Introduction: Bacterial vaginosis, a modification of the vaginal microbiota, is positively associated with the acquisition of certain genital infections, including cervical human papillomavirus (HPV) infection. In turn, HPV infection is the chief etiologic agent in the development of cervical cancer. Although HPV infection is widely prevalent, only few infected women will develop cervical cancer, suggesting that environmental or host factors contribute to malignancy. In this study, we are interested in identifying if the enzyme indoleamine-2,3-dioxygenase (IDO) has a role in the mechanism by which BV contributes to HPV infection and cervical lesion. IDO catalyzes the oxidation of the essential amino acid tryptophan (Trp) to kynurenine. IDO expression is induced by IFN-gamma and has been linked to T-cell immunosuppression and immune tolerance. IDO also plays an important role in host–pathogen interactions during viral and bacterial infections and on immune-escape of cancer cells.
Methods: This cross-sectional study included 296 women attending the Women's Hospital - CAISM/UNICAMP. The case group was composed of women who had a confirmed histologic diagnosis of cervical intraepithelial neoplasia (CIN) grade 1, 2, or 3 or squamous cell carcinoma (SCC). The control group was composed of women who presented at least two previous normal Pap smears. The levels of IDO expression were analyzed by immunocytochemistry in liquid-based cytology samples from 196 women. Score 1 and 2 (0 to 50% of DAB stained squamous cells) were considered as mild expression and Score 3 and 4 (51 to 100% of DAB stained squamous cells) were considered as strong expression. Immunocytochemical analysis considered both atypical and typical squamous in the counting. The Gram-stained slides were analyzed by Nugent criteria. We used the Linear Array Genotyping HPV kit for detection of 37 types of low- and high-risk HPVs. Multiplex PCR was performed for the diagnosis of Chlamydia trachomatis (Ct), Neisseria gonorrhoeae (Ng), and Trichomonas vaginalis. Study variables were evaluated by odds ratio (OR) with a 95% confidence interval (CI) and Qui-square test and significance level was defined at 5%.
Results: BV was positively associated with genital infection by HPV (p = 0.02), Trichomonas vaginalis (p=0.001) and endocervicitis by Ct and Ng (p= 0.000003). We found a higher frequency of strong expression of IDO (74%, 31/42) in women with BV when compared with women without BV (44%, 60/137 and p= 0.0007). Although the expression of IDO was slightly greater for HPV infection associated with BV (62%, 15/24), and women with CIN1 and CIN3 had a slightly higher frequency of IDO expression, these associations were not statistically significant. No correlation was found for IDO and CIN2, CIN3, or SCC.
Conclusion: Here we show that IDO is upregulated in BV but is not associated with the severity of cervical lesion. We also found that BV is positively associated with genital infection by HPV. We suggest that upregulation of IDO in BV could be one of the cofactors that lead to an increased risk of HPV coinfection, whose importance is attenuated during cervical lesion progression. Ongoing studies are focused on the analysis of IDO expression, specifically in the atypical cells of cervical lesions.
Citation Format: Paloma Almeida Venancio, Silvya Stuchi Maria-Engler, Marcia Edilaine Lopes Consolaro, Luisa Lina Villa, Sophie Françoise Derchain, Ana Campa, Michelle Garcia Discacciati. Upregulation of IDO in bacterial vaginosis: Role in HPV coinfection [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A46.