Cervical Neoplasia and Cigarette Smoking: Are They Linked?

, , , National Institute of Mental Health

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In This Article

Biologic Plausibility

Chemical carcinogens. Chemicals present in cigarette smoke, including established carcinogens like nicotine, can be absorbed in the lung and transported to distant sites by the blood.[7,8] Quantitative levels of cotinine, which is a major metabolite of nicotine, reflect recent smoking intensity. Smoke constituents, marked by cotinine concentration, have been found to concentrate in the cervix.[9,10] In women with in situ cancer of the cervix, cotinine and nicotine have been found to be more concentrated in cervical mucus than in serum.[6,11,12] The presence of nitrosamines, which are tobacco-specific carcinogens, have also been identified in the cervical mucus of smokers.[13]

Many chemical carcinogens exert their biological activity through covalent modification of DNA to form adducts. Some investigators have reported alterations in cellular nuclei, such as significantly higher DNA adducts, in smokers compared with nonsmokers. Simons and colleagues[14] noted that women with abnormal cervical smears had significantly higher DNA adduct levels than those with normal smears, suggesting that DNA modification in cervical epithelium may be caused by tobacco components. However, these investigators did not find a correlation with the number of cigarettes smoked daily. More data supporting an independent effect of smoking were reported by Ficorella and colleagues.[15] They identified the polycyclic aromatic hydrocarbon-DNA adducts in HPV-negative cervical neoplasia; this finding of a tobacco metabolite suggests an association between tobacco smoking and cervical neoplasia.

Langerhans' cells. Reductions in the numbers of Langerhans' cells (antigen-processing cells) have been observed in smokers and in patients with HPV infections.[16,17] Furthermore, the number of Langerhans' cells found in women with in situ cancer and HPV was reported to be substantially lower in current smokers than in women who had never smoked.[18]

Antioxidants and smoking. Nutritional studies have suggested that susceptibility to carcinogenic agents may be influenced by host levels of vitamin A and its precursor, beta-carotene. Ascorbic acid and beta-carotene, which are thought to facilitate DNA repair, have been shown to be diminished in the plasma of cigarette smokers with normal cervical cytology and further reduced in patients with cervical neoplasia.[19]

Carcinogens and HPV. Rorke and colleagues[20] recently reported that exposure to polycyclic hydrocarbons results in cervical apoptosis (ie, cervical cell self-destruction). However, HPV-immortalized ectocervical cells -- cells growing in a culture infected with HPV -- demonstrated altered cell responsiveness to polycyclic hydrocarbons and blocked apoptosis. These data suggest that the local effect of carcinogens is modulated by the presence of HPV infection. What seems to happen is this: Normally, cells die when exposed to the hydrocarbons and therefore do not undergo cell changes. However, HPV appears to prevent cell death, which allows the cells to develop neoplasia when exposed to carcinogens.

Enhanced susceptibility. Holly and colleagues[5] reported that women who smoked had a higher total number of cervical microorganisms than those who did not smoke, suggesting that smoking may alter the cervical microenvironment. This altered microenvironment may enhance susceptibility to infectious agents and/or carcinogens.

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