Order of HPV/Chlamydia infections and cervical high‐grade precancer risk: A case‐cohort study

Interactions of carcinogenic human papillomaviruses (most notably HPV types 16/18/31/33/45), and HPV6 or Chlamydia trachomatis are not well understood. We have used seroconversions to study effects the order of these infections has on the risk of high‐grade cervical precancer. In a cohort of 94,349 Finnish women with paired sera from consecutive pregnancies within an average of 2.4 years, 490 were diagnosed with cervical CIN3/AIS. Serum antibodies to HPV6/16/18/31/33/45 and C. trachomatis were measured in paired sera of the cases and a subcohort of 2,796 women with a minimum of two pregnancies. HPV16‐adjusted rate ratios (RR) and confidence intervals were estimated by stratified Cox model. Compared to dual seropositivity already at the first serum sampling, RRs related to HPV6 seropositivity before and after HPV31 seroconversion were 0.4 (95% CI 0.0, 4.4) and 10 (95% CI 1.8, 57). Furthermore, RR related to seroconversions of both HPV18/45 and C.trachomatis between the consecutive pregnancies was 28 (95% CI 4.3, 190). Virtually concomitant HPV18/45 and C.trachomatis infections are associated with very high CIN3 risk. What's new? Infection with high‐risk human papillomaviruses (hrHPVs), such as HPV16, is a well‐known cause of cervical cancer. But it is unclear whether a chain of events, such as infection with low‐risk HPVs or with Chlamydia trachomatis, precedes hrHPV transformation of cervical cells. Here, a 28‐fold increase in risk for cervical precancer, CIN3, was detected among women exposed to both HPV type 18/45 and C. trachomatis between pregnancies compared with women seropositive for the infections at the first pregnancy. The data support early HPV vaccination and screening for hrHPV for cervical cancer prevention.