Dose-risk relationships between cigarette smoking and cervical cancer: a systematic review and meta-analysis

Abstract

Objective Cervical cancer (CC) is the fourth most frequent cancer worldwide. Cigarette smoking has been shown to influence CC risk in conjunction with human papillomavirus (HPV) infection. The aim of this study is to provide the most accurate and updated estimate of this association and its dose-response relationship. Methods Using an innovative approach for the identification of original publications, we conducted a systematic review and meta-analysis of studies published up to January 2021. Random effects models were used to provide pooled relative risks (RRs) of CC for smoking status. Dose-response relationships were evaluated using one-stage random effects models with linear or restricted cubic splines models. Results We included 109 studies providing a pooled RR of invasive CC and preinvasive lesions, respectively, of 1.70 [95% confidence interval (CI), 1.53–1.88] and 2.11 (95% CI, 1.85–2.39) for current versus never smokers, and, respectively, 1.13 (95% CI, 1.02–1.24) and 1.29 (95% CI, 1.15–1.46) for former versus never smokers. Considering HPV does not alter the positive association or its magnitude. Risks of CC sharply increased with few cigarettes (for 10 cigarettes/day, RR = 1.72; 95% CI, 1.34–2.20 for invasive CC and RR = 2.13; 95% CI, 1.86–2.44 for precancerous lesions). The risk of CC increased with pack-years and smoking duration and decreased linearly with time since quitting, reaching that of never smokers about 15 years after quitting. Conclusion This comprehensive review and meta-analysis confirmed the association of smoking with CC, independently from HPV infection. Such association rose sharply with smoking intensity and decreased after smoking cessation.

Risk Analysis Stratification of CIN 2+ Development in a Cohort of Women Living with HIV with Negative Pap Smear and HR-HPV Test during a Long-Term Follow-Up

“…In particular, NK activities in smokers are significantly reduced in comparison to those of non-smokers, and smoking seems to promote the acquisition or persistence of HPV infection through a reduction in the number of CD4+ lymphocytes, Langerhans cells, and local immune responses in the cervix [ 32 , 33 , 34 ]. These data are confirmed by a recent review and meta-analysis that showed a positive association between smoking and cervical cancer, independently from HPV infection, indicating that this association is dose-related and declines after the interruption of smoking [ 35 ]. In WLWH, the destruction of CD4+ cells by HIV combined with the effect of smoke may increase the likelihood of persistent HPV and the development of HPV-related lesions.…”

Risk factors for the increasing incidence of pregnancy‐associated cancer in Sweden – a population‐based study

“…24,25 Our finding of an increased risk of cervical cancer during pregnancy among smokers was expected, considering that smoking is a well-established risk factor for cervical cancer. 26 However, this has not previously been reported for PAC and was in contrast to the null finding for smoking and cervical cancer within 1 year post-delivery.…”

“…There was a borderline association between immigrant background and lower risk of pregnancy‐associated cervical cancer both during and after pregnancy, which is likely due to a lower screening attendance among foreign‐born women 24,25 . Our finding of an increased risk of cervical cancer during pregnancy among smokers was expected, considering that smoking is a well‐established risk factor for cervical cancer 26 . However, this has not previously been reported for PAC and was in contrast to the null finding for smoking and cervical cancer within 1 year post‐delivery.…”

Risk factors for the development of cervical cancer: analysis of the evidence

“…The risk increases to over 2 with a habit of approximately 20 cigarettes/day or 15 pack-years for invasive CC and about nine cigarettes/day or eight pack-years for preinvasive lesions. However, the risk subsides about 15 years after cessation of smoking ( 51 ). In terms of passive smoking as a risk factor for CC, the results are inconsistent.…”