SUMMARY
OBJECTIVE:
The objective of this study was to assess the clinical and uterine cervix characteristics of patients displaying vaginal discharge with positive results for Mycoplasma sp. and/or Ureaplasma spp.
METHODS:
An analytical cross-sectional study involving women aged 18–45 years was conducted. Microbiological assessments included Ureaplasma and Mycoplasma cultures, as well as human papillomavirus hybrid capture using ecto and endocervix swabs. All tests were two-tailed, and significance was set at p<0.05.
RESULTS:
Among 324 women, Ureaplasma prevalence was 17.9%, and Mycoplasma prevalence was 3.1%. The Ureaplasma-positive group exhibited a higher frequency of urinary tract infections (39.1 vs. 19%, p=0.002) and human papillomavirus (39.7 vs. 12.8%, p≤0.001) compared with controls. The Mycoplasma-positive group showed a higher frequency of non-contraceptive use compared with controls (66.2 vs. 30.0%, p=0.036). Abnormal colposcopic findings were more prevalent in the Mycoplasma/Ureaplasma-positive group than in controls (positive: 65% vs. control: 35%, p=0.001). Pap smear findings did not differ between the groups.
CONCLUSION:
Ureaplasma spp. was associated with urinary tract infections and human papillomavirus, while the presence of Mycoplasma sp. was linked to reduced contraceptive use. When analyzing both pathogens together, a higher frequency of abnormal colposcopic findings was observed, with no difference in cytological findings in the positive group.
KEYWORDS: Mycoplasma, Uterine cervicitis, HPV, Cervix
INTRODUCTION
The prevalence of vaginal colonization by Mycoplasma sp. and Ureaplasma spp. among women tends to increase post-puberty, correlating with the number of sexual partners over their lifetime. While some authors characterize these microorganisms as commensal residents, they are also linked to various pathological conditions, including premature birth, vaginal discharge, urethritis, pelvic inflammatory disease, and infertility 1-3 .
Exposure of the cervicovaginal epithelium to Mycoplasma sp. and Ureaplasma spp. may give rise to a persistent intracellular infection, potentially leading to tissue damage mediated by inflammatory cytokines. Although the relationship between human papillomavirus (HPV) and these microorganisms is not conclusively established, the nature of the infection they cause allows for both direct interaction with HPV during co-infection of a single cell and indirect interaction through cytokine responses 4 .
Several studies indicate that the presence of Mycoplasma bacteria heightens the risk of more severe cervical lesions, such as low- and high-grade intraepithelial lesions 5 . In addition, women with abnormal cervical cytologies exhibit a 17.6 times greater risk for co-infection with Mycoplasma hominis and Ureaplasma urealyticum 6 .
However, studies assessing the relationship between Ureaplasma/Mycoplasma and cervical cell changes are controversial. In 2018, a study examined the association between M. hominis infection and abnormal cervical cells but found no correlation between bacterial infections and abnormal cervical cytology 7 . Another study investigated the relationship between Mycoplasma, Ureaplasma, and HPV infections in sex workers, also failing to identify a correlation between M. hominis, U. urealyticum, and HPV infection 8 .
Contrary to these findings, it has been observed that high-risk HPV (hr-HPV) infection is a necessary cause of cervical cancer. However, other common microbes in the lower genital tract may enhance hr-HPV infection and cervical cytopathy 9 . The association of co-infection between HPV and sexually transmitted infections was compared using cervical samples from women with cervical dysplasia. Significant correlations were found between HPV, sexually transmitted infections, abnormal cervical cytology, HPV status, types of sexually transmitted infections, and the presence of Ureaplasma spp. and M. hominis 10 .
To clarify the importance of Mycoplasma/Ureaplasma infection in the uterine cervix, this study aimed to describe the gynecological clinical data and uterine cervix alterations in patients presenting with vaginal discharge and positive results for Mycoplasma sp. and Ureaplasma spp.
METHODS
An analytical cross-sectional study was conducted following the guidelines outlined in the STROBE statement 11 . The study took place between 2022 and 2025 in a private health service located in a region of northeastern Brazil with a Human Development Index (HDI) of 0.63.
The inclusion criteria encompassed women aged 18–45 years, with an active sexual life and complaints of non-physiological vaginal discharge. Exclusion criteria comprised menopausal status, genital bleeding during examination, immunosuppression, pregnancy, incomplete medical records, and hysterectomy.
Clinical data were collected by reviewing patient medical records and documented on a study-specific form. Variables included age, menarche age, number of sexual partners, obstetric history, parity, abortions, contraceptive method, urinary tract infections (UTIs), HPV status, characteristics of vaginal discharge (odor and itching), and cultures for Ureaplasma spp. and Mycoplasma sp. Reports related to colposcopic, cytological, and microbiological examinations were also consulted.
Colposcopic findings were categorized as normal, abnormal, or miscellaneous. Cytological findings were classified as unsatisfactory, normal (including normal smears and inflammation/cytolysis), and abnormal (ASC-US, ASC-H, ACG, LIEBG, and LIEAG).
The sample selection involved individuals classified as "Positive for Ureaplasma" and/or "Positive for Mycoplasma" constituting the case group, and those labeled "Negative for Ureaplasma" and "Negative for Mycoplasma" forming the control group. In addition, the presence of Candida sp., Gardnerella, and HPV was also investigated.
Diagnosis of Ureaplasma and Mycoplasma was obtained through microbiological culture using semi-liquid medium A/3 and A/7 specific to these microorganisms. The Sabouraud-Agar culture was utilized for diagnosing fungi and hybrid capture for HPV. The presence of Gardnerella was indicated by the identification of clue cells in the Pap smear and the presence of an odor. Patients with dysuria or hematuria underwent a urine culture and antibiogram to evaluate urinary infection.
Numerical and categorical data from the collected information were tabulated and statistically analyzed using the SPSS (Statistical Package for the Social Sciences) program version 14.0 (SPSS Inc., Chicago, IL, USA). An inductive/inferential analysis was conducted to describe the population and compare the groups. The Student's t-test was employed for quantitative variables with a normal distribution, the Mann-Whitney test was used for non-normally distributed quantitative variables, and the chi-square test was used for variables with n>5, with Fisher's exact test applied when n<5 for qualitative variables. All tests were two-tailed, with a significance level set at 5% (p<0.05) and a confidence interval of 95%.
Ethics
The study adhered to the ethical and legal standards outlined in Resolution 466/12 of the National Health Council and received approval from the research ethics committee of the Fundação Bahiana para Desenvolvimento das Ciências, under CAAE number 6333520.5.0000.5544. Furthermore, the study was conducted by the Declaration of Helsinki and its subsequent revisions.
RESULTS
Initially, 404 patients were enrolled, with 80 subsequently excluded based on pre-established exclusion criteria. Ultimately, 324 women of reproductive age were selected, among whom 58 tested positive for Ureaplasma spp., 10 tested positive for Mycoplasma sp., and 256 had negative cultures for these microorganisms.
The prevalence rates were 3.1% (10/324) for Mycoplasma sp. and 17.9% (58/324) for Ureaplasma spp. Coital activity was more common among individuals aged 10–20 years (81.01%). Most reported having one to five sexual partners, with 67.1% having never been pregnant and 81.8% having no history of abortion. The majority (65.1%) used some form of contraceptive method. Notably, white discharge without odor or itching was prevalent in the sample (56.8%).
In the bivariate analysis, only the presence of HPV was associated with Ureaplasma infection, even after adjusting for confounding variables (OR: 17.42, 95%CI: 3.08–161.2, p=0.004). Regarding Mycoplasma infection, only the use of contraceptives proved to be a protective factor (OR: 0.23, 95%CI: 0.005–0.86, p=0.038). Among the patients studied, 211 (65.1%) were using a contraceptive method. The most used method was hormonal contraceptives (56.4%), in both its oral and injectable versions, followed by the variable of patients not using contraceptive methods (34.9%). The male condom was used for 52 (24.6%) of the patients' partners.
Analysis of co-infections revealed that the presence of Ureaplasma spp. occurred simultaneously with HPV infection in 39.7% (n=23) of cases, showing a significant difference (p=0.001) and a moderate strength of association (contingency coefficient=0.261). However, there is a higher likelihood of patients with non-physiological genital flow being negative for both infections, accounting for 87.2% (n=232) in our sample. Further examination of HPV positivity within groups revealed an uneven distribution (p=0.001), with a higher frequency of oncogenic HPV. In the Ureaplasma-positive group, the frequency of oncogenic HPV was 22.4% (n=13). Other infections did not show differences (Table 1).
Table 1. Description of data on the presence and absence of infections in the group of patients positive or negative for Ureaplasma sp.
| Variables | n | Ureaplasma sp. n (%) | p-value | OR | ||
|---|---|---|---|---|---|---|
| Negative | Positive | |||||
| HPV | 0.001 | |||||
| Negative | 267 | 87.2% (232) | 60.3% (35) | 1.44 | ||
| Positive | 57 | 12.8% (34) | 39.7% (23) | 0.32 | ||
| HPV | 0.001 | |||||
| Non-oncogenic | 11 | 3% (8) | 5.2% (3) | |||
| Oncogenic | 30 | 6.4% (17) | 22.4% (13) | |||
| Non-oncogenic and Oncogenic | 16 | 3.4% (9) | 12.1% (7) | |||
| Fungus | 0.847 | |||||
| Negative | 293 | 90% (240) | 91.4% (53) | 0.99 | ||
| Positive | 30 | 9.4% (25) | 8.6% (5) | 1.0 | ||
| Gardnerella | 0.573 | |||||
| Positive | 16 | 4.9% (13) | 5.2% (3) | 0.94 | ||
| Negative | 308 | 93.6% (300) | 2.4% (8) | 1.0 | ||
Regarding co-infections involving HPV and Mycoplasma, it was noted that most cases tested negative for both HPV and Mycoplasma, comprising 83.1% (n=261) of the total cases. Among those cases that tested positive for Mycoplasma, 60% (n=6) were negative for HPV (OR=1.38). However, this association demonstrated a weak correlation (contingency coefficient=0.104) and lacked statistical significance between the groups (p=0.079). In the case of Fungi and Gardnerella, both exhibited higher percentages of negative cases in both groups, those with and without Mycoplasma. The analysis of the two infections revealed a greater occurrence of patients in the sample but did not indicate simultaneous infection with Mycoplasma (OR Fungi=1.14; OR Gardnerella=1.0). Nevertheless, no differences were identified in the studied groups for both fungi (p=0.235) and Gardnerella (p=0.403) (Table 2).
Table 2. Description of data on the presence and absence of infections in the group of patients positive or negative for Mycoplasma sp.
| Variables | n | Mycoplasma sp. n (%) | p-value | OR | ||
|---|---|---|---|---|---|---|
| Negative | Positive | |||||
| HPV | 0.079 | |||||
| Negative | 267 | 83.1% (261) | 60% (6) | 1.38 | ||
| Positive | 57 | 16.9% (53) | 40% (4) | 0.42 | ||
| HPV | 0.001 | |||||
| Non-oncogenic | 11 | 2.5% (8) | 30% (3) | |||
| Oncogenic | 30 | 9.2% (29) | 10% (1) | |||
| Non-oncogenic and oncogenic | 16 | 5.1% (16) | 0% (0) | |||
| Fungus | 0.235 | |||||
| Negative | 293 | 91.1% (285) | 80% (8) | 1.14 | ||
| Positive | 30 | 8.9% (28) | 20% (2) | 0.45 | ||
| Gardnerella | 0.403 | |||||
| Negative | 307 | 95.2% (298) | 90% (9) | 1.0 | ||
| Positive | 16 | 4.8% (15) | 10% (1) | 0.48 | ||
DISCUSSION
We observed a prevalence of 3.08% for Mycoplasma sp. and 17.9% for Ureaplasma spp. among women reporting non-physiological vaginal discharge. The higher prevalence of Ureaplasma compared with Mycoplasma aligns with previous studies where Ureaplasma spp. values ranged from 4.8 to 48.07%, while Mycoplasma sp. values varied between 0.8 and 23.4% 12-15 .
Contrary to this pattern, some studies reported a higher prevalence of Mycoplasma than Ureaplasma. For instance, Cardillo found 35.89% for Mycoplasma spp. and 25.54% for U. urealyticum 15 , and Christofolini et al. 16 found 11.3% for M. hominis and 0.94% for U. urealyticum. Such discrepancies in frequency among studies may result from variations in the populations studied and the techniques used to detect microorganisms 12,17 .
Furthermore, we identified an association between Ureaplasma infection and UTIs, consistent with a 2020 meta-analysis by Moridi et al. 17 evaluating the prevalence of M. hominis, Mycoplasma genitalium, and U. urealyticum among Iranian couples. They reported a U. urealyticum prevalence of 17.53% and an M. hominis prevalence of 9.68%, noting higher infection rates in women with symptoms of genito-UTI compared with men with UTI (7.67% vs. 5.88 and 21.04% vs. 12.13%, respectively).
Recent studies propose a potential interference of M. hominis, U. urealyticum, and Ureaplasma parvum with HPV infection, leading to virus persistence. Some studies found a positive relationship between U. urealyticum and HPV, while others reported an overall correlation between Ureaplasma spp. and M. hominis with HPV9 10,12,14,18 . Our study aligns with these findings, showing a significant relationship between Ureaplasma spp. and the presence of HPV. However, contradicting these results, a 2018 Indonesian study concluded no connection between Ureaplasma and Mycoplasma sp. and HPV 8 .
Additionally, a study by Zdrodowska-Stefanow et al. 14 demonstrated that the risk of HPV infection doubled when a woman was infected with any of the four species of Mycoplasma. In cases of concomitant U. urealyticum infection, the risk of HPV infection was 4.7 times higher. In contrast, another study from 2018 concluded that Ureaplasma spp. and Mycoplasma sp. were not linked to HPV 12 . The complexity of these relationships underscores the need for further research and genotyping of Ureaplasma spp. species 14 .
Regarding colposcopic findings, we noted a higher prevalence of abnormal results in positive patients, contrasting with a study reporting inconclusive colposcopy outcomes in patients with U. urealyticum and M. hominis 15 . However, concerning cytological findings in our study, no significant association was observed. This aligns with the study by Effiana et al., which found no relationship between M. hominis and altered Pap smear results 7 . Yet, earlier studies demonstrated that U. urealyticum, U. parvum, and M. hominis may increase the risk of cytological changes in the uterine cervix 8,9,10 .
The influence of the vaginal microbiome on the development of neoplastic lesions in the uterine cervix has been documented in previous studies. While some reported the relevance of Mycoplasma sp. and Ureaplasma spp. in the context of cervical cancer 8,14,16 , others did not find a clear relationship with the onset and progression of CIN 8,17 . The varied findings emphasize the intricacies of these interactions and the need for future investigation in this field.
CONCLUSION
Ureaplasma spp. was more prevalent and associated with UTI and HPV, whereas Mycoplasma sp. was linked to reduced contraceptive use. In addition, abnormal colposcopic findings were more prevalent in patients positive for Ureaplasma spp. and/or Mycoplasma sp.
However, more robust studies are needed to explore the interrelationship of Ureaplasma and Mycoplasma with HPV and preneoplastic lesions.
Footnotes
Funding: none.
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