Background: High-risk human papillomaviruses (HPVs) are etiologic agents for anogenital tract cancers and have been detected in head and neck squamous cell carcinomas (HNSCCs). We investigated, retrospectively, an etiologic role for HPVs in a large series of patients with HNSCC. Methods: Tumor tissues from 253 patients with newly diagnosed or recurrent HNSCC were tested for the presence of HPV genome by use of polymerase chain reaction (PCR)-based assays, Southern blot hybridization, and in situ hybridization. The viral E6 coding region was sequenced to confirm the presence of tumor-specific viral isolates. Exons 5‐9 of the TP53 gene were sequenced from 166 specimens. The hazard of death from HNSCC in patients with and without HPVpositive tumors was determined by proportional hazards regression analysis. Results: HPV was detected in 62 (25%) of 253 cases (95% confidence interval [CI] = 19%‐30%). Highrisk, tumorigenic type HPV16 was identified in 90% of the HPV-positive tumors. HPV16 was localized specifically by in situ hybridization within the nuclei of cancer cells in preinvasive, invasive, and lymph node disease. Southern blot hybridization patterns were consistent with viral integration. Poor tumor grade (odds ratio [OR] = 2.4; 95% CI = 1.2‐ 4.9) and oropharyngeal site (OR = 6.2; 95% CI = 3.1‐12.1) independently increased the probability of HPV presence. As compared with HPV-negative oropharyngeal cancers, HPVpositive oropharyngeal cancers were less likely to occur among moderate to heavy drinkers (OR = 0.17; 95% CI = 0.05‐0.61) and smokers (OR = 0.16; 95% CI = 0.02‐1.4), had a characteristic basaloid morphology (OR = 18.7; 95% CI = 2.1‐167), were less likely to have TP53 mutations (OR = 0.06; 95% CI = 0.01‐0.36), and had improved disease-specific survival (hazard ratio [HR] = 0.26; 95% CI = 0.07‐0.98). After adjustment for the presence of lymph node disease (HR = 2.3; 95% CI = 1.4‐ 3.8), heavy alcohol consumption (HR = 2.6; 95% CI = 1.4‐4.7), and age greater than 60 years old (HR = 1.4; 95% CI = 0.8‐2.3), all patients with HPV-positive tumors had a 59% reduction in risk of death from cancer when compared with HPV-negative HNSCC patients (HR = 0.41; 95% CI = 0.20‐0.88). Conclusions: These data extend recent molecular and epidemiologic studies and strongly suggest that HPV-positive oropharyngeal cancers comprise a distinct molecular, clinical, and pathologic disease entity that is likely causally associated with HPV infection and that has a markedly improved prognosis. [J Natl Cancer Inst 2000; 92:709‐20]

Evidence for a Causal Association Between Human Papillomavirus and a Subset of Head and Neck Cancers

In the United States, cancers of the oral cavity and oropharynx represent approximately three percent of all malignancies in men and two percent of all malignancies in women. The American Cancer Society estimates that 28,900 new cases of oral cancer will be diagnosed in 2002, and nearly 7,400 people will die from this disease. Over 90 percent of these tumors are squamous cell carcinomas, which arise from the oral mucosal lining. In spite of the ready accessibility of the oral cavity to direct examination, these malignancies still are often not detected until a late stage, and the survival rate for oral cancer has remained essentially unchanged over the past three decades. The purpose of this article is to review the clinical features of oral cancer and premalignant oral lesions, with an emphasis on early detection.

/pdf/oral-cancer-and-precancerous-lesions-1ae8yh9kz7.pdf

Oral cancer and precancerous lesions.

It has been estimated by various authorities that about one-third of cancers in Western high-income societies are attributable to factors relating to food, nutrition and physical activity. Identifying with confidence specific associations between dietary patterns, foods, body composition or individual nutrients is not simple because of the long latent period for cancer development, its complex pathogenesis and the challenge of characterising the multidimensional aspects of diet and activity over a lifetime. Reliable conclusions must therefore be drawn not only from randomised controlled trials but from a variety of methodological approaches, judged within a classic framework for inferring causality. Using a newly-developed method with a protocol for standardising the literature search and for analysis and display of the evidence, nine independent academic centres have conducted systematic reviews addressing the causal associations between food, nutrition and physical activity and risk of development of seventeen cancers, as well as of weight gain and obesity. A review has also examined the efficacy of such interventions in subjects with cancer. The reviews have been assessed by an independent Panel of twenty-one international experts who drew conclusions with grades of confidence in the causality of associations and made recommendations. Recommendations are given as public health goals as well as for individuals.

/pdf/the-second-world-cancer-research-fund-american-institute-for-4wjy2ptzze.pdf

The second World Cancer Research Fund/American Institute for Cancer Research expert report. Food, nutrition, physical activity, and the prevention of cancer: a global perspective.

Background Although epidemiologic studies have long associated tobacco and alcohol use with the development of squamous-cell carcinoma of the head and neck, the molecular targets of these carcinogens have yet to be identified. We performed a molecular analysis to determine the pattern of mutations in the p53 gene in neoplasms from patients with squamous-cell carcinoma of the head and neck and a history of tobacco or alcohol use. Methods Sequence analysis of the conserved regions of the p53 gene was performed in tumor samples from 129 patients with primary squamous-cell carcinoma of the head and neck. We then used statistical analysis to identify any patient characteristics associated with mutation of the p53 gene. Results We found p53 mutations in 42 percent of the patients (54 of 129). Fifty-eight percent of the patients who smoked cigarettes and used alcohol (37 of 64; 95 percent confidence interval, 45 to 70 percent), 33 percent of the patients who smoked but abstained from alcohol (13 of 39; 95 percen...

https://www.nejm.org/doi/pdf/10.1056/NEJM199503163321104

Association between Cigarette Smoking and Mutation of the p53 Gene in Squamous-Cell Carcinoma of the Head and Neck

Summary Use of smokeless tobacco products is common worldwide, with increasing consumption in many countries. Although epidemiological data from the USA and Asia show a raised risk of oral cancer (overall relative risk 2·6 [95% CI 1·3–5·2]), these are not confirmed in northern European studies (1·0 [0·7–1·3]). Risks of oesophageal cancer (1·6 [1·1–2·3]) and pancreatic cancer (1·6 [1·1–2·2]) have also increased, as shown in northern European studies. Results on lung cancer have been inconsistent, with northern European studies suggesting no excess risk. In India and Sudan, more than 50% of oral cancers are attributable to smokeless tobacco products used in those countries, as are about 4% of oral cancers in US men and 20% of oesophageal and pancreatic cancers in Swedish men. Smokeless tobacco products are a major source of carcinogenic nitrosamines; biomarkers of exposure have been developed to quantify exposure as a framework for a carcinogenesis model in people. Animal carcinogenicity studies strongly support clinical results. Cancer risk of smokeless tobacco users is probably lower than that of smokers, but higher than that of non-tobacco users.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(08)70173-6.pdf

Smokeless tobacco and cancer

Background. Independent carcinogenic effects of alcohol drinking and tobacco smoking as well as their interaction can be usefully studied in a population of heavy drinkers and smokers.



Methods. A hospital-based case-control study was conducted during 1972 to 1983 in a large Veterans hospital in East Orange, New Jersey. A total of 359 oral cavity-oropharynx cancer cases and 2280 controls were interviewed according to tobacco smoking, use of smokeless tobacco, alcoholic beverage, coffee and tea drinking, race, family origin, religion, and occupation as bartender.



Results. Odds ratio of oral cancer increased up to the level of 35 cigarettes per day and 21 whiskey equivalents per day: no further increase was found for higher level of exposure to either factor. A protective effect of quitting smoking was found, but the number of former smokers was small. No difference occurred in oral cancer risk according to type of alcoholic beverage drunk. An interaction effect compatible with a multiplicative model was found between the two exposures. Blacks were at lower risk than whites, and, in the latter group, individuals of Italian origin were at lower risk than individuals from northern or central European countries.



Conclusions. Alcohol drinking and tobacco smoking were responsible for the majority of oral cancer cases in this population of US Veterans.

Arthur Mashberg

Papers

Tobacco smoking, alcohol drinking, and cancer of the oral cavity and oropharynx among U.S. veterans.