Tobacco exposure and cervical cancer: attributable mortality from GBD 2021 and serum cotinine associations in NHANES 1999-2018

Abstract

Background: Persistent high-risk human papillomavirus (HPV) infection is the principal cause of cervical cancer, but modifiable cofactors such as tobacco exposure may influence HPV persistence and disease progression. This study integrated GBD 2021 smoking-attributable mortality estimates with NHANES 1999–2018 biomarker data to assess the population- and individual-level relevance of tobacco exposure to cervical cancer prevention.

Materials and Methods: GBD 2021 estimates were used to summarize female cervical cancer deaths attributable to smoking and unsafe sex globally and in China in 2021. NHANES analyses included nonpregnant women aged ≥20 years with serum cotinine data in the fasting analytic sample (n=9,899; 141 self-reported cervical cancer cases). Smoking status and serum cotinine levels were analyzed using survey weighted logistic regression with 20 multiple imputations.

Results: In GBD 2021, smoking accounted for an estimated 22,614 global female cervical cancer deaths (95% uncertainty interval [UI], 13,558–33,567), representing 7.6% (95% UI, 4.5–11.2) of deaths. In China, smoking accounted for 3,267 deaths (95% UI, 1,751–5,442), or 6.6% (95% UI, 3.6–10.0). In NHANES, current smokers had higher odds of cervical cancer than nonsmokers (adjusted odds ratio [OR], 2.97; 95% confidence interval [CI], 1.79–4.93). Each doubling of serum cotinine was associated with higher odds of cervical cancer (OR, 1.09; 95% CI, 1.06–1.13), and cotinine ≥3.00 ng/mL was associated with higher odds than cotinine <0.05 ng/mL (OR, 3.16; 95% CI, 1.94–5.16).

Conclusion: Smoking contributed a measurable proportion of cervical cancer mortality in GBD 2021, while current smoking and higher serum cotinine levels were associated with self-reported cervical cancer in NHANES. These cross-sectional associations do not establish causality but support considering tobacco cessation and reduction of smoke exposure as complementary components of cervical cancer prevention alongside HPV vaccination, screening, and timely treatment.