A team of scientists, led by the University of Bern, Switzerland, and in collaboration with the Universities of Cape Town and Stellenbosch, has found a link between a higher cervical cancer risk and lower CD4 counts among HIV+ women, reports Medscape.
Both lower CD4 counts and higher HIV RNA viral load were associated with higher incidence rates of moderate and severe cervical dysplasia, carcinoma in situ, and invasive cervical cancer; the positive association between HIV RNA viral load and pre-cancer and cancer rates largely attenuated after adjustment for CD4 count, they said.
The researchers had analysed medical claims data from South Africa’s national HIV disease management programme to examine whether earlier and recent measures of CD4 counts, and HIV RNA viral load were tied to the incidence of cervical pre-cancer and invasive cervical cancer.
The analysis included 66 920 women with HIV infection (median age, 34.8 years) enrolled in the programme between January 2011 and December 2022, and assessed four outcomes based on International Classification of Diseases, 10th Revision (ICD-10) codes: moderate cervical dysplasia, severe cervical dysplasia, cervical carcinoma in situ, and cervical cancer.
They used Cox proportional hazards models to assess associations of CD4 counts and HIV RNA viral load with these outcomes; the models were adjusted for age, calendar year, and antiretroviral therapy (ART) initiation.
Incidence rates per 100 000 person-years were 394 (95% CI, 372-417) for moderate cervical dysplasia, 405 (95% CI, 383-428) for severe cervical dysplasia, 66 (95% CI, 58-76) for cervical carcinoma in situ, and 70 (95% CI, 61-79) for cervical cancer.
Among women with HIV infection, those with lower CD4 counts (< 50 cells/μL) had a nearly fivefold higher risk for cervical carcinoma in situ (adjusted hazard ratio [aHR], 4.84; 95% CI, 2.40-9.79) and a more than fivefold higher risk for cervical cancer (aHR, 5.38; 95% CI, 2.54-11.43) than those with higher CD4 counts (≥ 500 cells/μL).
The lowest CD4 count within 30 months was associated with a higher risk for moderate cervical dysplasia (aHR, 2.53; 95% CI, 1.86-3.43) and severe cervical dysplasia (aHR, 2.67; 95% CI, 1.96-3.62).
Higher HIV RNA viral load categories (< 50; 50-999; 1000-99,999; and > 100,000 copies/mL) showed positive associations with pre-cancer and cancer rates in models unadjusted for CD4 count, but these associations were attenuated after adjustment for CD4 count.
“Sustaining high CD4 counts through early ART initiation and effective HIV management, combined with the use of CD4 counts for risk stratification in cervical screening, may help improve cervical cancer prevention among WWH [women with HIV infection] in South Africa,” the authors wrote.
The study, which was led by Yann Ruffieux, University of Bern, and published online in Clinical Infectious Diseases, had some limitations.
The data were derived from a private HIV disease management programme, and therefore, the study may not have been generalisable to women with HIV infection in South Africa’s public sector.
Outcome ascertainment relied on ICD-10 codes from insurance claims, which are prone to misclassification and lack the granularity of full histopathology reports.
The study also lacked information on important behavioural and clinical covariates, including dates of ART initiation, human papillomavirus vaccination, and cervical screening, which are known to influence the risk for cervical cancer and could have confounded some of the observed associations.
Study details
Association of immunodeficiency and human immunodeficiency virus viremia with cervical pre-cancer and cancer risk among women with HIV in South Africa
Yann Ruffieux, John Andoh, Andreas Haas et al.
Published in Clinical Infectious Diseases on 14 February 2026
Abstract
Background
Women with human immunodeficiency virus-1 (HIV) (WWH) have a higher cervical cancer risk than women without HIV. The timing and extent to which HIV viremia and immunodeficiency contribute to cervical carcinogenesis remain incompletely understood.
Methods
We conducted a cohort study using medical claims data from a South African HIV programme (2011–2022) and calculated incidence rates of cervical pre-cancer and cancer. Cox proportional hazards models assessed associations with CD4 cell count and HIV ribonucleic acid (RNA). We tested summary and point-in-time CD4 and HIV RNA measures with 6–36 months’ lag periods. Models were adjusted for age, calendar year, and antiretroviral therapy (ART) initiation; fully adjusted models included both CD4 count and HIV RNA.
Results
More than 66 000 WWH contributed more than 300 000 person-years; 1202 WWH developed moderate dysplasia (incidence rate: 394/100 000 person-years), 1237 severe dysplasia (405/100 000 person-years), 211 carcinoma in situ (66/100 000 person-years), and 257 cervical cancer (70/100 000 person-years). Lower CD4 counts were strongly associated with higher rates of cervical dysplasia, carcinoma in situ, and cancer, independent of HIV RNA. Lowest CD4 count over 30 months was the most informative measure for cervical dysplasia while CD4 count lagged by 24 months was most informative for cervical cancer. Higher HIV RNA was associated with increased risk of pre-cancer and cancer in models unadjusted for CD4 count, with associations attenuated after adjustment.
Conclusions
Maintaining high CD4 counts and achieving viral suppression through early ART initiation, along with using CD4 cell count for risk stratification in cervical screening, may help improve cervical cancer prevention among WWH in South Africa.
Clinical Infectious Diseases article – Association of immunodeficiency and human immunodeficiency virus viremia with cervical pre-cancer and cancer risk among women with HIV in South Africa (Open access)
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciag093/8483304?login=false
Medscape article – Low CD4 Count Tied to Cervical Cancer Risk in HIV Infection (Open access)
See more from MedicalBrief archives:
High rates of cervical cancer found in women living with HIV
Invasive cervical cancer rates high in women living with HIV in Africa and Latin America
Almost 40% of cancers tied to modifiable risk factors – global report