

Despite repeated reports on the histopathological features of p16 positive oropharyngeal carcinomas, no similar investigations have been performed for non-oropharyngeal sites, or for p53 expression. Furthermore, there is no study assessing the histological parameters of prognosis in relation to these two prognostic/pathogenetic factors, p16 or p53.

The aim of this study was to investigate recently diagnosed SCCHN with representatives of all sites in order to better define the prognostic role of p16 and p53 and to investigate these parameters in comparison to a newly proposed system of histoprognostic evaluation.

Section snippets

Study population

A total of 120 patients diagnosed with a SCCHN were included in this study. Inclusion criteria were: (1) a recent diagnosis, less than 8 years, in order to have a homogenous treatment protocol and lifestyle habits, (2) acquisition of informed consent, (3) a histological diagnosis of squamous cell carcinoma of the conventional type, excluding cases of spindle cell, verrucous, adenosquamous, basaloid, papillary and undifferentiated SCC, (4) available surgically resected tumour tissue or

Patients' characteristics

Demographic data are presented in Table 1. Most patients were male, smokers, with a median age of 58.5 years at diagnosis. Larynx, oropharynx and hypopharynx were the main sites of involvement. Most cases were diagnosed at stage III and IV. Median follow up was 24 months. Sixty-seven patients died of the disease, 50 were alive; for three patients this information was not available as they were lost after the last follow-up. The 5-year survival rate was 40%. Sixty-one patients showed recurrence,

Discussion

The current study uses a relatively large and recently diagnosed cohort of head and neck SCCs in order to investigate the histological characteristics and the prognostic factors in the era of HPV related SCCHN. We show here that the Brandwein–Gensler (BG) histological risk assessment model retains its power in a non-site specific group of SCCHN and that although this model is not associated with p16 and p53 status of the tumour, its assessment of lymphocytic host response correlates well with

Conflicts of interest and sources of funding

The authors state that there are no conflicts of interest to disclose.

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Anatomical pathologyp16 and p53 expression status in head and neck squamous cell carcinoma: a correlation with histological, histoprognostic and clinical parameters

Summary

Introduction

Section snippets

Study population

Patients' characteristics

Discussion

Conflicts of interest and sources of funding

Semin Diagn Pathol

Eur Ann Otorhinolaryngol Head Neck Dis

Mod Pathol

Mod Pathol

Hum Pathol

Staging and treatment of oropharyngeal cancer in the human papillomavirus era

Head Neck

Prevalence and prognostic value of human papillomavirus genotypes in tonsillar squamous cell carcinoma: a Korean multicenter study

Cancer

Rising prevalence of human papillomavirus-related oropharyngeal cancer in australia over the last 2 decades

Head Neck

Human papillomavirus and survival of patients with oropharyngeal cancer

N Engl J Med

Head and neck cancers

J Natl Compr Canc Netw

Clinical update on cancer: Molecular oncology of head and neck cancer

Cell Death Dis

HPV-related nonkeratinizing squamous cell carcinoma of the oropharynx: utility of microscopic features in predicting patient outcome

Head Neck Pathol

Anatomical pathology
p16 and p53 expression status in head and neck squamous cell carcinoma: a correlation with histological, histoprognostic and clinical parameters