Smoking and drinking in relation to oral potentially malignant disorders in Puerto Rico: a case-control study

The clinical term "oral potentially malignant disorders" (OPMDs) is used to refer to a number of clinical presentations that carry an elevated risk of oral cancer [1]. In Puerto Rico, OPMDs most frequently present as leukoplakia and erythroplakia and are often diagnosed histopathologically as oral hyperkeratosis, epithelial hyperplasia, and epithelial dysplasia (OED). Oral hyperkeratosis presents histopathologically as a thickened keratotic layer on the epithelial surface, epithelial hyperplasia is characterized by a thickening of the spinous spinosum (acanthosis) and OED presents as alterations in cellular proliferation and maturation of the oral epithelium [1‐3]. Previous reports have documented the malignant potential of oral hyperkeratosis/epithelial hyperplasia and OED [4‐9].

It is well-established that tobacco smoking and alcohol consumption are important independent risk factors for squamous cell carcinoma of the oral cavity and pharynx [10, 11]. A number of studies in disparate areas around the world have also reported a positive association between smoking tobacco and the risk of both oral leukoplakia and OED [12]. Findings with regard to a link between alcohol consumption and OPMDs have been less consistent [12].

The purpose of the current analysis was to evaluate smoking and drinking as risk factors for OPMDs on the island of Puerto Rico where a high incidence of oral cancer is observed, particularly among males [13].

All individuals diagnosed with an OPMD or a benign oral tissue condition were identified by reviewing pathology reports generated via pathology laboratories located in cities around Puerto Rico. The study began with one participating laboratory in February 2003; additional laboratories were added over time to a total of six in October 2007 at the conclusion of subject identification. Persons with a histopathologic diagnosis of oral hyperkeratosis, epithelial hyperplasia, or OED were categorized as having an OPMD. Seven subjects diagnosed with lichen planus were excluded from the primary analysis given the controversy over its malignant potential [14], but those subjects were included as OPMD cases in a secondary analysis. Individuals histopathologically diagnosed with one or more of the following were classified as having a benign oral tissue condition: benign adenoma, amalgam tattoo, cyst, fibroma, fibrous histocytoma, granuloma, hemangioma, incontinentia pigmenti, inflammation, benign ulceration, lipoma, mucocele, mucositis, papilloma, Sjoegren syndrome, sialandenitis, or reactive, non-epithelial hyperplasia. When a subject was diagnosed with more than one eligible oral abnormality, s/he was classified as having the more severe disease condition, e.g., if a subject was diagnosed with both a benign oral tissue condition and OED, the disease status was classified as OED.

Subjects were included in the study if they were 30+ years of age at diagnosis, had no previous history of the diagnosed oral abnormality, could speak Spanish or English, and were able to provide reliable exposure information as judged by the trained interviewers.

After obtaining permission to contact an identified individual from his/her surgeon of record, each potential subject was contacted by study personnel, first via mail, and subsequently via telephone to answer any questions regarding participation and to schedule an in-person interview appointment. Two trained interviewers, who were blinded to both study hypotheses and disease status, used a standardized, structured questionnaire that included questions on smoking, drinking, and medical/dental history as well as information on demographics and dietary habits. Each subject received $20 reimbursement for their participation time.

Smoking tobacco use was defined in terms of cigarettes, pipes, and cigars. An "ever smoker" was defined as a person who self-reported smoking at least 100 cigarettes during the course of his/her lifetime or having smoked pipes or cigars for six months or more. A "current smoker" was defined as a person who self-reported smoking within the calendar year prior to the year of diagnosis while an "ex-smoker" was defined as an ever smoker who had quit smoking for more than one calendar year prior to the diagnosis year. For instance, a subject diagnosed in 2005 who quit smoking in 2004, would be classified as a current smoker; however, the same individual would be classified as an ex-smoker if s/he quit smoking in 2003. Cigarette equivalents were calculated based on the conversion factor of 1 cigarette = 1/2 pipe = 1/4 cigar and reported in terms of average cigarette equivalents per day [15]. Pack-year equivalents of smoking was calculated based upon the average number of pack-equivalents smoked per day times the number of smoking years.

Alcoholic beverage consumption was obtained in terms of beer, wine, and hard liquor. An "ever drinker" was defined as a person who self-reported consuming at least 12 drinks of any alcoholic beverage type over his/her lifetime. A "current drinker" was defined as a person who reported drinking any type of alcoholic beverage within the calendar year prior to the diagnosis year while an "ex-drinker" was defined as an ever drinker who had discontinued all drinking for more than one calendar year prior to the diagnosis year. The average number of drinks consumed per week was calculated based upon the reported number of 12-ounce beers, 4-ounce glasses of wine, and 1.5-ounce shots of hard liquor consumed per week [15‐17].

We employed standard statistical methods to evaluate differences in means and proportions. Odds ratios (ORs) and their 95% confidence intervals (95% CIs) were obtained using unconditional logistic regression [18]. Where indicated, ORs were adjusted for age (4 levels), gender, education (3 levels), daily fruit & vegetable intake (4 levels), and smoking (current vs. non-current) or drinking (4 levels). Levels of tobacco smoking (average cigarette equivalents/day, pack-year equivalents) were stratified into tertiles based upon consumption levels in the benign conditions group while the frequency of alcohol consumption was categorically defined as 0, > 0-< 7, 7-20, and > 20 drinks/wk. Crude and adjusted ORs were estimated by entering the applicable smoking and drinking terms, as factored variables, into the statistical models.

Tests of linear trend were conducted by adding the relevant ordinally-defined variable as a variate into the next lower order model and evaluating the statistical significance of that addition using the Wald statistic. An exploratory evaluation of the interaction between smoking and drinking was performed.

The study protocol was reviewed and approved by the Institutional Review Boards of the University of Puerto Rico Medical Sciences Campus and New York University.

A total of 241 subjects meeting the study eligibility criteria were included in the analysis. Table 1 presents the distribution of study participants by key variables of interest. The OPMD group (n = 86) was older than the benign group (n = 155) while the two groups were not significantly different in terms of gender, education, or fruit and vegetable intake.

Tobacco and alcohol consumption are well-recognized risk factors for cancers of the oral cavity and pharynx [12, 17, 19]. In Puerto Rico, it is estimated that 76% of oral and pharyngeal cancer cases among men and 52% among women are attributable to smoking and/or alcohol consumption [17]. Comparatively few epidemiologic studies, however, have investigated the role of tobacco and alcohol in relation to OPMD risk. In the current study, conducted in Puerto Rico, we evaluated smoking and drinking as risk factors for OPMDs.

We compared smoking and drinking patterns between individuals diagnosed with an oral potentially malignant disorder relative to persons diagnosed with a benign oral tissue condition. Our findings suggest that current smoking is a substantial risk factor for OPMDs while former smokers have a considerably reduced risk compared to current smokers. There was little evidence suggesting that alcohol consumption was positively associated with OPMD risk in Puerto Rico.