The Trends and Risk Factors of AIDS-Defining Cancers and Non-AIDS-Defining Cancers in Adults Living with and without HIV: A Narrative Review.

The introduction of antiretroviral therapy (ART) has revolutionized HIV infection management, resulting in improved outcomes and survival for people living with HIV (PLWH). However, as PLWH are living longer and aging, non-AIDS-defining cancers (NADCs) represent a significant source of morbidity and mortality in the HIV-infected population. Here, we review the epidemiology of NADCs in PLWH. Cancer mortality among PLWH is much higher than that among the general population. Up to 10% of deaths among PLWH have been attributed to NADCs. Furthermore, PLWH have an increased risk for specific NADCs, including lung cancer, hepatocellular carcinoma, head and neck cancers, anal cancer, and Hodgkin lymphoma. In the past decade, the incidence rates of AIDS-defining cancers (ADCs) have been decreasing while the incidence rates of NADCs have been increasing. In particular, the incidence of specific NADCs are changing at different rates. For example through 2010, the incidence rates for anal, liver, and prostate cancers among PLWH had increased, while incidence rates for lung cancer had decreased and incidence rates for colorectal cancer remained relatively stable over time. However, as early ART becomes more prevalent and the percentage of PLWH over 50 increases, these trends may evolve further. Incidence of NADCs should be expected to increase further as the PLWH population continues to age. Screening and prevention for these cancers among the HIV-infected population should be emphasized.

BackgroundAntiretroviral therapy (ART) restores cellular immunity, significantly reducing AIDS-related mortality and morbidity thus improving the quality of life among People living with HIV (PLHIV). Studies done in several countries show a decline in AIDS defining cancers (ADCs) with the introduction of ART however the increased longevity has led to the increase of Non-AIDS defining cancers (NADCs). The study was aimed at studying the changing spectrum and trends of cancer among Human Immunodeficiency Virus (HIV) patients in southwestern Uganda.MethodsThe study was a retrospective chart review of records of HIV-positive patients attending/receiving care from the Oncology clinic and ISS clinic of Mbarara Regional Referral Hospital (MRRH) who were, diagnosed with cancer for the past 10 years (January 2012–2021). Data were statistically analyzed using STATA version 17 (Stata Corp, Texas, US) at P < 0.05.ResultsMales were more common at 64.5% while the median age was 37 years (IQR 29–47 years). ADCs were seen in 77.5% of the population while participants with NADCs were older (p < 0.001). The majority 73.3% (283/386) were in later stages (3 and 4). Having either ADCs or NADCs was different across HIV stages (p < 0.001). The median baseline CD4 count was 205 cells/μl (IQR: 90–400 cells/μl). The median duration on ART was 15 months (IQR 3–65 months). Participants with ADCs had been on ART for a shorter duration of time (p < 0.001). Only the outcome of patients with ADCs were available. The outcome varied with sex (p < 0.036), baseline CD4 (p < 0.048), and HIV stage (p < 0.002). Males were more likely to die (30/38 or 78.95%) and lost to follow-up (26/41 or 60.98%). Participants with baseline CD4 cell count > 200 cells/μl were more than twice likely to be active in care. The Commonest ADC was Kaposi Sarcoma (KS) while the commonest NADC was Squamous cell carcinoma, Not otherwise specified. Age above 50 years was associated with a significantly reduced risk of ADCs (OR: 0.11; 95% CI: 0.03–0.43; p value: 0.002). The risk of ADCs increased from stage 2 (OR: 0.46, p-value: 0.03; 95% CI: 0.23–0.91) to stage 3 (OR: 1.13; p-value: 0.66; 95% CI: 0.65–1.97) but this was not statistically significant. The risk of ADCs decreased with increasing ART duration (P value < 0.05).ConclusionADCs are still a major health challenge in Southwestern Uganda despite the increasing the coverage and uptake of ART in region. These have mostly affected the young people, people who have been on HAART for a shorter period and those with lower CD4 cell count at initiation of ART.

Cancer risk is higher in people living with HIV (PLWH) compared with the general population, and cancers related to age are expected to be most prevalent. We determined the spectrum and incidence rates of AIDS-defining cancers (ADC) and non-AIDS-defining cancers (NADC) and of lung, Hodgkin lymphoma (HL), head and neck (HNC), colon-rectum, anal, liver, breast, prostate, and urinary bladder cancers between January 2010 and December 2015 in the French Dat'AIDS cohort. Incidence rates were calculated by year and compared using the χ 2 test for linear trend. Standardized incidence ratios [SIR (95% confidence interval)] were calculated relative to the French general population. Among 44,642 patients, corresponding to 180,216.4 person-years (PY), 1,440 cancer cases occurred in 1,314 patients. ADC incidence was 191.4 (172.3-212.7)/105 PY and declined over time overall and in men, whereas NADC incidence was higher [548.8 (515.6-584.1)/105 PY] and did not change. In men, non-Hodgkin lymphoma was the most common cancer, but prostate cancer had the highest incidence among NADCs. Breast cancer was the most common cancer in women. SIRs were higher for cervical cancer [1.93 (1.18-3.14)], HNC in women [2.4 (1.4-4.2)], liver [overall: 3.8 (3.1-4.6); men: 3.2 (2.5-4.0); women: 12.9 (8.3-20.0)], and HL [overall: 13.8 (11.1-17.1); men: 16.2 (12.9-20.4); women: 6.2 (3.22-11.9)] but lower for lung [overall: 0.7 (0.6-0.9); men: 0.7 (0.5-0.8)], prostate [0.6 (0.5-0.7)], and breast cancers [0.6 (0.4-0.7)]. Spectrum of NADCs has changed, with prostate and breast cancers becoming the most common despite their lower SIR. These results confirm the need to maintain regular epidemiologic cancer monitoring in order to update screening guidelines.

Background. Oncological diseases are among the leading causes of death in people living with HIV (PLWH). With the introduction of antiretroviral therapy and the consequent reduction in AIDS-defining cancers (ADC), there has been a growing incidence of non-AIDS-defining cancers (NADC). Methods. A retrospective observational study (cross sectional prevalence analysis) was conducted to investigate the prevalence and spectrum of oncological diseases in patients attending the HIV/AIDS Division at the Ferrara Hospital. The sample included 534 patients evaluated between January 2023 and November 2024 (534/682 met eligibility). Demographic, clinical, and serological data were extracted from medical records. The CDC’s 2014 definition has been adopted for the ADC/NADC classification. Statistical analysis was performed using SPSS version 29 and G*Power 3.1 software. Results. The data analysis revealed 62.8% NADC vs. 37.2% ADC (44 NADCs vs. 26 ADCs). Male individuals and those aged 50 and older were more represented. Patients with ADC more often fell into C2–C3 groups, indicative of severe immunodeficiency, while NADCs were more prevalent in clinical groups A1–B3. Statistical analysis showed that viral load was more frequently under 50 copies/mL in the NADC group, while it tended to be higher in the ADC group. Conclusions. These results align with current scientific evidence regarding the global prevalence of ADCs and NADCs. The findings highlight the need to implement targeted oncological screening strategies for HIV-positive patients to promote early diagnosis and improve prognosis.

Advances in antiretroviral therapy (ART) have normalized the life expectancy of people living with HIV (PLWH) but have been linked to a premature presentation of age-related comorbidities, including cancer. Telomere length (TL) is a marker of cellular aging and was investigated in blood leukocytes from 78 PLWH on ART, compared with 163 HIV-uninfected controls. The PLWH group was stratified into three subgroups: HIV-only (&lt;em&gt;n&lt;/em&gt; = 57), HIV with AIDS-defining cancer (ADC, &lt;em&gt;n&lt;/em&gt; = 9), and HIV with NADC (&lt;em&gt;n&lt;/em&gt; = 12). Quantitative polymerase chain reaction (qPCR) was used to measure the Relative Telomere Length (RTL), expressed as a T/S ratio. The mean RTL was significantly longer in PLWH (&lt;em&gt;p&lt;/em&gt; = 0.0002) and in the HIV/Cancer group (&lt;em&gt;p&lt;/em&gt; = 0.0125) than in the control group (&lt;em&gt;n&lt;/em&gt; = 163). In addition, the mean RTL was significantly longer in the PLWH group with non-AIDS-defining cancers (NADCs) compared to the control group (&lt;em&gt;p&lt;/em&gt; = 0.03). However, no statistical difference between the HIV-only versus the HIV/cancer groups concerning RTL was observed. PLWH with a longer time since diagnosis of HIV infection (&gt;13 years) had a trend towards longer RTL, showing a borderline statistical significance (&lt;em&gt;p&lt;/em&gt; = 0.06). Analysis by cancer type showed ADCs were mainly Kaposi’s sarcoma (44.5%) and cervical cancer (33.3%), while NADCs were most commonly anal cancer (25%) and breast cancer (16.7%). These findings support the thesis that long-term ART may be associated with telomere elongation in PLWH, challenging the general perception of telomere shortening in this population. The significantly longer RTL in the NADC group suggests that telomere elongation confers greater cellular replicative potential, which might contribute to the elevated cancer risk in PLWH.

With a high HIV adult prevalence, the burden of cancer in Botswana has surged over the years, posing a significant threat for people living with HIV (PLWH). While HIV/AIDS-related deaths have declined due to effective antiretroviral therapy (ART), PLWH remain at elevated risk for cancer and related mortality. We aimed to evaluate all-cause mortality after cancer diagnosis among people with and without HIV in Botswana. We included adults aged ≥ 18years who were reported in the national cancer registry between 1990 and 2021. The crude, age-standardized mortality (ASMR) rates per 100,000 and standardized mortality ratios (SMRs) were calculated. We determined time trends using generalized linear regression, assuming a Poisson distribution. Over 30years, 27,726 cancer cases and 9,609 deaths were reported. Of all the deaths, 4,548 (47.3%) were among PLWH, 1,183 (12.3%) among people without HIV, and 3,878 (40.4%) among people with unknown HIV status. Compared with people without HIV, the ASMRs for PLWH were higher and increased significantly from 1990 to 2021 (from 12.5 to 297.9 per 100,000, respectively; p-trend < 0.001) versus people without HIV (from 0.4 to 7.3 per 100,000, respectively; p-trend = 0.006). Further, mortality rates rose among PLWH who had AIDS-defining cancers (ADCs), non-AIDS-defining cancers (NADCs), breast and cervical cancers (p-trend < 0.001). Although the SMRs for all ADCs and most NADCs sub-types declined after ART roll-out, in the late post-ART period, these were in excess among PLWH. Increasing trends and excess mortality among PLWH with cancer suggest a greater need for targeted screening strategies, and the provision of access to timely HIV and cancer treatment.

SummaryBackgroundNon-AIDS-defining cancers (NADCs) are now becoming a rising cause of morbidity among people living with HIV (PLHIV) in the highly active antiretroviral therapy (HAART) era. We conducted a systematic review and meta-analysis to estimate the summary risk of incidence and mortality of a wide range of NADCs among PLHIV compared with the general population.MethodsThis systematic review and meta-analysis was registered in the PROSPERO (registration number CRD42020222020). We searched PubMed, EMBASE, Cochrane library, and Web of Science for relevant studies published before Jan 24, 2022. Cohort or registry linkage studies comparing the incidence or mortality of individual NADCs in PLHIV with that in the general population were included. Studies simply reporting outcomes of cancer precursor lesions or combined NADCs were excluded. We calculated pooled standardised incidence (SIRs) and standardised mortality ratios (SMRs) and their 95% confidence intervals (CIs) using random-effects models, and used robust variance estimation to account for non-independence in study-level effect sizes.FindingsWe identified 92 publications arising from 46 independent studies including 7 articles out of 7 studies from developing countries. Among the 40 types of NADCs investigated, all of the 20 infection-related NADCs, cancers related with human papillomavirus infection in particular, and half of the 20 non-infection-related NADCs occurred in excess in PLHIV compared with the general population. This risk pattern was consistent in most WHO regions and in both high-income and low-and middle-income countries. The increased SIRs for various NADCs were more evident among PLHIV with advanced immunodeficiency, and was explored by HIV transmission route, and use of HAART. PLHIV had increased mortality for anal cancer (SMR 124·07, 95% CI 27·31-563·72), Hodgkin lymphoma (41·03, 2·91−577·88), liver cancer (8·36, 3·86−18·11), lung cancer (3·95, 1·52-10·26), and skin melanoma (3·95, 1·28−12·2).InterpretationPLHIV had increased incidence and mortality for a wide spectrum of NADCs. Primary prevention and effective treatment for NADCs in this population is urgently needed.FundingNatural Science Foundation of China Excellent Young Scientists Fund, Natural Science Foundation of China International/Regional Research Collaboration Project, National Science and Technology Major Project of China, Sanming Project of Medicine in Shenzhen, High Level Project of Medicine in Longhua, Shenzhen, Shenzhen Science and Technology Innovation Commission Basic Research Program, Special Support Plan for High-Level Talents of Guangdong Province, the Guangzhou Basic Research Program on People's Livelihood Science and Technology, the National Natural Science Foundation of China.

The association between antiretroviral therapy adherence following cancer diagnosis and survival outcomes in people living with HIV and cancer in Shanghai, China.

The incidence of non-AIDS-defining cancers (NADCs) in HIV-positive patients has increased over recent years. Most studies of the risk and spectrum of NADCs are primarily based on male populations, and only a few have provided specific information regarding females. We retrospectively analyzed all incident NADCs occurring in a cohort of HIV-positive patients followed up between 1985 and 2011. Incidence rates before and after the introduction of highly active antiretroviral therapy (HAART) were examined using Poisson regression models. Standardized incidence ratios (SIRs) were used to compare the cancer risk of HIV-infected subjects with that of the age- and gender-matched general population as estimated by the Milan Cancer Registry. Five thousand nine hundred twenty-four patients (4382 men and 1542 women) contributed 50,990 person-years to the follow-up. Among them, 144 had new NADC diagnosis. The overall incidence increased from 1.0 case/1000 person-years in the pre-HAART period to 4.5 cases/1000 person-years in the HAART period (P < 0.01). In women, the risks were higher than expected in the case of cancer of the vulva (SIR = 69.2), Hodgkin lymphoma (SIR = 7.5), anal cancer (SIR = 41.2), and lung cancer (SIR = 4.8). In men, the risks were higher than expected in the case of anal cancer (SIR = 91.5), Hodgkin lymphoma (SIR = 13.0), tonsil cancer (SIR = 10.9), lung cancer (SIR = 2.1), and liver cancer (SIR = 7.1). The spectrum and incidence of NADCs in our cohort increased over time. The incidence of NADCs, especially virus- and smoking-associated cancers, was significantly higher than expected in HIV-positive men and women.

BackgroundData on the long-term risks of non-AIDS defining cancers (NADCs) are limited, especially in Asians. The incidence of NADCs may correlate with the epidemiological trend of cancers or oncogenic infection in each country, and thus the target cancers would be different between Western and Asian countries. We aimed to elucidate the incidence of NADCs and its predictive factors in Asian HIV-infected patients.MethodsSubjects were HIV-infected patients (n = 1001) periodically followed-up for 9 years on average. NADCs were diagnosed by histopathology and/ or imaging findings. Standardized incidence ratios (SIR) were calculated as the ratio of the observed to expected number of NADCs for comparison with an age-and sex-matched general population. Cox’s proportional hazards model was used to estimate hazard ratios (HR).ResultsDuring the median follow-up of 9 years, the 10-year cumulative incidence of NADCs was 6.4%.At NADC diagnosis, half of patients presented at age 40–59 years and with advanced tumor stage. Compared with the age-and sex-matched general population, HIV-infected patients are at increased risk for liver cancer (SIR, 4.7), colon cancer (SIR, 2.1), and stomach cancer (SIR, 1.8). In multivariate analysis, a predictive model for NADCs was developed that included age group (40–49, 50–59, 60–69, and ≥ 70 years), smoker, HIV infection through blood transmission, and injection drug use (IDU), and HBV co-infection. The c-statistic for the NADCs predictive model was 0.8 (95%CI, 0.8–0.9, P < 0.001). The higher 10-year incidence rate of NADCs was associated with increasing prediction score.ConclusionsLiver and colon cancer risk was elevated in Asian HIV-infected individuals, similar to in Western populations, whereas stomach cancer risk was characteristically elevated in Asian populations. Half of Asian NADC patients were aged 40–59 years and had advanced-stage disease at diagnosis. Periodic cancer screening may be warranted for high-risk subpopulations with smoking habit, HIV infection through blood transmission or IDU, and HBV co-infection, and screening should be started over 40 years of age.

Background:People living with HIV (PLWH) are at increased risk for frailty-related fracture. Limited evidence suggests recent diagnosis of non-AIDS defining cancer (NADC) is a risk factor for fracture among PLWH. We evaluated frailty-related fracture by HIV and cancer status to inform the burden of fracture among PLWH.Methods:We included 14,554,711 beneficiaries without HIV and 159,188 beneficiaries with HIV who were 30–64 years old enrolled in Medicaid between 2001–2015 in 14 states. HIV, NADC, and fracture diagnoses were identified from inpatient and other non-prescription claims. We calculated age-specific fracture incidence per 100 person-years and 95% confidence intervals for beneficiaries with no NADC or HIV, NADC only, HIV only, or both. We estimated the cumulative incidence of frailty-related fracture with death as a competing event for each group.Results:Fracture incidence increased with age in all groups. Compared to beneficiaries without NADC or HIV, all groups had significantly higher age-specific incidence of fracture. Beneficiaries with HIV and NADC had higher incidence of frailty-related fracture than those with HIV only at all ages (Incidence per 100 person-years for ages 30–44 Both: 1.24 95%CI:0.96,1.59; HIV: 0.74 95%CI:0.71,0.77; for ages 60–64 Both: 2.11 95%CI:1.64,2.67; HIV: 1.47 95%CI:1.37,1.58). Conversely, cumulative incidence was lowest for both HIV and NADC, likely due to in part to the very high incidence of death.Conclusion:Beneficiaries with HIV and NADC had higher age-specific frailty-related fracture and death than beneficiaries with HIV alone. Future work should investigate fracture risk among PLWH with cancer to inform interventions for fracture prevention.

To determine incidence of non-AIDS-defining cancers (NADC) in HIV-infected patients before (P1) and during (P2) the use of highly active antiretroviral therapy (HAART) relative to that observed in the French general population (FGP) of the same age and sex. Sex- and age-adjusted NADC standardized incidence ratios (SIR), with FGP as reference, were estimated in 1992 to 1995 (P1) and in 1996 to 1999 (P2) in a French Hospital Database on HIV prospective hospital cohort study. NADCs were diagnosed in 260 patients during P1 and 391 patients during P2 among the 77,025 patients included in the database between January 1, 1992, and December 31, 1999. Estimated incidence of all cancers was higher in HIV-infected men than in FGP during both periods (P1 SIR = 2.36 and P2 SIR = 1.91). No excess of cancers was observed among HIV-infected women in either period. Incidence of all cancers did not change from P1 to P2 in either sex (SIR = 0.96 for men and 1.00 for women). In contrast, incidence of Hodgkin's disease (HD) was higher than in FGP in both sexes and both periods and increased in P2 as compared with P1; incidence of lung cancer was higher in both sexes during P2. Relative to FGP, the overall incidence of NADCs was increased in HIV-infected men but not in women and did not differ between P1 and P2. Only HD was much more common in HIV infection, and the potential role of HAART on HD cannot be excluded.

HIV contributes significantly to the global burden of cancer. In developing countries, AIDS-defining cancers predominate due to inconsistent access to antiretroviral therapy (ART). Even though AIDS-defining cancers are now less common in developed countries, the prevalence of non-AIDS-defining cancers (NADCs) has increased due to longer life expectancy in a milieu of chronic immune activation, exposure to oncogenic viruses, lifestyle factors, and environmental variables. In resource-constrained countries with inconsistent access to ART, Kaposi sarcoma, aggressive B-cell lymphomas, and cervical cancer continue to be a large problem. Not only do people living with HIV (PLWH) face higher cancer incidence and mortality, but they also encounter persistent stigmatization and barriers to equitable access to cancer treatment. To bridge this gap, the United States National Cancer Institute (NCI) established the AIDS Malignancy Consortium (AMC) to evaluate novel treatments, preventive strategies, and clinical guidelines for PLWH by conducting both domestic and international research. The AMC also emphasizes the development of robust research infrastructure in resource-limited countries, training of researchers, and fair management of clinical trial specimens. Despite various challenges, the AMC has contributed significant insights to international cancer trials among PLWH, thereby transforming clinical practice in low-resource areas. The high global burden of HIV-associated cancer underscores the need for comprehensive research, improved healthcare access, and greater inclusion of PLWH in cancer clinical trials.

IntroductionNon-Hodgkin’s Lymphoma (NHL), Kaposi’s sarcoma and invasive carcinoma of cervix are AIDS defining cancers (ADCs) seen in people living with HIV (PLHIV). After the introduction of combination antiretroviral therapy (cART)...

Identifying strategies to further reduce AIDS-related mortality requires accurate estimates of the extent to which mortality among people living with HIV (PLHIV) is due to AIDS-related or non-AIDS-related causes. Existing approaches to estimating AIDS-related mortality have quantified AIDS-related mortality as total mortality among PLHIV in excess of age- and sex-matched mortality in populations without HIV. However, recent evidence suggests that, with high antiretroviral therapy (ART) coverage, a growing proportion of excess mortality among PLHIV is non-AIDS-related. We searched Embase on 22/09/2023 for English language studies that contained data on AIDS-related mortality rates among adult PLHIV and age-matched comparator all-cause mortality rates among people without HIV. We extracted data on the number and rates of all-cause and AIDS-related deaths, demographics, ART use and AIDS-related mortality definitions. We calculated the proportion of excess mortality among PLHIV that is AIDS-related. The proportion of excess mortality due to AIDS was pooled using random-effects meta-analysis. Of 4485 studies identified by the initial search, eight were eligible, all from high-income settings: five from Europe, one from Canada, one from Japan and one from South Korea. No studies reported on mortality among only untreated PLHIV. One study included only PLHIV on ART. In all studies, most PLHIV were on ART by the end of follow-up. Overall, 1,331,742 person-years and 17,471 deaths were included from PLHIV, a mortality rate of 13.1 per 1000 person-years. Of these deaths, 7721 (44%) were AIDS-related, an overall AIDS-related mortality rate of 5.8 per 1000 person-years. The mean overall mortality rate among the general population was 2.8 (95% CI: 1.8-4.0) per 1000 person-years. The meta-analysed percentage of excess mortality that was AIDS-related was 53% (95% CI: 45-61%); 52% (43-60%) in Western and Central Europe and North America, and 71% (69-74%) in the Asia-Pacific region. Although we searched all regions, we only found eligible studies from high-income countries, mostly European, so, the generalizability of these results to other regions and epidemic settings is unknown. Around half of the excess mortality among PLHIV in high-income regions was non-AIDS-related. An emphasis on preventing and treating comorbidities linked to non-AIDS mortality among PLHIV is required.