Head and neck (H&N) cancer usually includes malignant ... Oropharynx and oral cavity squamous cell cancer ... association between HPV positive tumours.
Changing Epidemiology of Head and Neck Cancer ead and neck (H&N) cancer usually includes malignant tumours arising from the mucosa of the upper aerodigestive tract (UADT) from nasopharynx to larynx / trachea, while paranasal sinuses, nose, salivary glands, thyroid, parathyroid glands and cervical oesophagus are less frequently listed within this classification. In this report, all sites are considered for completeness. Malignant tumors arising from central and peripheral nervous system, mesenchymal (muscle and blood vessels), haematopoetic tissue (leukaemia and lymphoma) and skin are generally excluded from this definition. Little data is available on H&N cancer epidemiology, most are derived from the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) programme of the United States (US) registers, with lesser data coming from the cancer registers of the European countries. About 75,000 new cases of H&N cancer per year were recorded in the US in 2001, with approximately 30,000 associated deaths. According to the SEER data, between 1975 and 2001 the incidence for most H&N cancer sites has globally decreased except for tongue (up 16%), tonsil (12%), nose (12%), salivary glands (20%) and thyroid (up 52%). Between 1990 and 2001, the mortality has remained stable for thyroid, while it has fallen at all other sites. Little has changed over a similar time period with respect to histology. Between 1999 and 2001 at least 80% of diagnosed H&N cancers were squamous cell carcinomas, making it the main histologic type. Among salivary gland cancers (SGC), adenoid cystic carcinoma is the predominant histology in the submandibular gland; mucoepidermoid in the parotid gland and adenocarcinoma in the paranasal sinuses. Papillary is the main histologic type in thyroid cancer, all other histologies representing less than 3% of cases [1]. We have focused our attention in particular on sites for which an increased incidence has been recorded.
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Laura D Locati, Medical Oncologist with a special expertise in head and neck cancer. Fondazione IRCCS ‘Istituto Nazionale dei Tumori’ in Milan, Italy.
Paolo Bossi, Medical Oncologist with a special expertise in head and neck cancer. Fondazione IRCCS ‘Istituto Nazionale dei Tumori’ in Milan, Italy
Lisa Licitra Medical Oncologist, responsible of the medical treatment of head and neck cancer patients at Fondazione IRCCS ‘Istituto Nazionale dei Tumori’ in Milan, Italy.
Correspondence: Medical Oncology 3, Fondazione IRCCS- Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy. Email: lisa.licitra@ istitutotumori.mi.it
Oropharynx and oral cavity squamous cell cancer A slight increase in the incidence of tonsil and tongue cancer has emerged from SEER data, against a reduction of mortality. Over the last few years human papilloma virus (HPV) infection has been recognized to 8
have a pathogenetic role in approximately 25% of oropharynx carcinomas. Lingual and palatine tonsils are the most involved sites compared to the other H&N sites, the reason for this behaviour being still unknown. More than 120 different HPV types have been so far singled out and among the high risk oncogenic types such as HPV 16, 18, 31, 33, 35, HPV 16 is the most involved (90-95% of cases) in H&N squamous cell cancer. The method of transmission seems to be related to sex, in particular there is a strong association between HPV positive tumours and specific sexual behaviors, such as oral sex and oral-anal intercourse. If a relationship between oral HPV infection and genital HPV infection exists, it is still to be defined. This topic has been analyzed in a study including 172 women with human immunodeficiency virus (HIV) positive and 86 HIV negative women. Oral HPV infections seem to be less common than cervical HPV infections in both groups, oral HPV infections were more common in cases of concomitant cervical HPV infections and the presence of simultaneous oral and cervical infections by the same HPV types are rare, although the latter condition was present in more women than expected, making oral and cervical HPV infections two related entities [2]. Younger age, nonsmokers, nondrinkers, with the same risk of cancer development among both genders are the demographic characteristics of HPV positive tumors. Morphologically, a basaloid histology and a poorly differentiated grade are more frequently associated with HPV positive cancer. Molecularly, cancers containing integrated and transcriptionally active HPV16, generally carry a wild type TP53. Indeed TP53 is functionally inactivated by viral E6 oncoprotein and the same happens for pRb, which is inactivated by viral oncoprotein E7. These molecular features are completely different from those recorded in HPV negative tumors, where TP53 is often mutated due to carcinogens in tobacco smoke and amplification of cyclin D1. Besides, in HPV negative tumours, the inactivation of p16 alters the pRb pathway [3]. Probably due to the different pathogenetic origin, HPV positive cancer has a better prognosis, which along with reduction of risk of second tumour development [4], contributes to improve patient survival. In oral cavity cancer the evidence of pathogenic role of HPV is less evident. Volume 1 Issue 5 • February/March 2007
However, the incidence rate is higher for the tongue, while tonsil and nose cancer incidences are very similar, thus suggesting an exposure to the same risk factors. HPV infection seems to play a role in the pathogenesis of all these cancers. Laryngeal cancer (LC) According to the SEER data, incidence of LC decreased by 26% between 1975-2001, while five-year relative survival decreased from 68.1% (1980-1982) to 64.7% (1992-1999). These data were confirmed both by SEER and National Cancer Data Base (NCDB). Interestingly, there was a more apparent survival decline for advanced glottic cancer than for early stage, while the opposite happened for supraglottic lesions, including T3N0 cases for all subsites. The conservative non-surgical management of LC during these years has been claimed to be the main cause. However other factors, such as the less aggressive surgical approaches, such as endoscopic laryngeal resections, as well as neck management, could not be ruled out due to incomplete data. Moreover, a shift of LC during the same analysed period among minorities and lower income groups could have contributed to these disappointing results [5]. Fortunately this trend seems to have tipped over in the last few years (1999-2001), with a slight mortality decrease of 6% in US [6]. By contrast, from 1980 to 2001 a variable but steady mortality decrease has been recorded in Europe [7], which is probably due to the reduction of tobacco and alcohol consumption. Paranasal sinus cancer At sinus sites a significant decrease of mortality has been shown in SEER, probably due to the improvement in treatment management or changing tumour biology and risk factors. A possible role of HPV infection in pathogenesis of sinonasal carcinomas is a matter of debate. HPV DNA type 16 was present in at least 50% of nonkeratinising carcinomas, characterized also by immuno-staining of p16, high labeling score for Ki-67 and negative or low reactivity to p53 [8]. Besides, low risk HPV type 6 and 11 were also found in inverted papillomas [9], thus suggesting again a role for HPV infection in pathogenesis of both benign and malignant lesions of the head and neck. Thyroid cancer (TC) The increased incidence registered between 1973 and 2002 was mostly related to papillary carcinoma diagnosis, without any significant difference for the less frequent histotypes, such as follicular, medullary and anaplastic carcinoma. These data have been interpreted as the result of the increased number of detected small nodules (
