Table 3.

Summary of studies to define buccal cell changes associated with clinicopathologic observations of patients with oral cancer

No.First author (year) (ref.)Clinical correlate*,
1Mager (2005) (87)Bacteria countsYesEvaluation of salivary bacteria counts of oral bacteria in individuals with cancerous lesions (n = 229) versus healthy controls (n = 45). Of 40 common oral bacteria, significantly higher counts (P < 0.0001) were observed for Capnocytophaga gingivalis, Prevotella melaninogenica, and Streptococcus mitis. When tested as diagnostic markers, the three species were found to predict 80% of cancers (sensitivity). The authors concluded that salivary counts of certain bacteria may be diagnostic indications of oral squamous cell carcinoma.
2Maraki (2004) (90)Cytology and DNAYesA study of 98 patients with clinically suspicious oral lesions was undertaken to evaluate the diagnostic accuracy of exfoliative cytology and DNA image cytometry for the very early diagnosis of oral cancer. Brushings and scalpel biopsies were obtained from 98 patients with suspicious oral lesions. The authors concluded that cytology with DNA image cytometry is a highly sensitive, specific, and noninvasive method for the early diagnosis of oral epithelial neoplasia.
3Cheng (2004) (89)Terminal deoxynucleotidyl transferase–mediated dUTP nick end labelingYesApoptotic cells in whole saliva were detected in four groups of study subjects using the terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling assay. The apoptotic cells showed morphology similar to normal exfoliated epithelial (buccal) cells of oral mucosa. The fraction of apoptotic cells in treated malignant patients was significantly higher (P < 0.05) than that of healthy volunteers, premalignant patients, and untreated malignant patients.
4Lopez (2004) (88)p53YesA study of 34 patients with leukoplakia was undertaken to assess the merit of using cytologic specimens for defining p53 gene alteration in oral squamous cell carcinoma risk patients. Using an oral rinse and brush swabbing method to collect buccal cells, 11 mutations in the p53 gene were detected in the oral cytologic specimens. The authors concluded that the noninvasive method may be useful in the follow-up of at-risk patients and introduces new possibilities to analyze molecular markers before malignant lesions are clinically apparent.
5Ramirez (2002) (91)MicronucleiYesThe micronucleus test was used as an indicator of genotoxic exposition and clastogenic action of alcohol because it is associated with chromosome aberrations and is related to the development of oral cancer. In this study of buccal cells of 30 alcoholics with carcinomas, the frequency of micronuclei was 7-fold, highly significant (P = 0.0005) for regions around the lesions. A 3-fold increase was observed for the opposite nonmalignant region, and no difference was found for upper gingival-labile gutter.
6Casartelli (2000) (92)MicronucleiYesEvaluation of micronuclei of buccal cells of different areas of the patients. When compared with healthy tissue, the study documented a significant increase in micronuclei of preneoplastic lesions (n = 47) and for carcinomas (n = 21). With all samples, micronucleus frequencies were systematically higher when cells were collected by vigorous rather than light scrapings, suggesting a decreasing gradient from basal to superficial layers of mucosa. The micronuclei frequency did not vary with the sex or age of patients, although it did vary with the anatomic site of the lesions. The observed gradual increase in micronuclei counts from normal mucosa to precancerous lesions suggests a link of this biomarker with neoplastic progression.
7van Oijen (1998) (93)Cell proliferationYesA study was undertaken to assess the number of proliferating cells in the oral epithelium (buccal mucosa) from smokers and ex-smokers. The proliferation index was assessed by an indirect assay for the proliferation biomarker Ki-67. The epithelium from both smoking cancer patients and health smoking individuals showed an increase in cell proliferation compared with epithelia from nonsmoking subjects (P < 0.001). Further, ex-smokers in both groups showed a trend toward increased cell proliferation. Increased cell proliferation after cessation of smoking would indicate permanent epithelial alterations. Ex-smokers also showed a greater proliferation index than nonsmokers, which showed that permanent changes had occurred.
8Babu (1996) (94)Cytology and cell proliferationYesA prospective study examined the in vivo effects of pan masala/gudakhu and betel quid chewing on buccal mucosal cytology in 50 patients with oral submucous fibrosis and 40 controls. The study found a significantly higher (P < 0.05) percentage of nucleolated intermediate cells or a proliferative fraction of buccal mucosa cells was significantly higher in all habitual chewers than in controls.
9Benner (1994) (52)MicronucleiYesStudied buccal cell micronuclei frequency of specimens from both visible lesions and normal-appearing mucosa (P < 0.01; n = 24 subjects).
  • * Buccal cell changes were evaluated using the micronuclei assay and other tests.

  • Statistically significant association identified between buccal cell changes and tobacco smoking: positive (yes) or negative (no) association.