Relationship between smoking, HPV infection, and risk of cervical cancer

Purpose of investigation: To document the relationship between smoking and HPV infection, and the risk of developing preinvasive lesions and cervical carcinoma. Materials and Methods: Prospective, cross-sectional descriptive study. A total of 1,007 patients were recruited among women seen at the cervical pathology clinic of Sant Joan de Deu University Hospital in Barcelona (Spain) between January 2003 and March 2011. Patients were asked specifically about their smoking habits. Statistical analyses were done with SPSS v.19 software. Differences between groups were considered statistically significant at p < 0.05. Results: In patients studied, 48.7% were smokers. The average number of cigarettes per day among smoking patients was 7.07 (1-40). In the of patients with HPV infection, 53% were smokers versus 37% of patients without HPV infection (p < 0.05). The average number of cigarettes per day among patients with HPV infection was 7.64 cigarettes/day versus 5.55 cigarettes/day among patients without HPV infection (p < 0.05). In the patients with high-risk HPV genotypes infection, 54.5% were smokers versus 43.2% of patients without high-risk HPV infection (p < 0.05). Risk of HPV infection increases 1.905 times among smoking patients versus no smoking patients (OR = 1.905, CI 95% (1.426 - 2.545), p < 0.05). Among patients with changes associated to HPV and atypical cells, there were 29.2% and 14.4% of smokers, respectively, versus 45.5%, 55.6%, and 48.6% of smokers among patients with grade 1 cervical intraepithelial neoplasia (CIN 1), CIN 2-3, and carcinoma, respectively (p < 0.05). Risk of CIN 2-3 or cervical carcinoma cervical increases 1.642 times among smoking patients versus no smoking ones (OR = 1.642, CI 95% (1.325 - 1.884), p < 0.05). Conclusions: Smoking interferes in the increase of HPV infection prevalence and in an increased risk of CIN and cervical carcinoma. Risk also increases with more cigars smoked per day.

Human papillomavirus infection; Cervical cancer; Cervical intraepithelial neoplasia Grade 1, 2, 3; Smoking.

[1] Castellsagué X., Muñoz N.: “Cofactors in human papillomavirus carcinogenesis-role of parity, oral contraceptives and tobaco smoking”. J. Natl. Cancer Inst. Monogr., 2003, 31, 20.

[2] Kjellberg I., Hallmans G., Ahren A.M., Johansson R., Bergman F., Wadell G., et al.: “Smoking, diet, pregnancy and oral contraceptive use are risk factors for cervical intraepithelial neoplasia in relation to humanpapillomavirus infection”. Br. J. Cancer, 2000, 82, 1332.

[3] Hidesheim A., Herrero R., Castle P.E., Wacholder S., Bratti M.C., Sherman M.E., et al.: “HPV co-factors related to the development of cervical cancer: results from a population-based study in Costa Rica”. Br J Cancer, 2001, 84, 1219.

[4] Trimble C.I., Genkinger J.M., Burke A.E., Hoffman S.C., Helzlsouer K. J., Diener-West M., et al.: “Active ans passive cigarette smoking and the risk of cervical neoplasia”. Obtet. Gynecol., 2005, 105, 174.

[5] Szrewski A., Jarvis M., Sasieni P., Anderson M., Edwards R., Steele S. J., et al.: “Effect of smoking cessation on cervical lesion size”. Lancet, 1996, 347, 941.

[6] Mazarico E., González-Bosquet E.: “Prevalence of infection by dif-ferent genotypes of human papillomavirus in women with cervical pathology”. Gynecol. Oncol., 2012, 125, 181.

[7] Castellsague X., Muñoz N.: “Cofactos in human papillomavirus carcinogenesis-role of parity, oral contraceptives and tobacco smoking”. J. Nat. Cancer Inst. Monogr., 2003, 31, 20.

[8] Giuliano A.R., Sedjo R.L., Roe D.J., Harri R., Baldwi S., Papenfuss M.R., et al.: “Clearance of oncogenic human papillomavirus infection: effect of smoking (United States)”. Cancer Causes Control, 2002, 13, 839.

[9] International Collaboration of Epidemiological Studies of Cervical Cancer: “Cervical carcinoma and sexual behavior: collaborative re-analysis of individual data pn 15.461 women with cervical carcinoma and 29.164 women without cervical carcinoma from 21 epidemiological studies”. Cancer Epidemiol. Biomarkers Prev., 2009, 18, 1060.

[10] International Collaboration of Epidemiological Studies of Cervical Cancer: “Comparison of risk factors for invasive squamous cell car-cinoma and adenocarcinoma of the cervix: collaborative reanalysis of individual data on 8,097 women with squamous cell carcinoma and 1,374 women with adenocarcinoma from 12 epidemiologial studies”. Int. J. Cancer, 2006, 120, 885.

[11] Gargano J., Nisenbaum R., Lee D., Ruffin M., Steinau M., Horowitz I., et al.: “Age-Group differences in Human Papillomavirus types and cofactos for cervical intraepithelial neoplasia 3 among women referred to colposcopy”. Cancer Epidemiol. Biomarkers Prev., 2012, 21, 111.

[12] Wang S., Zuna R., Wentzensen N., Dunn S., Sherman M., Gold M., et al.: “Human Papillomavirus cofactors by disease progression and human papilomavirus types in the study to understans cervical cancer early endpoints and determinants”. Cancer Epidemiol. Biomarkers Prev., 2009, 18, 113.

[13] Louie K., Castellsague X., de Sanjose S., Herrero R., Meijer C., Shah K., et al.: “Smoking and passive smoking in cervical cancer risk: pooled analysis of couples from the IARC multicentric case-control studies”. Cancer Epidemiol. Biomarkers Prev., 2011, 20, 1379.

[14] Xi L., Koutsky L., Castle P.E., Edelstein Z., Meyers C., Ho J., et al.: “Relationship between smoking and human papilomavirus types 16 and 18 DNA load”. Cancer Epidemiol. Biomarkers Prev., 2009, 18, 3490

[15] Castellsague X., Muñoz N.: “Cofactors in human papillomavirus carcinogenesis-role of parity, oral contraceptives and tobacco smoking”. J. Nat. Cancer Inst. Monogr., 2003, 31, 20.

[16] Yetimalar H., Kasap B., Cukurova K., Yildiz A., Keklik A., Soylu F.: “Cofactors in human papillomavirus infection and cervical carcinogenesis”. Arch. Gynecol. Obstet., 2012, 285, 805.

[17] Gadducci A., Barsotti C., Cosio S., Domenici L., Genazzani A.: “Smoking habit, immune suppression, oral contraceptive use and hormone replacement therapy and cervical carcinogenesis: a review of literature”. Gynecol. Endocrinol., 2011, 27, 597.

[18] Plummer M., Herrero R., Franceschi S., Meijer C.J., Snijders P., Bosch F.X., et al.: “Smoking and cervical cancer: pooled analysis of the IARC multicentric case–control study”. Cancer Causes Control, 2003, 14, 805.

[19] Buckley J.D., Harris R.W., Doll R., Vessey M.P., Williams P.T.: “Case-control study of the husbands of women with dysplasia or carcinoma of the cervix uteri”. Lancet, 1981, 2, 1010.

[20] Matsumoto K., Oki A., Furuta R., Maeda H., Yasugi T., Takatsuka N., et al.: “Tobacco smoking and regression of low-grade cervical abnormalities”. Cancer Sci., 2010, 101, 2065.