Chlamydia trachomatis co-infection and cervical cancer risk in HPV-positive women: a cross-sectional and histological case-control study.

OBJECTIVES

To characterise Chlamydia trachomatis (CT)-HPV co-infection and test whether CT positivity is associated with cervical cancer in HPV-positive women.

METHODS

We conducted a two-component retrospective study at two southern Chinese tertiary hospitals (January 2022-June 2025). Component 1 comprised 21,205 women tested for CT and HPV. Component 2 comprised 100 HPV-positive invasive cervical cancers and 100 HPV-positive non-neoplastic controls, with CT detected by pgp3-PCR on tissue.

RESULTS

CT positivity was 3.36%, HPV 21.27%, co-infection 1.29%. CT was associated with HPV positivity (OR 2.38, 95% CI 2.04-2.78) in five of six age strata. Eight of 28 genotypes were associated with CT after Benjamini-Hochberg correction; HPV52, HPV58 and HPV53 were not (OR 0.92-1.30). CT-positive women had more multiple-genotype infections (45.1% vs 32.1%; OR 1.74, 95% CI 1.36-2.22). CT co-infection was associated with cancer risk (36% vs 18%; age-adjusted OR 2.53, 95% CI 1.31-4.88; HPV16-adjusted OR 2.29, 95% CI 1.08-4.89) and with high-grade tumour-infiltrating lymphocyte infiltration (exploratory; age-adjusted OR 2.75, 95% CI 1.07-7.08).

CONCLUSIONS

CT co-infection was associated with HPV positivity across the screened population and, at tissue level, with cervical cancer in HPV-positive women. The CT-HPV association was genotype-selective. Whether CT is a modifiable cofactor in HPV-positive women warrants prospective evaluation.