The Lancet HIV

No woman left behind: achieving cervical cancer elimination among women living with HIV

Cervical cancer is the fourth most common malignancy in women of reproductive age globally. The burden of this disease is highest in low-income and middle-income countries, especially among women living with HIV. In 2018, WHO launched a global strategy to accelerate cervical cancer elimination through rapid scale-up of prophylactic vaccination, cervical screening, and treatment of precancers and cancers. This initiative was key in raising a call for action to address the stark global disparities in cervical cancer burden. However, achieving elimination of cervical cancer among women with HIV requires consideration of biological and social issues affecting this population. This Position Paper shows specific challenges and uncertainties on the way to cervical cancer elimination for women living with HIV and highlights the scarcity of evidence for the effect of interventions in this population. We argue that reaching equity of outcomes for women with HIV will require substantial advances in approaches to HPV vaccination and improved understanding of the long-term effectiveness of HPV vaccines in settings with high HIV burden cervical cancer, just as HIV, is affected by social and structural factors such as poverty, stigma, and gender discrimination, that place the elimination strategy at risk. Global efforts must, therefore, be galvanised to ensure women living with HIV have optimised interventions, given their substantial risk of this preventable malignancy.

Cancer risk in adolescents and young adults living with HIV in South Africa: a nationwide cohort study

Literature on cancer in adolescents and young adults (AYA; aged 15-24 years) living with HIV is scarce. We studied cancer incidence in AYA living with HIV in South Africa between 2004 and 2014. In this nationwide cohort study, we included individuals between 15 and 24 years old who had at least two HIV-related laboratory measurements on separate days between Jan 1, 2004, and Dec 31, 2014, recorded in the National Health Laboratory Service database. We used privacy-preserving probabilistic record linkage methods to identify HIV-related laboratory records that most likely belonged to the same individual and to then link these individuals to cancer diagnoses from the National Cancer Registry. We computed incidence rates for the most common cancers in AYA living with HIV, and we assessed associations between these cancers and sex, age, calendar year, and CD4 cell count using Cox proportional hazards models and adjusted hazard ratios (aHRs). We included 782 454 AYA living with HIV (698 066 [89·2%] women) with 1 428 114 person-years of follow-up. Of those, 867 developed incident cancer (incidence rate 60·7 per 100 000 person-years), including 429 who developed Kaposi sarcoma (30·0 per 100 000 person-years), 107 non-Hodgkin lymphoma (7·5 per 100 000 person-years), 48 Hodgkin lymphoma (3·4 per 100 000 person-years), 45 cervical cancer (3·4 per 100 000 woman-years), and 32 leukaemia (2·2 per 100 000 person-years). Kaposi sarcoma was more common in the 20-24 year age group than the 15-19 year age group (aHR 1·39, 95% CI 1·03-1·86). Male sex was associated with higher rates of Kaposi sarcoma (2·06, 1·61-2·63), non-Hodgkin lymphoma (3·17, 2·06-4·89), Hodgkin lymphoma (4·83, 2·61-8·93), and leukaemia (unadjusted HR 5·90, 95% CI 2·87-12·12). Cancer rates decreased over the study period, driven by declining Kaposi sarcoma rates. Lower baseline CD4 cell counts were associated with higher rates of Kaposi sarcoma, cervical cancer, non-Hodgkin lymphoma, and Hodgkin lymphoma, but not leukaemia. Infection-related cancers were the most common cancer types in AYA living with HIV in South Africa, and their incidence rates increased with lower CD4 cell counts. Therefore, innovative strategies to maintaining high CD4 cell counts are needed to reduce the cancer burden in this vulnerable population. US National Institutes of Health and Swiss National Science Foundation.

Prevention and control of HPV-related cancers in people living with HIV

The advent of effective antiretroviral therapy (ART) has increased the lifespan of many people living with HIV. As a result, cancers driven by high-risk human papillomavirus (HPV) infection have emerged as an increasingly important cause of mortality in this population. The complex interplay between HIV and HPV necessitates a deep understanding of the HPV-related cancer burden in people living with HIV and the integration of effective prevention strategies into their care. Although cervical cancer is a global concern, anal cancer is more important among people living with HIV in settings where HIV is more concentrated among men who have sex with men. High HPV prevalence, coupled with resource constraints, particularly in sub-Saharan Africa, where the majority of people living with HIV reside, creates substantial barriers to successful prevention and management of HPV-related malignancies. Implementing preventive measures, such as HPV vaccination and comprehensive screening programmes, is crucial and will require addressing existing health inequities and developing tailored interventions for people living with HIV. The development of enhanced secondary prevention tools and innovative treatment modalities is essential to mitigate the burden of HPV-associated cancers and improve the overall health outcomes for this vulnerable population.

Age-specific distribution of cervical precancer and cancer among women living with HIV across seven countries: a systematic review and an individual patient data meta-analysis

Women living with HIV have an elevated risk for cervical cancer, present earlier, and have more recurrent human papillomavirus (HPV) infections compared with women without HIV. To update WHO recommendations on screening and treatment to prevent cervical cancer, we aimed to identify whether women living with HIV should be screened for cervical cancer at a specific age, the optimal screening interval following a negative cervical screen, and the screening interval following treatment. We conducted a systematic literature review on cervical cancer and HIV by searching MEDLINE, Embase, CENTRAL, the Cochrane Library, and clinical trial registries covering Jan 1, 2012, through to Oct 13, 2019, updating a previous systematic review covering database inception to July, 2012. Included articles reported original data and assessed one or more outcomes related to cervical precancer and cancer in women living with HIV; no restrictions on study design or setting were made. Articles were excluded if they did not include any women living with HIV, or if they reported only HPV genotype prevalence without any other relevant data. Two authors extracted data from any study reporting cervical cancer screening tests and histopathologically confirmed disease outcomes, by age. We analysed summary data on optimal age and screening intervals, providing pooled estimates when possible; we then conducted an individual patient data meta-analysis (IPDMA) to analyse age-specific data on cervical cancer and precancer. Authors of studies with 40 or more women living with HIV and cervical intraepithelial neoplasia (CIN) grade 2+ were invited to submit individual patient data for meta-analysis. Random-effects models were used to calculate predicted probabilities for cervical cancer screening results by age, HIV status, and antiretroviral therapy (ART) status. Of the 304 full-text articles screened, 34 studies from 12 countries, with 128 732 women, including 63 790 women living with HIV, were included in the systematic review. Of 55 studies potentially eligible for the IPDMA, eight studies provided data for 72 350 women, 12 527 of whom were living with HIV, from seven countries (Burkina Faso, Cameroon, India, Kenya, South Africa, Thailand, and the USA). In the IPDMA, the pooled predicted probability of CIN2 or CIN3 among women living with HIV increased from 6·0% (95% CI 0·74-64·1) for ages 15-19 years to 32·4% (8·3-72·7) for ages 20-24 years, 42·1% (16·4-80·2) for ages 25-29 years, 50·3% (16·3-80·0) for ages 30-34 years, 47·0% (16·3-80·0) for ages 35-39 years, 49·0% (16·3-80·2) for ages 40-44 years, 58·1% (17·0-81·5) for ages 45-49 years, and 55·3% (21·0-86·6) for age 50 years and older; invasive cervical cancer was uncommon before 30 years of age. In the systematic review, women living with HIV who had a negative baseline cytology result and negative HPV test had a cumulative incidence of developing CIN2+ that ranged from 0·8% to 5% within 4·2-6·4 years and a cumulative incidence of developing of CIN of any grade up to 10% within 12 years. Also in the systematic review, women living with HIV had high recurrence of CIN2+ following treatment (11-27% by 1 year follow-up, 3-64% by 3 years, and 57% by 10 years). No significant evidence of publication bias was found in the data included in the IPDMA (Egger's test p=0·83). Our data show a clear, age-related increase in CIN2 and CIN3 among women living with HIV, with the highest risk occurring in the 45-49-year age group. Our findings informed WHO recommendations to initiate cervical cancer screening for women living with HIV at age 25 years, with regular screening every 3-5 years. Expanding screening and treatment is necessary to reduce cervical cancer incidence towards its elimination. US Agency for International Development and US President's Emergency Plan for AIDS Relief.