Prior Chlamydia Infection and Doubled Risk for Ovarian Cancer

Alexander M. Castellino, PhD

March 20, 2018

In two independent populations, prior infection with Chlamydia appeared to double the risk for ovarian cancer, according to data presented at a presscast in advance of the American Association for Cancer Research (AACR) 2018 Annual Meeting.

Presenter Britton Trabert, PhD, Earl Stadtman Investigator in the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, explained that pelvic inflammatory disease (PID), which is caused when bacteria infect the uterus, fallopian tubes, and ovaries, is associated with increased risk for ovarian cancer. Chlamydia is the leading cause of PID in the Western world.

Chlamydia infection is challenging to diagnose, because it is often asymptomatic, and ascertaining PID in epidemiologic studies is challenging owing to misclassification or underreporting, Trabert noted.

The team used a serologic marker for Chlamydia infection — antibodies against Pgp3, which is a gold standard for identifying past and current Chlamydia infection.

They report that in a case-control study conducted in Poland that involved 278 patients with ovarian cancer and 556 age- and study-site matched control persons, patients with antibodies against Pgp3 were at a 63% increased risk for ovarian cancer (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.20 - 2.22). When the positive result was defined at a higher titer, risk for ovarian cancer doubled (OR, 2.00; 95% CI, 1.38 - 2.89).

Trabert and colleagues confirmed these results in an independent, prospective, case-control cohort from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, which included 160 women who eventually developed ovarian cancer and 159 matched control persons. In the PLCO cohort, patients with antibodies against Pgp3 were at a 43% increased risk for ovarian cancer (OR, 1.43; 95% CI, 0.78 - 2.63). Again, at the higher and more stringent cutoff threshold, risk for ovarian cancer more than doubled (OR, 2.25; 95% CI, 1.07 - 4.71).

In both the Polish and PLCO cohorts, markers of other infections were not associated with increased ovarian cancer risk. The researchers tested markers for Mycoplasma genitalium, herpes simplex virus 2, human papillomavirus, polyomavirus, hepatitis B, hepatitis C, Epstein-Barr virus, and cytomegalovirus.

"The fact that there were no associations with antibodies against other infections supports the specificity of the association of Chlamydia infection with ovarian cancer," Trabert said.

She noted that a limitation of the study was that the multiplex platform used was not able to reliably test for antibodies to Neisseria gonorrhoeae, another known cause of PID.

Elaine Mardis, PhD, who was comoderator of the presscast and is program chair of the 2018 AACR annual meeting and coexecutive director of the Institute for Genomic Medicine at the Nationwide Children's Hospital in Columbus, Ohio, said: "Ovarian cancer is typically diagnosed at a late stage and is associated with poor prognosis. In this study, the evaluation of a common agent of sexually transmitted disease, namely, Chlamydia, was an important point of the study as it [Chlamydia infection] is asymptomatic and difficult to diagnose."

She also noted the importance of utilizing the Polish and PLCO cohorts, through which the investigators were able to obtain a sufficient number of samples from different parts of the world.

"The study emphasizes the international flavor of cancer research that can be found at the AACR annual meeting," she said.

However, the finding does not have practical applications at present. Trabert told Medscape Medical News: "Based on our study, we cannot recommend screening for markers of Chlamydia for early detection of ovarian cancer.

"Replication of our results is necessary," she said. "Once our results are replicated, additional studies will need to be conducted to evaluate whether ovarian cancer can be reduced through treatment of Chlamydia infections and/or PID," she added.

Trabert also indicated that future studies will determine whether treating Chlamydia and PID will reduce the risk for ovarian cancer.

Dr Trabert has disclosed no relevant financial relationships.

American Association for Cancer Research (AACR) 2018 Annual Meeting. Abstract 4942, to be presented April 17, 2018.

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