International Journal of Radiation Oncology*Biology*Physics
Biology ContributionHuman Papillomavirus (HPV) Infection in Squamous Cell Carcinomas Arising From the Oropharynx: Detection of HPV DNA and p16 Immunohistochemistry as Diagnostic and Prognostic Indicators—A Pilot Study
Introduction
More than 50,000 cases of head and neck cancer, predominantly squamous cell carcinomas (HNSCC), occurred in the United States in 2012, resulting in approximately 13,000 deaths (1). HNSCC grossly accounts for 3.5% of all malignant tumors in the United States (1) and is more prevalent in other parts of the world, such as India, Southeast Asia, and Brazil (2). Well-established risk factors for the development of HNSCC include cigarette smoking and alcohol abuse 3, 4. Another emerging risk factor for oropharyngeal SCC (OPSCC) is infection with high-risk (HR) human papillomavirus (HPV) 5, 6, the role of which, in carcinogenesis of the uterine cervix, has been extensively studied (4), although its relevance for carcinogenesis in other head and neck sites (if any) remains unclear 5, 6, 7. The emergence of HR HPV infection underlies a marked increase in the incidence of OPSCC 8, 9, particularly in young patients (10). A general decrease in the incidence of SCC in other head and neck mucosal sites has been observed in Western countries because of successful campaigns for primary prevention, particularly against cigarette smoke 1, 11.
The significance of HPV infection in nonoropharyngeal head and neck sites might previously have been overestimated 12, 13 because of the use of p16 expression as a diagnostic tool, based on a uterine cervix model 14, 15. Importantly, we recently demonstrated that p16 immunohistochemistry (IHC) is unreliable for diagnosing HPV infections of head and neck sites outside the oropharynx (6). The primary aim of this study was to evaluate, on formalin-fixed paraffin-embedded (FFPE) samples, which are by far the most easily available in daily clinical practice, the reliability of p16 IHC and of HPV-DNA detection in the diagnosis of HPV infection in OPSCC, and their clinical and prognostic rsignificance.
Section snippets
Patient characteristics
Patients with oropharyngeal neoplasms are evaluated at the same institution by a multidisciplinary head and neck tumor board, which provides therapeutic recommendations following histological diagnosis and staging according to TNM classification (16). Samples were collected from 50 patients affected by primary, previously untreated, advanced oropharyngeal SCC between March 2009 and December 2011. The patients were enrolled in the study, which had previously been approved by the ethical
Results
Patient and tumor characteristics are shown in Table 1. All patients enrolled in this study were available for follow-up.
The most frequent subsite from which the SCCs originated was the tonsil (68%), followed by the base of the tongue (22%). We observed a marked prevalence of stage IV cases (76%). More than 85% of the patients in our study cohort presented with clinically positive lymph nodes at diagnosis.
The specific genotype of HPV was evaluated in fresh samples and consistently found to be
Discussion
The results of this study confirm the relevance of HPV infection as a risk factor for OPSCC 5, 6, 22. The infection rate in this group of patients is consistent with previous reports on OPSCC from Europe 23, 24, 25, which generally estimate the HR HPV prevalence between 25% and 50%, also taking account of the markedly reduced prevalence in southern Europe over that in other areas such as Scandinavia (26). Nevertheless, the prevalence of disease in this cohort was lower than that observed in our
References (37)
- et al.
Clinically significant human papilloma virus in squamous cell carcinoma of the head and neck in UK practice
Clin Oncol (R Coll Radiol)
(2012) - et al.
The influence of HPV-associated p16-expression on accelerated fractionated radiotherapy in head and neck cancer: Evaluation of the randomised DAHANCA 6&7 trial
Radiother Oncol
(2011) - et al.
A review of human carcinogens—part B: Biological agents
Lancet Oncol
(2009) - et al.
A comparison of clinically utilized human papillomavirus detection methods in head and neck cancer
Mod Pathol
(2011) HPV and prognosis for patients with oropharynx cancer
Eur J Cancer
(2009)- et al.
Molecular markers in laryngeal squamous cell carcinoma: Towards an integrated clinicobiological approach
Eur J Cancer
(2005) - et al.
Human papilloma virus in head and neck cancer: The need for a standardised assay to assess the full clinical importance
Eur J Cancer
(2009) - et al.
Cancer statistics, 2013
CA Cancer J Clin
(2013) - et al.
Treatment of cancer of the head and neck
CA Cancer J Clin
(1995) - et al.
Head and neck surgery and oncology
(2003)
Rosenberg's cancer: Principles & practice of oncology
Evidence for a causal association between human papillomavirus and a subset of head and neck cancers
J Natl Cancer Inst
HPV infection in squamous cell carcinomas arising from different mucosal sites of the head and neck region. Is p16 immunohistochemistry a reliable surrogate marker?
Br J Cancer
The mutational landscape of head and neck squamous cell carcinoma
Science
Human papillomavirus and rising oropharyngeal cancer incidence in the United States
J Clin Oncol
Human papillomavirus as a risk factor for the increase in incidence of tonsillar cancer
Int J Cancer
Trends in head and neck cancer incidence in relation to smoking prevalence: An emerging epidemic of human papillomavirus-associated cancers?
Cancer
Trends in incidence and prognosis for head and neck cancer in the United States: A site-specific analysis of the SEER database
Int J Cancer
Cited by (0)
This study was funded exclusively by research grant D1.1 from the Università Cattolica del Sacro Cuore awarded in 2010 to professor Giovanni Delogu.
Conflict of interest: none.