Complex Etiology Underlies Risk and Survival in Head and Neck Cancer Human Papillomavirus, Tobacco, and Alcohol: A Case for Multifactor Disease

Department of Epidemiology, College of Public Health, The University of Iowa, Iowa City, IA 52242, USA.
Journal of Oncology 01/2012; 2012(23):571862. DOI: 10.1155/2012/571862
Source: PubMed


Findings are inconsistent about whether tobacco, alcohol, and human papillomavirus (HPV) are two independent HNC risk factor groups that distinguish an infection-associated cancer from a tobacco/alcohol-associated HNC. We found that cancer in the oral cavity risk was greater in HPV-E6/E7 seropositive/heavy tobacco users (adjusted OR = 3.5) than in HPV-seronegative/heavy tobacco users (adjusted OR = 1.4); and HPV-seropositive/heavy alcohol users (adjusted OR = 9.8) had greater risk than HPV-seronegative/heavy alcohol users (adjusted OR = 3.1). In contrast, the risk of oropharyngeal cancer was greater in the HPV-seronegative/heavy tobacco (adjusted OR = 11.0) than in HPV-seropositive/heavy tobacco (adjusted OR = 4.7) users and greater in HPV-seronegative/heavy alcohol users (adjusted OR = 24.3) compared to HPV-seropositive/heavy alcohol users (adjusted OR = 8.5). Disease-specific and recurrence-free adjusted survival were significantly worse in oropharyngeal HPV-seronegative cases with no survival differences by HPV status seen in oral cavity cases. The association between tobacco/alcohol, HPV, and tumor site is complex. There appear to be distinct tumor site differences in the combined exposure risks, suggesting that different molecular pathways are involved.

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Available from: Linda M Rubenstein, Jul 08, 2014
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    • "Human papillomaviruses are now, together with smoking and alcohol consumption, an established risk factor for head and neck cancer [48]. HPVs are present in 67.0% of oropharyngeal cancers, especially tonsillar carcinomas. "
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    ABSTRACT: Background: Human papillomaviruses (HPVs) have been proved as one of the etiological factors of oropharyngeal squamous cell carcinoma (OPSCC). Patients with tumors of viral etiology have a lower recurrence rate and better prognosis. OPSCC is linked to an alteration in the immune system. Only a limited number of studies have correlated both the immunological parameters and HPV status with patient prognosis. The aim of this study was to determine whether HPV infection and the immunological status influence patient prognosis individually or in concurrence. Material and methods: Sixty patients with oral and oropharyngeal carcinomas were enrolled. They were divided into HPV-positive and HPV-negative groups based on the expression of HPV 16 E6 mRNA. Basic lymphocyte subpopulations were determined in the peripheral blood by means of flow cytometry. Results: Significantly better disease-specific survival (DSS) was observed in patients with HPV-positive tumors. Nodal status, tumor grade, recurrence, and CD8+/Tregs ratio were identified as factors influencing DSS. A higher level of Tregs and a lower ratio of CD8/Tregs influenced overall survival (OS) independently of HPV status and age. Patients with HPV-positive tumors and high levels of Tregs survived significantly better than patients from the other groups. Conclusion: Better survival is associated with HPV positivity and elevated Tregs levels. Our data suggest that HPV infection and Tregs do not influence patient prognosis in concurrence.
    BioMed Research International 04/2014; 2014:303929. DOI:10.1155/2014/303929 · 2.71 Impact Factor
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    • "They also share some risk factors, though their relative importance depends on the type of upper GI cancer. Whereas the main risk factors for oral cavity and pharyngeal cancer are alcohol consumption, smoking and human papillomaviruses (HPVs), HPV-16 in particular [7,8], the accepted risk factors for oesophageal cancer include alcohol, smoking, obesity and gastro-oesophageal reflux [9], and those for gastric cancer are Helicobacter pylori (H. pylori) infection, diet and smoking [10]. "
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    ABSTRACT: Although oral cavity, pharyngeal, oesophageal and gastric cancers share some risk factors, no comparative analysis of mortality rate trends in these illnesses has been undertaken in Spain. This study aimed to evaluate the independent effects of age, death period and birth cohort on the mortality rates of these tumours. Specific and age-adjusted mortality rates by tumour and sex were analysed. Age-period-cohort log-linear models were fitted separately for each tumour and sex, and segmented regression models were used to detect changes in period- and cohort-effect curvatures. Among men, the period-effect curvatures for oral cavity/pharyngeal and oesophageal cancers displayed a mortality trend that rose until 1995 and then declined. Among women, oral cavity/pharyngeal cancer mortality increased throughout the study period whereas oesophageal cancer mortality decreased after 1970. Stomach cancer mortality decreased in both sexes from 1965 onwards. Lastly, the cohort-effect curvature showed a certain degree of similarity for all three tumours in both sexes, which was greater among oral cavity, pharyngeal and oesophageal cancers, with a change point in evidence, after which risk of death increased in cohorts born from the 1910-1920s onwards and decreased among the 1950-1960 cohorts and successive generations. This latter feature was likewise observed for stomach cancer. While the similarities of the cohort effects in oral cavity/pharyngeal, oesophageal and gastric tumours support the implication of shared risk factors, the more marked changes in cohort-effect curvature for oral cavity/pharyngeal and oesophageal cancer could be due to the greater influence of some risk factors in their aetiology, such as smoking and alcohol consumption. The increase in oral cavity/pharyngeal cancer mortality in women deserves further study.
    BMC Cancer 04/2014; 14(1):254. DOI:10.1186/1471-2407-14-254 · 3.36 Impact Factor
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    • "Head and neck cancers (HNC) which involve malignant neoplasms of the oral cavity, pharynx, and larynx, are the sixth most common cancers threatening human life worldwide [1]. To date, there are ample evidences indicating that HNC is a complex multifactorial disorder involving genetic factors, lifestyle, tobacco smoke, alcohol consuming, and environmental factors [2-6] and some low-penetrant genes have been identified as potential HNC susceptibility genes [7-9]. Among them, an important one is xeroderma pigmentosum group D(XPD) gene, which is located on chromosome 19q13.3. "
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    ABSTRACT: Whether the single nucleotide polymorphism (SNP) Lys751Gln of xeroderma pigmentosum group D(XPD) gene increases susceptibility to head and neck cancer (HNC) is controversial and undetermined. Therefore, we conducted this meta-analysis to systematically assess the possible association between them. The OVID, Medline, Embase, Pubmed, Web of Science databases were searched to identify the eligible studies. The odds ratio (OR) with 95% confidence interval (95%CI) were used to assess the strength of association. A total of 11,443 subjects from eighteen studies were subjected to meta-analysis. Overall, XPD Lys751Gln polymorphism had no association with increased HNC risk under all five genetic models (P > 0.05). In the subgroup analysis by ethnicity and source of controls, still no significant association was found under five genetic models (P > 0.05). In the subgroup analysis by cancer type, XPD Lys751Gln polymorphism had statistically significant association with elevated laryngeal cancer (LC) and nasopharyngeal cancer (NPC) risk under heterozygous comparison and dominant model (P<0.05) and borderline significantly increased risk was found under allele contrast for LC and NPC. Carriers of Lys allele and Lys/Lys genotype may be associated with elevated LC and NPC risk. There is overall lack of association between XPD Lys751Gln polymorphism and HNC risk under all five genetic models and still no significant association was found in the subgroup analysis by ethnicity and source of controls. However, XPD Lys751Gln polymorphism was significantly associated with susceptibility to LC and NPC and the Lys allele and Lys/Lys genotype of XPD Lys751Gln polymorphism may be a risk factor for LC and NPC. However, relatively modest sample sizes were included in this meta-analysis and studies with large sample sizes and representative population are warranted to further clarify this finding.Virtual slides: The virtual slide(s) for this article can be found here:
    Diagnostic Pathology 01/2014; 9(1):15. DOI:10.1186/1746-1596-9-15 · 2.60 Impact Factor
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