Cancer burden and risk factors among women with HIV: a multi-regional study from the D:A:D and RESPOND cohort collaborations

Abstract

Background: Data on cancer incidence and associated risk factors among women with HIV are limited. We investigated cancer burden among women with HIV.

Methods: We included all women ≥18 years from the two large multicentre observational cohort collaborations (D:A:D and RESPOND). The primary outcomes were incidence of all cancers, HPV-related and common individual cancers including breast cancer, lung cancer, and non-Hodgkin lymphoma (NHL) from 2006 to 2021. Baseline was defined as the latest date of entry into local cohort enrolment and 1st January 2006 for D:A:D and 1st January 2012 for RESPOND. Participants were followed from baseline until the date of first cancer, final follow-up or administrative censoring-whichever occurred first. We assessed risk factors using multivariable Poisson regression by applying robust standard errors and determined a population attributable fraction (PAF) for key risk factors for cancers.

Findings: Among 17,512 women included, median age at baseline was 39.5 years (interquartile range, IQR 32.5-46.0). Over 141,404 person-years (PYS) and a median 9.2 (5.5-10.1) years of follow-up, 832 women were diagnosed with any cancer; incidence rate 5.9 (95% CI 5.5-6.4)/1000 PYS, 163 HPV-related cancers (1.1 [1.0-1.3]/1000 PYS), 150 breast cancers (1.1 [0.9-1.2]/1000 PYS), 94 lung cancers (0.7 [0.5-0.8]/1000 PYS) and 72 NHL (0.5 [0.4-0.6]/1000 PYS). Older age (≥45 vs. <45 years), Southern Europe (vs. Western Europe) and smoking were associated with an increased risk of overall cancers. Lower pre-ART nadir CD4, time-updated CD4, and a prior AIDS diagnosis were associated with lung- and HPV-related cancer. In PAF analysis, smoking and HIV-related factors such as lower current CD4, nadir CD4 and HIV viremia significantly contributed to cancer risk.

Interpretation: Our findings suggest that women with HIV older than 45 years, past or current immunosuppressed or current smokers could be candidates for intensified cancer screening and prevention.

Funding: The Highly Active Antiretroviral Therapy Oversight Committee, The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The Brighton HIV Cohort, The National Croatian HIV Cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The Isabel Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort, The University of Cologne HIV Cohort, Merck Life Sciences, ViiV Healthcare, and Gilead Sciences.

Keywords: Cancer incidence; HPV; Modifiable risk factors; Observational cohort study; Women with HIV.

Fig. 1

Cancer incidence among women with HIV in RESPOND and D:A:D among all women with HIV (A) and, stratified by age groups (B) and regions (C). ∗Other gynaecological cancers exclude cervical cancers. HPV-related cancer group included 43 anal, 83 cervical, 28 other non-cervical HPV-related gynaecological cancers (3 vaginal and 25 vulval cancers) and 9 head and neck cancers (all were oropharyngeal cancers). The incidence rate was 5.9 (95% CI: 5.5, 6.4)/1000 PYS for all cancers (n = 832), 1.1 (1.0, 1.3)/1000 PYS for HPV-related cancers (n = 163), 0.7 (0.5, 0.8)/1000 PYS for lung cancer (n = 94), 1.1 (0.9, 1.2)/1000 PYS for breast cancer (n = 149), 0.5 (0.4, 0.6)/1000 PYS for NHL (n = 70), 0.6 (0.5, 0.7)/1000 PYS for cervical cancer (n = 80), 0.3 (0.2, 0.4)/1000 PYS for head and neck cancers (HENE) (n = 46), 0.3 (0.2, 0.4)/1000 PYS for anal cancer (n = 42) and 0.4 (0.3, 0.5)/1000 PYS other gynaecological cancers (n = 59). Abbreviations: HENE, head and neck; NHL, non-Hodgkin lymphoma.

Fig. 2

Forest plot illustrating factors associated all cancers (n = 832). ∗Due to small numbers, USA was combined with Western Europe, Australia was combined with Northern Europe, and Eastern Central Europe combined with Eastern Europe. † Time-updated variables. ‡ Ethnicity was not included in the multivariable model due to large number of missing values. Abbreviations: BMI, body mass index; IDU, injection drug use; HCV, hepatitis C virus; HBV, hepatitis B virus; INSTI, integrase strand transfer inhibitor; PI, protease inhibitor; NNRTI, non-nucleos(t)ide reverse transcriptase inhibitor.

Fig. 3

Forest plot illustrating factors associated HPV-related cancers (n = 163). ∗ Due to small numbers, USA was combined with Western Europe, Australia was combined with Northern Europe, and Eastern Central Europe combined with Eastern Europe. † Time-updated variables. ‡ Ethnicity was not included in the multivariable model due to large number of missing values. Abbreviations: BMI, body mass index; IDU, injection drug use; HCV, hepatitis C virus; HBV, hepatitis B virus; INSTI, integrase strand transfer inhibitor; PI, protease inhibitor; NNRTI, non-nucleos(t)ide reverse transcriptase inhibitor.

Fig. 4

Forest plot illustrating factors associated with breast cancer (n = 150), lung cancer (n = 94) and non-Hodgkin lymphoma (n = 72). ∗ Due to small numbers, USA was combined with Western Europe, Australia was combined with Northern Europe, and Eastern Central Europe combined with Eastern Europe. † Time-updated variables. ‡ Ethnicity was not included in the multivariable model due to large number of missing values. Abbreviations: BMI, body mass index; IDU, injection drug use; HCV, hepatitis C virus; HBV, hepatitis B virus; INSTI, integrase strand transfer inhibitor; PI, protease inhibitor; NNRTI, non-nucleos(t)ide reverse transcriptase inhibitor.

Fig. 5

Population attributable fractions for modifiable risk factors for cancer risk for (A) all cancers, (B) HPV-related cancers, (C), breast cancer, and (D) lung cancer. The population attributable fraction is calculated while accounting for time-varying risk factors. Error bars represent 95% confidence intervals. Abbreviations: BMI, body mass index; AIDS, acquired immune deficiency syndrome; HBV, hepatitis B virus; HCV, hepatitis C virus.