Co-infection with the bacteria that causes the sexually transmitted infection chlamydia and high-risk types of human papillomavirus (HPV) is associated with presence of high-grade pre-cancerous anal lesions in HIV-positive gay and bisexual men, Spanish researchers report in the online edition of Clinical Infectious Diseases. The presence of both infections was associated with an almost ninefold increase in the risk of having the pre-cancerous lesions known as high grade intraepithelial neoplasia (HGAIN).
Co-infection with Chlamydia trachomatis may potentiate the oncogenic capability of HPV16.
The researchers recommend that gay and bisexual men should be screened and when appropriate, treated, for anal infection with chlamydia.
“The results of our study point to local factors when looking for predictors of HGAIN besides high-risk HPV,” comment the authors. “Coinfection with Chlamydia trachomatis may potentiate the oncogenic capability of HPV16 so that when both pathogens coexist, the risk of HGAIN increases substantially compared with either infection alone in HIV-positive men who have sex with men. Accordingly, individuals coinfected with both pathogens would be at increased risk for the development of anal cancer.”
Anal cancer is one of the more common non-AIDS-defining cancers seen in people with HIV. Rates of the malignancy are especially high in HIV-positive gay and bisexual men.
Several high-risk strains of HPV – especially HPV16 – have been linked to the development of high grade pre-cancerous lesions, the precursor of anal cancer.
However, only a small portion of individuals infected with high risk HPV strains go on to develop pre-cancerous lesions and the malignancy. This suggests that other factors are involved in the development of HGAIN and anal cancer.
Co-infection with high risk HPV types and Chlamydia trachomatis is associated with the development of cervical cancer. To see if a similar relationship existed for HGAIN, a team of investigators led by Dr Mar Marsía designed a prospective study involving 145 HIV-positive gay and bisexual men. All underwent high resolution anoscopy to check for the presence of pre-cancerous lesions. Anal biopsies were also performed, with the tissue sample checked for 19 high-risk and nine low-risk HPV types for the development of pre-cancerous lesions. The tissue samples were also examined for the presence of seven bacteria that cause sexually transmitted infections, including Chlamydia trachomatis and Ureaplasma urealticum. The latter is most often associated with non-gonococcal urethritis, but may also be found in rectal samples.
Most of the men (86%) had an undetectable viral load and HGAIN was detected in almost a quarter (24%) of study participants. The CD4/CD8 ratio was lower among men with HGAIN (0.65 vs 0.75, p = 0.033). There were no differences between men with and without HGAIN in terms of demographics, viral suppression, frequency of hepatitis C virus co-infection, type of antiretroviral therapy and sexual behaviour.
DNA from high risk HPV types was detected in 84% of anal biopsies. The most common were HPV16 (26%), HPV52 (20%), HPV53 (19%) and HPV58 (19%).
After considering potential confounders, the investigators found that HPV16 was associated with HGAIN (aOR = 3.40; 95% CI, 1.41-8.87, p =0.008). Other HPV types associated with HGAIN were HPV53 (aOR = 2.79) and HPV70 (aOR = 4.24).
Anal infection with Chlamydia trachomatis was detected in 23% of men with HGAIN and 5% of those without. Rates of Ureaplasma urealyticum were also higher among men with HGAIN than men without high grade anal lesions (13% vs 31%).
After taking into account potential confounders, the investigators found that co-infection with Chlamydia trachomatis and HPV16 was the most important risk factor for the presence of HGAIN (aOR = 8.11; 95% CI, 2.16-31.04, p = 0.002). Importantly, these odds were significantly higher than that observed for any individual risk factor, such as infection with Chlamydia trachomatis (aOR = 3.78; 95% CI, 1.38-10.4, p = 0.01) or HPV16 (aOR = 2.45; 95% CI, 1.13-5.25, p = 0.022) alone. No interactions were found between other HPV types and STIs.
“Because of the high and growing frequency of infection with Chlamydia trachomatis in men who have sex with men and the paucity of related symptoms…screening and eventual therapy for this pathogen should be considered among measures to prevent anal cancer,” recommend the authors. “Additional anal local factors like the presence of HPV53 and HPV70 could also be linked to the development of HGAIN.”
Masía M et al. Infection with Chlamydia trachomatis increases the risk of high grade anal interaepithelial neoplasia in people living with HIV. Clin Infect Dis, online edition, doi: 10.1093/cid/ciz606, 2019.