Abstract
Objectives: Few studies of smoking and cervical carcinoma have addressed the rare cervical adenocarcinomas or used DNA-based tests to control for human papillomavirus (HPV) infection.
Methods: This multicenter case–control study included 124 adenocarcinoma cases, 307 community controls (matched on age, race, and residence to adenocarcinoma cases), and 139 squamous carcinoma cases (matched on age, diagnosis date, clinic, and disease stage to adenocarcinoma cases). Participants completed risk-factor interviews and volunteered cervical samples for PCR-based HPV testing. Polychotomous logistic regression generated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for both histologic types.
Results: Eighteen percent of adenocarcinoma cases, 43% of squamous carcinoma cases, and 22% of controls were current smokers. After control for HPV and other questionnaire data, adenocarcinomas were consistently inversely associated with smoking (e.g. current: OR = 0.6, 95% CI 0.3–1.1; ≥1 pack per day: OR = 0.7, 95% CI 0.4–1.3), while squamous carcinomas were positively associated with smoking (e.g. current: OR = 1.6, 95% CI 0.9–2.9; ≥1 pack per day: OR = 1.8, 95% CI 1.0–3.3). Results in analyses restricted to HPV-positive controls were similar.
Conclusion: Smoking has opposite associations with cervical adenocarcinomas and squamous carcinomas. Although both histologic types are caused by HPV and arise in the cervix, etiologic co-factors for these tumors may differ.
Similar content being viewed by others
References
International Agency for Research on Cancer (1995) IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Vol. 64: Human Papillomaviruses. Lyon: International Agency for Research on Cancer.
Winkelstein W Jr (1990) Smoking and cervical cancer-current status: a review. Am J Epidemiol 131: 945-957.
Bosch FX, Manos MM, Munoz N, et al. (1995) Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biologic study on cervical cancer (IBSCC) study group. J Natl Cancer Inst 87: 796-802.
Walboomers JM, Jacobs MV, Manos MM, et al. (1999) Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 189: 12-19.
Rohan T, Mann V, McLaughlin J, et al. (1991) PCR-detected genital papillomavirus infection: prevalence and association with risk factors for cervical cancer. Int J Cancer 49: 856-860.
Schiffman MH, Brinton LA (1995) The epidemiology of cervical carcinogenesis. Cancer 76: 1888-1901.
Baron JA, Rohan TE (1996) Tobacco. In: Schottenfeld D, Fraumeni JF Jr, eds. Cancer Epidemiology and Prevention. New York: Oxford University Press, pp. 269-289.
Schiffiman MH, Brinton LA, DeVesa SS, Fraumeni JF Jr (1996) Cervical cancer. In: Schottenfeld D, Fraumeni JF Jr, eds. Cancer Epidemiology and Prevention. New York: Oxford University Press, pp. 1090-1116.
Vizcaino AP, Moreno V, Bosch FX, et al. (1998) International trends in the incidence of cervical cancer: I. Adenocarcinoma and adenosquamous cell carcinomas. Int J Cancer 75: 536-545.
Kjaer SK, Brinton LA (1993) Adenocarcinomas of the uterine cervix: the epidemiology of an increasing problem. Epidemiol Rev 15: 486-498.
Lacey JV Jr, Brinton LA, Abbas FM, et al. (1999) Oral contraceptives as risk factors for cervical adenocarcinomas and squamous cell carcinomas. Cancer Epidemiol Biomarkers Prev 8: 1079-1085.
Gravitt PE, Peyton CL, Apple RJ, Wheeler CM (1998) Genotyping of 27 human papillomavirus types by using L1 consensus PCR products by a single-hybridization, reverse line blot detection method. J Clin Microbiol 36: 3020-3027.
van den Brule AJ, Class EC, du Maine M, et al. (1989) Use of anti-contamination primers in the polymerase chain reaction for the detection of human papilloma virus genotypes in the cervical scrapes and biopsies. J Med Virol 29: 20-27.
Hosmer DW, Lemeshow S (1989) Applied Logistic Regression. New York: John Wiley & Sons.
Breslow NE, Day NE (1980) Statistical Methods in Cancer Research, Vol. I The Analysis of Case-Control Studies. IARC Scienti®c Publications No. 32. Lyon: International Agency for Research on Cancer.
SAS Institute Inc (1995) SAS Software: changes and enhancements, release 6.11. Cary, NC: SAS Institute Inc.
Shah BV, Barnwell BG, Bieler GS (1997) SUDAAN User's Manual, Release 7.5. Research Triangle Park, NC: Research Triangle Institute.
Franco EL (1991) The sexually transmitted disease model for cervical cancer: incoherent epidemiologic findings and the role of misclassification of human papillomavirus infection. Epidemiology 2: 98-106.
Phillips AN, Smith GD (1994) Cigarette smoking as a potential cause of cervical cancer: has confounding been controlled? Int J Epidemiol 23: 42-49.
Kjaer SK, van den Brule AJC, Svare EI, et al. (1998) Different risk factor patterns for high-grade and low-grade intraepithelial lesions on the cervix among HPV-positive and HPV-negative young women. Int J Cancer 76: 613-619.
Ho GYF, Kadish AS, Burk RD, et al. (1998) HPV 16 and cigarette smoking as risk factors for high-grade cervical intra-epithelial neoplasia. Int J Cancer 78: 281-285.
Bosch FX, Munoz N, de Sanjose S, et al. (1992) Risk factors for cervical cancer in Colombia and Spain. Int J Cancer 52: 750-758.
Yoshikawa H, Nagata C, Noda K, et al. (1999) Human papillomavirus infection and other risk factors for cervical intraepithelial neoplasia in Japan. Br J Cancer 80: 621-624.
Nobbenhuis MAE, Walboomers JMM, Helmerhorst TJM, et al. (1999) Relation of human papillomavirus status to cervical lesions and consequences for cervical-cancer screening: a prospective study. Lancet 354: 20-25.
Olsen AO, Gjoen K, Sauer T, et al. (1995) Human papillomavirus and cervical intraepithelial neoplasia grade II±III: a population-based case±control study. Int J Cancer 61: 312-315.
Brinton LA, Tashima KT, Lehman HF, et al. (1987) Epidemiology of cervical cancer by cell type. Cancer Res 47: 1706-1711.
Ursin G, Pike MC, Preston-Martin S, d'Ablaing G, Peters RK (1996) Sexual, reproductive, and other risk factors for adenocarcinoma of the cervix: results from a population-based case±control study (California, United States). Cancer Causes Control 7: 391-401.
Thomas DB, Ray RM, The WHO Collaborative Study of Neoplasia and Steroid Contraceptives (1996) Oral contraceptives and invasive adenocarcinomas and adenosquamous carcinomas of the uterine cervix. Am J Epidemiol 144: 281-289.
Parazzini F, La Vecchia C, Negri E, Fasoli M, Cecchetti G (1988) Risk factors for adenocarcinoma of the cervix: a case-control study. Br J Cancer 57: 201-204.
Brinton LA, Herrero R, Reeves WC, et al. (1993) Risk factors for cervical cancer by histology. Gynecol Oncol 51: 301-306.
Silcocks PBS, Thornton-Jones H, Murphy M (1987) Squamous and adenocarcinoma of the uterine cervix: a comparison using routine data. Br J Cancer 55: 321-325.
Ngelangel C, Munoz N, Bosch FX, et al. (1998) Causes of cervical cancer in the Philippines: a case±control study. J Natl Cancer Inst 90: 43-49.
Chichareon S, Herrero R, Munoz N, et al. (1998) Risk factors for cervical cancer in Thailand: a case±control study. J Natl Cancer Inst 90: 50-57.
Barton SE, Maddox PH, Jenkins D, et al. (1988) Effect of cigarette smoking on cervical epithelial immunity: a mechanism for neoplastic change? Lancet 2: 652-654.
Ylitalo N, Sorensen P, Josefsson A, et al. (1999) Smoking and oral contraceptives as risk factors for cervical carcinoma in situ. Int J Cancer 81: 357-365.
Hildesheim A, Schiffman MH, Gravitt PE, et al. (1994) Persistence of type-specific human papillomavirus infection among cytologically normal women. J Infect Dis 169: 235-240.
Ho GYF, Bierman R, Beardsley L, Chang CJ, Burk RD (1998) Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med 338: 423-428.
Simons AM, van Herckenrode CM, Rodriguez JA, et al. (1995) Demonstration of smoking-related DNA damage in cervical epithelium and correlation with human papillomavirus type 16, using exfoliated cervical cells. Br J Cancer 71: 246-249.
Simons AM, Phillips DH, Coleman DV (1993) Damage to DNA in cervical epithelium related to smoking tobacco. BMJ 306: 1444-1448.
McCann MF, Irwin DE, Walton LA, et al. (1992) Nicotine and cotinine in the cervical mucus of smokers, passive smokers, and nonsmokers. Cancer Epidemiol Biomarkers Prev 1: 125-129.
Hellberg D, Nilsson S, Haley NJ, Ho-man D, Wynder E (1988) Smoking and cervical intraepithelial neoplasia: nicotine and cotinine in serum and cervical mucus in smokers and nonsmokers. Am J Obstet Gynecol 158: 910-913.
Prokopczyk B, Cox JE, Hoffmann D, Waggoner SE (1997) Identification of tobacco-specific carcinogen in the cervical mucus of smokers and non-smokers. J Natl Cancer Inst 89: 868-873.
Parazzini F, La Vecchia C (1990) Epidemiology of adenocarcinoma of the cervix. Gynecol Oncol 39: 40-46.
Baron JA, La Vecchia C, Levi F (1990) The antiestrogenic effect of cigarette smoking in women. Am J Obstet Gynecol 162: 502-514.
Grady D, Ernster VL (1996) Endometrial cancer. In: Schottenfeld D, Fraumeni JF Jr, eds. Cancer Epidemiology and Prevention. New York: Oxford University Press, pp. 1058-1089.
Rose PG (1996) Endometrial carcinoma. N Engl J Med 335: 640-649.
Parazzini F, La Vecchia C, Negri E, Moroni S, Chatenoud L (1995) Smoking and risk of endometrial cancer: results from an Italian case-control study. Gynecol Oncol 56: 195-199.
Brinton LA, Barrett RJ, Berman ML, et al. (1993) Cigarette smoking and the risk of endometrial cancer. Am J Epidemiol 137: 281-291.
Lacey JV Jr, Brinton LA, Barnes WA, et al. (2000) Use of hormone replacement therapy and adenocarcinomas and squamous cell carcinomas of the uterine cervix. Gynecol Oncol 77: 149-154.
Shingleton HM (1993) Do squamous cell carcinomas and adenocarcinomas of the cervix have the same risk factors? Gynecol Oncol 51: 299-300.
Wright TC, Kurman RJ, Ferenczy A (1994) Precancerous lesions of the cervix. In: Kurman RJ, ed. Blaustein's Pathology of the Female Genital Tract. New York: Springer-Verlag, pp. 229-277.
Wright TC, Ferenczy A, Kurman RJ (1994) Carcinoma and other tumors of the cervix. In: Kurman RJ, ed. Blaustein's Pathology of the Female Genital Tract. New York: Springer-Verlag, pp. 279-326.
Wells AJ, English PB, Posner SF, Wagenknecht LE, Perez-Stable EJ (1998) Misclassification rates for current smokers misclassified as nonsmokers. Am J Public Health 88: 1503-1509.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lacey, J.V., Frisch, M., Brinton, L.A. et al. Associations between smoking and adenocarcinomas and squamous cell carcinomas of the uterine cervix (United States). Cancer Causes Control 12, 153–161 (2001). https://doi.org/10.1023/A:1008918310055
Issue Date:
DOI: https://doi.org/10.1023/A:1008918310055