Prevalence and factors associated with high-risk oncogenic human papillomavirus infection among women living with HIV in Kinshasa, the Democratic Republic of the Congo

This cross-sectional study of 436 women living with HIV in Kinshasa reveals a 47.25% prevalence of high-risk oncogenic HPV infection, which is significantly associated with advanced HIV clinical stage, high viral loads, and shorter duration of antiretroviral therapy, highlighting the urgent need to integrate systematic HPV screening into HIV care programs.

The Gist

The Big Picture: A Double Trouble Situation

Imagine your body is a fortress. HIV is like a group of saboteurs that has managed to break into the fortress walls, weakening the security guards (your immune system). HPV (Human Papillomavirus) is like a stealthy thief that tries to sneak in through the back door.

When the security guards are strong, they usually catch the thief. But when HIV has weakened the guards, the thief (HPV) can stay inside for a long time. If the thief stays too long, they can start building dangerous structures that turn into cervical cancer.

This study looked at women in Kinshasa, Democratic Republic of the Congo, who are living with HIV. The researchers wanted to know: How many of these women have this "stealth thief" (HPV) inside them, and what makes it easier for the thief to stay?

The Main Findings: The Numbers

The researchers checked 436 women. Here is what they found:

• The "Half-and-Half" Rule: Nearly one out of every two women (47%) tested positive for the dangerous, cancer-causing type of HPV. That's a very high number compared to the general population.
• The "Big Two" vs. The "Rest": Most people know about HPV types 16 and 18 because they are the most famous villains. The study found that about one in four women had these specific types. However, the other three-quarters of the infections were caused by other dangerous types of HPV that are less talked about but just as risky.
  • Analogy: It's like a bank robbery. Everyone knows about the two famous robbers (Types 16 & 18), but in this city, there's a whole gang of other robbers (the other types) causing just as much trouble.

The Clues: What Makes the Problem Worse?

The researchers acted like detectives, looking for clues on what makes a woman more likely to have this infection. They found three main "risk factors":

1. The Weakened Fortress (Advanced HIV):
   Women whose HIV disease had progressed to a later stage (Stage 3 or 4) were much more likely to have HPV.

   • Analogy: When the fortress walls are crumbling (advanced HIV), it's much easier for the thief to sneak in and hide.

2. The Uncontrolled Engine (High Viral Load):
   Women whose HIV was actively multiplying in their blood (high viral load) were three times more likely to have HPV.

   • Analogy: Think of the HIV virus as a car engine revving too high. If the engine is roaring (high viral load), the car is out of control, and the security guards are too busy fighting the engine noise to notice the thief.

3. The New Guard (Short Treatment Time):
   Women who had only been on HIV medication (antiretroviral therapy) for less than two years were at higher risk.

   • Analogy: If you just hired new security guards, it takes them a while to get trained and strong. Once they've been on the job for a while (more than 2 years), they do a better job of keeping the thief out.

What Does This Mean for the Future?

The study concludes that we need to change how we protect these women.

• Don't Just Look, Test: Instead of just looking at the cervix with a vinegar solution (a common, older method), doctors should use a "molecular scanner" (DNA test) to find the thief's DNA directly. This is like using a metal detector instead of just looking for footprints.
• Fix the Fortress First: The best way to stop the thief is to fix the fortress walls. Keeping HIV under control with medication is the best defense against HPV.
• Vaccinate: Since there are so many different types of "thieves" (HPV strains) in this region, the current vaccines might not catch them all. The researchers suggest we need better vaccines and screening programs specifically designed for women living with HIV in Africa.

The Takeaway

In simple terms: Women living with HIV in Kinshasa are facing a very high risk of a dangerous virus that causes cancer. The risk is highest when their HIV isn't well-controlled or when they haven't been on medication for long. The solution is better testing, keeping HIV under control, and getting vaccinated.

Technical Summary

1. Problem Statement

Cervical cancer (CC) is a leading cause of cancer mortality among women globally, particularly in low- and middle-income countries (LMICs). It is an AIDS-defining illness, and women living with HIV (WLWH) face a significantly elevated risk (six times higher) of developing CC compared to HIV-negative women due to HIV-induced immunosuppression. While High-risk oncogenic Human Papillomavirus (Hr-HPV) is the primary etiological agent, data regarding the specific prevalence and risk factors of Hr-HPV among WLWH in Kinshasa, DRC, were previously lacking. Existing data for the general female population in Kinshasa showed a prevalence of ~24.4%, but the burden within the HIV-positive cohort remained undocumented.

2. Methodology

• Study Design: Observational cross-sectional study conducted from April 2022 to April 2023.
• Setting: DREAM Centre in Kinshasa, a specialized facility for HIV care.
• Population: 436 WLWH aged 25–65 years receiving antiretroviral therapy (ART).
  • Exclusion Criteria: Pregnancy, active menstruation, history of hysterectomy, prior HPV testing, or prior HPV vaccination.
• Data Collection:
  • Clinical/Biological: Sociodemographic data, reproductive history, WHO clinical stage, ART duration, and HIV viral load (VL) were extracted from records or collected via questionnaire.
  • Sample Collection: Cervical samples were collected using the Abbott Cervi-Collect™ kit.
  • Laboratory Analysis: Samples were analyzed using the Abbott RealTime High Risk HPV assay on the m2000 platform. This qualitative real-time PCR detects 14 Hr-HPV genotypes, with specific identification of HPV-16 and HPV-18, and pooled detection of 12 other high-risk types (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68).
• Statistical Analysis:
  • Prevalence calculated with 95% Confidence Intervals (CI).
  • Associations assessed using univariate and multivariate logistic regression.
  • Variables with $p < 0.2$ in univariate analysis or known clinical relevance were included in the multivariate model.
  • Significance threshold: $p < 0.05$.

3. Key Results

• Overall Prevalence: The prevalence of Hr-HPV infection among WLWH in Kinshasa was 47.25% (206/436; 95% CI: 42.58–51.96).
• Genotype Distribution:
  • HPV-16 and/or HPV-18: Detected in 23.79% of participants (approx. 1 in 4 of the total cohort).
  • Other Hr-HPV: The majority of infections (76.21%) were attributed to high-risk genotypes other than 16 and 18.
  • Coinfection: Simultaneous detection of HPV-16, HPV-18, and other genotypes was rare (0.49%).
• Associated Risk Factors (Multivariate Analysis):
  Three factors were significantly associated with Hr-HPV infection after adjustment:
  1. Advanced HIV Clinical Stage: WHO Clinical Stage 3–4 was associated with a 1.75-fold increased risk compared to Stages 1–2 (aOR 1.75; 95% CI 1.16–2.64; $p=0.008$).
  2. High Viral Load: A viral load $\ge$ 1000 copies/mL was strongly associated with infection (aOR 3.08; 95% CI 1.28–7.42; $p=0.012$).
  3. Short ART Duration: Treatment duration of < 2 years was associated with higher risk compared to longer duration (aOR 0.52 for $\ge$ 2 years, indicating a protective effect of longer treatment; $p=0.028$).
• Non-Significant Factors: Age, education level, marital status, number of sexual partners, and BMI did not show statistically significant associations in the multivariate model.

4. Key Contributions

• First Localized Data: Provides the first robust estimate of Hr-HPV prevalence specifically for WLWH in Kinshasa, revealing a rate nearly double that of the general population in the same city.
• Genotypic Profiling: Highlights that while HPV-16/18 are present, a significant proportion of infections involve other high-risk genotypes, suggesting that vaccines targeting only 16/18 may offer incomplete protection for this specific high-risk cohort.
• Clinical Correlations: Establishes a clear link between uncontrolled HIV replication (high VL), advanced immunosuppression (Stage 3/4), and Hr-HPV persistence, reinforcing the importance of viral suppression in preventing cervical precursors.

5. Significance and Implications

• Screening Policy: The findings support the WHO's 2021 guidelines recommending HPV DNA testing as the primary screening method for WLWH. Given the 47% prevalence, systematic screening is critical.
• Vaccination Strategy: The high prevalence of non-16/18 genotypes (76.21%) underscores the need for broader vaccine coverage (e.g., 9-valent vaccines) and the necessity of integrating HPV vaccination into national immunization programs in the DRC.
• Integrated Care: The study advocates for integrating Hr-HPV screening directly into HIV care programs. Women with advanced clinical stages or persistent viremia require intensified monitoring and management.
• Treatment Adherence: The protective effect of ART duration >2 years reinforces the importance of treatment adherence to achieve viral suppression, which serves as a secondary prevention mechanism against HPV-related malignancies.

Limitations

• Cross-Sectional Design: Causality cannot be definitively established.
• Missing CD4 Data: The study relied on WHO clinical staging and viral load but lacked CD4 count data, which is a direct measure of immunosuppression.
• Pooled Genotyping: The 12 non-16/18 genotypes were analyzed as a pooled group, preventing specific analysis of individual non-16/18 strains (e.g., HPV-35, which is prevalent in Africa).