Elsevier

Vaccine

Volume 30, Supplement 5, 20 November 2012, Pages F34-F54
Vaccine

Review
Human Papillomavirus and Diseases of the Upper Airway: Head and Neck Cancer and Respiratory Papillomatosis

https://doi.org/10.1016/j.vaccine.2012.05.070Get rights and content

Abstract

Human papillomavirus (HPV) infection is causally associated with benign and malignant diseases of the upper airway, including respiratory papillomatosis and oropharyngeal cancer. Low-risk HPV types 6 and 11 are the predominant cause of papillomatosis, whereas only HPV16 definitively satisfies both molecular and epidemiological causal criteria as a carcinogenic or high-risk type in the upper airway. HPV16 E6/E7 mRNA expression and integration are observed predominantly among oropharyngeal cancers, and experimental models have shown E6/E7 expression to be necessary for the initiation and maintenance of the malignant phenotype of these cancers. From an epidemiological perspective, a strong and consistent association between markers of HPV16 exposure and oropharyngeal cancer has been demonstrated in numerous case-control studies. HPV-positive oropharyngeal cancers have also been shown to be distinct from HPV-negative head and neck squamous cell cancers with regard to risk-factor profiles, molecular genetic alterations, population-level incidence trends over time, and prognosis. Tumor HPV status (as determined by certain HPV16 in situ hybridization assays or certain p16 immunohistochemistry assays) is the strongest determinant of survival for patients with local-regionally advanced oropharyngeal cancer: patients with HPV-positive cancer have at least a 50% improvement in overall survival at 5 years, which is equivalent to an approximate 30% difference in absolute survival. Thus, HPV status determination is now part of the routine diagnostic evaluation for prognostication. Preliminary evidence indicates that a small proportion of head and neck cancers may be caused by additional HPV types (e.g., 18, 31, 33, 35) and that HPV-caused cancers may rarely arise from non-oropharyngeal sites (e.g., the oral cavity, nasopharynx, and larynx). Whether or not HPV vaccination has the potential to prevent oral HPV infections that lead to cancer or papillomatosis in the upper airway is currently unknown, as is the potential for secondary prevention with HPV detection.

This article forms part of a special supplement entitled “Comprehensive Control of HPV Infections and Related Diseases” Vaccine Volume 30, Supplement 5, 2012.

Highlights

► HPV16 is necessary for initiation/malignant phenotype of some oropharynx cancers. ► Infection by HPV16 is associated with elevated odds of oropharynx cancer. ► Tumor HPV status is an important prognostic factor for oropharynx cancer. ► HPV-positive oropharynx cancer incidence is increasing in developed countries. ► Respiratory papillomatosis is caused by peripartum/sexual transmission of HPV6/11.

Section snippets

Causal criteria for an etiological association

The Cancer Etiology Branch of the United States National Cancer Institute has formulated criteria to guide establishment of a causal relationship between a carcinogen and the development of a specific cancer type [1]. These criteria are similar to those proposed by zur Hausen H [2] to establish involvement of an infectious agent, and include molecular-pathological, experimental and epidemiological evidence. For epidemiological evidence, the criteria originally established by AB Hill provide a

Trends in incidence for head and neck cancer

Head and neck cancer incidence displays geographic and temporal heterogeneity, and has been historically correlated with patterns of tobacco use [79]. Regions of high head and neck cancer incidence include countries in Asia, where prevalence of chewing tobacco (and other products such as betel leaf/paan and areca nut) is high, as well as parts of central and Eastern Europe, and South America [79], [80]. Despite overall declines in head and neck cancer incidence in most parts of the world,

Clinical significance of HPV in head and neck cancers

The presence of HPV in HNSCC has recently become of clinical importance for reasons related to both diagnostics and prognostication.

Respiratory papillomas

Recurrent respiratory papillomatosis (RRP) is caused primarily by HPVs 6 and 11, with a small fraction (less than 5%) caused by HPV16 or other types [130]. The disease is characterized by growth of multiple papillomas, usually arising from the larynx.

RRP can manifest in early childhood (juvenile onset) or in adulthood and is a rare disorder, with an estimated incidence of approximately 3 per 1 million person-years in children, and a prevalence of 3 to 7 per 100,000 for both pediatric and adult

Primary and secondary prevention of HPV-associated diseases of the upper airway

The potential for clinical intervention into the natural history of HPV-positive oropharyngeal cancer is unknown at this time. While HPV vaccines have been shown to prevent incident and persistent anogenital infection, as well as anogenital precancers associated with HPV16 and 18, vaccine efficacy in preventing oral HPV infections has not been investigated. Observed associations between sexual behavior and both oropharyngeal cancer and adult onset respiratory papillomatosis suggest that

Acknowledgements

The work was partially supported by public grants from the European Commission (7th Framework Programme grants HEALTH-F3-2010-242061, PREHDICT and HEALTH-F2-2011-282562, HPV AHEAD), from the Instituto de Salud Carlos III (Spanish Government) (grants FIS FIS PI10/02995, FIS PI08/1535, FIS PI11/02096, FIS PI11/02104, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095 and CIBERESP) and from the Agència de Gestió d’Ajuts Universitaris i de Recerca – Generalitat de Catalunya (Catalonian Government)

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