Mapping the HPV Landscape in South African Women: A Systematic Review and Meta-Analysis of Viral Genotypes, Microbiota, and Immune Signals

Abstract

This systematic review and meta-analysis evaluate human papillomavirus (HPV) prevalence, genotype distribution, and associations with cervicovaginal microbiota and cytokine profiles among South African women, where cervical cancer ranks as the second most common cancer. PubMed, SCOPUS, and Web of Science were searched for studies on HPV infection up to 21 September 2024. The pooled prevalence was estimated using a random-effects model, with subgroup analyses by province, sample type, and HIV status. Publication bias was evaluated using funnel plots and Egger's test. Of the 19,765 studies screened, 120 met the inclusion criteria, comprising 83,266 participants. Results indicate a high HPV burden, with a pooled prevalence of 58% (95% CI: 52-64%), varying regionally from 53% (95% CI: 41-65%) to 64% (95% CI: 55-73%), with some regions under-researched. Cervical samples had the highest HPV prevalence (60% (95% CI: 54-66%)), while non-genital samples were less studied. High-risk (HR) HPV types, notably HPV 16 (7.5%), HPV 35 (4.1%), and HPV 18 (3.9%), were prominent, with HPV 35 emphasizing the need for expanded vaccine coverage. HIV-positive women had a higher pooled HPV prevalence (63% (95% CI: 55-71%)). Funnel plot analysis and Egger's test suggested a potential publication bias (p = 0.047). HPV-positive women exhibited lower Lactobacillus levels and an increase in Bacterial Vaginosis (BV)-associated species like Gardnerella, potentially supporting HPV persistence. Cytokine analysis showed elevated MIP-1α and MIP-1β in HPV infections, though cytokine profiles may depend on HPV genotypes. These findings underscore the need for research on HPV-microbiome-immune interactions and call for comprehensive HPV-prevention strategies, including vaccines targeting regional HPV types and tailored interventions for HIV-positive populations.

Keywords: cervical cancer; cervicovaginal microbiota; cytokines; genotype; human papillomavirus (HPV); prevalence.

Figure 1

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram for studies on the prevalence and distribution of HPV types and their interaction with cervicovaginal microbiota and cytokine profile among women living in South Africa.

Figure 2

Forest plot showing the overall prevalence of HPV in South African women based on various studies. The random effects model estimated a pooled prevalence of 58% (95% CI: 52–64%). Significant heterogeneity was observed among the included studies (I² = 99.1%, τ² = 0.9489, p < 0.001).

Figure 3

Geographic distribution of sample types used in HPV studies across South African provinces. The map illustrates the geographic distribution of various sample types used in HPV studies across South Africa. Each dot represents an individual study, and the colour of the dots indicates the sample type: pink for cervical, green for vaginal, yellow for oral, red for anal, blue for breast tissue, brown for cervical and oral, black for laryngeal, turquoise for cervical and blood, and purple for biopsy. The position of each dot within a province does not necessarily reflect the exact location of the study within that province. The map highlights key regions, such as Gauteng and the Western Cape, where HPV research has been most prominent. The Gauteng province, located in the top-right corner, is zoomed out to ensure all sample dots are visible.

Figure 4

Overall prevalence (%) of HR-HPV genotypes detected in studies conducted from 1989 to 2024.

Figure 5

Detection trends of HPV types 16, 18, 35, and 52 from 2005 to 2024. The graphs show the percentage detection of each type over time from all the studies included. Peaks in detection for HPV-16 and HPV-18 are observed from 2005 to 2024, while HPV-35 and 52 show variable detection trends across the years.

Figure 6

Overall prevalence (%) of LR-HPV genotypes detected in studies conducted from 1996 to 2023.

Figure 7

Distribution and prevalence of HR-HPV genotypes among HIV-negative (A) and HIV-positive (B) women. The pie charts represent the percentage prevalence of each HR-HPV genotype within each group.

Figure 8

Distribution of LR-HPV genotypes among HIV-negative (A) and HIV-positive (B) women. The pie charts represent the percentage prevalence of each LR-HPV genotype within each group.

Figure 9

Network analysis of cervicovaginal microbiota composition correlated with HPV infection status. Negative correlations are displayed in blue, while positive correlations are in red. Bacterial species associated with bacterial vaginosis (BV) are shown in purple, Lactobacillus-dominated species are in green, and those bacterial species with association not clearly indicated are shown in black. Taxonomic clusters indicate groups of taxa sharing the same hierarchical classification levels, denoting biological relatedness. Bacterial taxa significantly associated with each HPV category are marked with an asterisk above the species name.

Figure 10

Venn diagrams illustrating elevated cytokine concentrations in women with HPV infection, HIV infection, and bacterial vaginosis (BV) and lowered cytokines in HPV-negative women. The cytokines significantly associated with each category are indicated by the asterisk.