Risk of hepatocellular carcinoma in people with HIV in the United States, 2001-2019.

BACKGROUND: People with HIV have higher risk of hepatocellular carcinoma than the general population, partly because of higher prevalence of coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV). METHODS: We calculated standardized incidence ratios for hepatocellular carcinoma in people with HIV by comparing rates from people with HIV in the HIV/AIDS Cancer Match Study, a population-based HIV and cancer registry linkage, to those in the general population. We used multivariable Poisson regression to estimate adjusted incidence rate ratios among people with HIV and linked the Texas HIV registry with medical claims data to estimate adjusted odds ratios (AORs) of HBV and HCV in hepatocellular carcinoma patients with logistic regression. RESULTS: Compared with the general population, hepatocellular carcinoma rates in people with HIV were elevated 2.79-fold (n = 1736; 95% confidence interval [CI] = 2.66 to 2.92). Hepatocellular carcinoma rates decreased statistically significantly from 2001-2004 to 2015-2019 (P < .001). Compared with men who have sex with men, hepatocellular carcinoma risk was elevated 4.28-fold among men who injected drugs (95% CI = 3.72 to 4.93) and 1.83-fold among women who injected drugs (95% CI = 1.49 to 2.26). In Texas, 146 hepatocellular carcinoma cases among people with HIV were linked to claims data: 25% HBV positive, 59% HCV positive, and 13% coinfected with HBV and HCV. Compared with men who had sex with men, people who inject drugs had 82% decreased odds of HBV (AOR = 0.18, 95% CI = 0.05 to 0.63) and 2 times the odds of HCV (AOR = 20.4, 95% CI = 3.32 to 125.3). CONCLUSIONS: During 2001-2019, hepatocellular carcinoma risk declined among people with HIV, though rates remain statistically significantly elevated compared with the general population, particularly among people who inject drugs. Prevention and treatment of HBV/HCV are needed to reduce hepatocellular carcinoma risk among people with HIV.

Severe anal intraepithelial neoplasia trends and subsequent invasive anal cancer in the United States.

BACKGROUND: Anal intraepithelial neoplasia grade III is a precursor to squamous cell carcinoma of the anus for which rates are nearly 20-fold higher in people with HIV than in the general population in the United States. We describe trends in anal intraepithelial neoplasia grade III diagnosis and risk of squamous cell carcinoma of the anus following anal intraepithelial neoplasia grade III by HIV status and sex. METHODS: We used data from a population-based linkage between cancer and HIV registries in 11 US states; Puerto Rico; and Washington, DC, during 1996-2019. We identified all individuals with a diagnosis of anal intraepithelial neoplasia grade III and determined their HIV status. We estimated the average annual percentage change of anal intraepithelial neoplasia grade III using Poisson regression stratified by HIV status and sex. We estimated the 5-year cumulative incidence of squamous cell carcinoma of the anus following an anal intraepithelial neoplasia grade III diagnosis stratified by sex, HIV status, and prior AIDS diagnosis. RESULTS: Among people with HIV, average annual percentage changes for anal intraepithelial neoplasia grade III were 15% (95% confidence interval [CI] = 12% to 17%) per year among females and 12% (95% CI = 11% to 14%) among males. Average annual percentage changes for those without HIV were 8% (95% CI = 7% to 8%) for females and 8% (95% CI = 6% to 9%) for males. Among people with HIV, a prior AIDS diagnosis was associated with a 2.7-fold (95% CI = 2.23 to 3.40) and 1.9-fold (95% CI = 1.72 to 2.02) increased risk of anal intraepithelial neoplasia grade III diagnosis for females and males, respectively. Five-year cumulative incidence of squamous cell carcinoma of the anus following anal intraepithelial neoplasia grade III for people with HIV with a prior AIDS diagnosis were 3.4% and 3.7% for females and males, respectively. CONCLUSIONS: Rates of anal intraepithelial neoplasia grade III diagnoses have increased since 1996, particularly for people with HIV, likely influenced by increased screening. A prior AIDS diagnosis was strongly associated with risk of anal intraepithelial neoplasia grade III diagnosis.

Survival by sex and HIV status in patients with anal cancer in the USA between 2001 and 2019: a retrospective cohort study.

BACKGROUND: The risk of anal cancer is increased among people with HIV, particularly men who have sex with men. Estimating survival by HIV status and sex and identifying groups at high risk is crucial for documenting prognostic differences between populations. We aimed to compare all-cause and anal cancer-specific survival in patients with anal cancer with and without HIV, stratified by sex, and to identify predictors of survival, stratified by HIV status. METHODS: In this retrospective cohort study, we used data from the HIV/AIDS Cancer Match Study of 13 population-based HIV and cancer registries throughout the USA. We included individuals aged 20-79 years diagnosed with invasive anal cancer between 2001 and 2019. To estimate associations between HIV status and both all-cause and anal cancer-specific mortality overall, we used Cox proportional hazards models, adjusting for year of and age at diagnosis, sex, race and ethnicity, histology, cancer stage, region, and treatment. We also calculated sex-specific adjusted hazard ratios (HRs). By HIV status, we identified characteristics associated with mortality. Models among people with HIV were further adjusted for AIDS status and HIV transmission risk group. FINDINGS: Between Jan 1, 2001, and Dec 31, 2019, 1161 (43·6%) of 2662 patients with anal cancer and HIV and 7722 (35·4%) of 21 824 patients without HIV died. HIV was associated with a 1·35 times (95% CI 1·24-1·47) increase in all-cause mortality among male patients and a 2·47 times (2·10-2·90) increase among female patients. Among patients with HIV, all-cause mortality was increased among non-Hispanic Black individuals (adjusted HR 1·19, 95% CI 1·04-1·38), people with AIDS (1·36, 1·10-1·68), people who inject drugs (PWID; 1·49, 1·17-1·90), patients with adenocarcinoma (2·74, 1·82-4·13), and those with no or unknown surgery treatment (1·34, 1·18-1·53). HIV was associated with anal cancer-specific mortality among female patients only (1·52, 1·18-1·97). Among patients with HIV, anal cancer-specific mortality was increased among patients with adenocarcinoma (3·29, 1·89-5·72), those with no or unknown treatment (1·59, 1·17-2·17), and PWID (1·60, 1·05-2·44). INTERPRETATION: HIV was associated with all-cause mortality among patients with anal cancer, especially women. Anal cancer-specific mortality was elevated among female patients with HIV. As screening for anal cancer becomes more widespread, examining the effects of screening on survival by HIV status and sex is crucial. FUNDING: US National Cancer Institute Intramural Research Program.

Real-world use of antiretroviral therapy and risk of cancer among people with HIV in Texas.

BACKGROUND: Combination antiretroviral therapy (cART) may reduce cancer risk among people with HIV (PWH), but cancer-specific associations are incompletely understood. METHODS: We linked HIV and cancer registries in Texas to a national prescription claims database. cART use was quantified as the proportion of days covered (PDC). Cox proportional hazards models assessed associations of cancer risk with cART usage, adjusting for demographic characteristics, AIDS status, and time since HIV report. RESULTS: We evaluated 63 694 PWH followed for 276 804 person-years. The median cART PDC was 21.4% (interquartile range: 0.0-59.8%). cART use was associated with reduced risk of Kaposi sarcoma [adjusted hazard ratio (aHR) 0.48, 95% confidence interval (CI) 0.34-0.68 relative to unexposed status] and non-Hodgkin lymphoma (aHR 0.41, 95% CI 0.31-0.53), liver cancer (aHR 0.61, 95% CI 0.39-0.96), anal cancer (aHR 0.65, 95% CI 0.46-0.92), and a miscellaneous group of 'other' cancers (aHR 0.80, 95% CI 0.66-0.98). In contrast, cART-exposed status was not associated with risk for cervical, lung, colorectal, prostate or breast cancers. CONCLUSION: In a large HIV cohort incorporating data from prescription claims, cART was associated with greatly reduced risks of Kaposi sarcoma and non-Hodgkin lymphoma, and to a lesser degree, reduced risks of liver and anal cancers. These associations likely reflect the beneficial effects of HIV suppression and improved immune control of oncogenic viruses. Efforts to increase cART use and adherence may further decrease cancer incidence among PWH.

Impact of HIV on Anal Squamous Cell Carcinoma Rates in the United States, 2001-2015.

BACKGROUND: Incidence of anal squamous cell carcinoma (SCC) has increased in the United States. People living with HIV (PLWH) have an elevated risk of anal SCC, and changes in the number of anal SCCs among PLWH may have influenced general population trends. METHODS: Data were obtained from a linkage of HIV and cancer registries in 12 US regions. The proportion of anal SCCs occurring among PLWH was estimated by sex, age group, and race and ethnicity. To assess the impact of anal SCCs among PLWH on general population trends, annual percent changes (APCs) in incidence rates including and excluding anal SCCs among PLWH were estimated. RESULTS: Between 2001 and 2015, 14.5% of 16 110 anal SCC diagnoses occurred in PLWH. In 2013-2015, 35% of anal SCCs among men occurred in PLWH, but only 2% among women. The proportion of anal SCCs among PLWH was highest among 20- to 49-year-olds and Black and Hispanic individuals. General population anal SCC trends among men were strongly influenced by anal SCCs among PLWH: rates increased 4.6%/y (95% confidence interval [CI] = 1.4% to 8.0%) from 2001 to 2009 followed by a statistically non-significant decline (APC = -2.7%/y, 95% CI = -7.1% to 2.0%) from 2009 to 2015, but without anal SCCs among PLWH, rates were stable (APC = 0.7%/y, 95% CI = -0.8% to 2.3%). Anal SCC rates among women increased 3.8%/y (95% CI = 3.2% to 4.4%) during 2001-2012 and then declined statistically non-significantly (APC = -3.8%/y, 95% CI = -6.9% to -0.6%), and anal SCCs among PLWH had little impact on these trends. CONCLUSIONS: During 2001-2015, anal SCCs among PLWH contributed strongly to changes in incidence trends in the general US population among men, but not women.

Epidemiology of Cervical Adenocarcinoma and Squamous Cell Carcinoma Among Women Living With Human Immunodeficiency Virus Compared With the General Population in the United States.

BACKGROUND: Although cervical cancer risk overall is elevated among women living with human immunodeficiency virus (HIV; WLH), it is unclear whether risks are similarly elevated across histologic subtypes. METHODS: Data from the HIV/AIDS Cancer Match Study, a linkage of 12 US HIV and cancer registries during 1996 -2016, were used. Cervical cancers were categorized as adenocarcinoma (AC), squamous cell carcinoma (SCC), or other histologic subtype. Standardized incidence ratios compared rates of AC and SCC in WLH to those in general population. For WLH, risk factors for AC and SCC were evaluated using Poisson regression. Five-year survival was estimated by HIV status and histology. RESULTS: Overall, 62 615 cervical cancers were identified, including 609 in WLH. Compared with the general population, incidence of AC was 1.47 times higher (95% confidence interval [CI]: 1.03-2.05) and SCC was 3.62 times higher among WLH (95% CI: 3.31-3.94). Among WLH, there was no difference in AC rates by race/ethnicity or HIV transmission group, although SCC rates were lower among White women (vs Black) and higher among women who inject drugs (vs heterosexual transmission). Among WLH, 5-year overall survival was similar for AC (46.2%) and SCC (43.8%) but notably lower than for women not living with HIV. CONCLUSIONS: Among WLH, AC rates were modestly elevated, whereas SCC rates were greatly elevated compared with the general population. These findings suggest there may be differences in the impact of immunosuppression and HIV in the development of AC versus SCC, given their common etiology in human papillomavirus infection.

Kaposi Sarcoma Incidence, Burden, and Prevalence in United States People with HIV, 2000-2015.

BACKGROUND: The introduction of combination antiretroviral therapy (cART) has led to a significant reduction in Kaposi sarcoma (KS) incidence among people with HIV (PWH). However, it is unclear if incidence has declined similarly across key demographic and HIV transmission groups and the annual number of incident and prevalent KS cases remains unquantified. METHODS: Using population-based registry linkage data, we evaluated temporal trends in KS incidence using adjusted Poisson regression. Incidence and prevalence estimates were applied to CDC HIV surveillance data, to obtain the number of incident (2008-2015) and prevalent (2015) cases in the United States. RESULTS: Among PWH, KS rates were elevated 521-fold [95% confidence intervals (CI), 498-536] compared with the general population and declined from 109 per 100,000 person-years in 2000 to 47 per 100,000 person-years in 2015, at an annual percentage change of -6%. Rates declined substantially (P trend < 0.005) across all demographic and HIV transmission groups. Of the 5,306 new cases estimated between 2008 and 2015, 89% occurred among men who have sex with men. At the end of 2015, 1,904 PWH (0.20%) had been diagnosed with KS in the previous 5 years. CONCLUSIONS: A consistent gradual decline in KS incidence has occurred among PWH in the United States during the current cART era. This decrease is uniform across key demographic and HIV transmission groups, though rates remain elevated relative to the general population. IMPACT: Continued efforts to control HIV through early cART initiation and retention in care need to be maintained and possibly expanded to sustain declines.

Cervical cancer incidence stratified by age in women with HIV compared with the general population in the United States, 2002-2016.

OBJECTIVE: Recommendations for the age of initiating screening for cervical cancer in women with HIV (WWH) in the United States have not changed since 1995 when all women (regardless of immune status) were screened for cervical cancer from the age of onset of sexual activity, which often occurs in adolescence. By 2009, recognizing the lack of benefit as well as harms in screening young women, guidelines were revised to initiate cervical cancer screening for the general population at age 21 years. By comparing cervical cancer incidence in young WWH to that of the general population, we assessed the potential for increasing the recommended age of initiating cervical cancer screening in WWH. DESIGN: We compared age-specific invasive cervical cancer (ICC) rates among WWH to the general population in the United States HIV/AIDS Cancer Match Study. METHODS: We estimated standardized incidence ratios as the observed number of cervical cancer cases among WWH divided by the expected number, standardized to the general population by age, race/ethnicity, registry, and calendar year. RESULTS: ICC rates among WWH were elevated across all age groups between ages 25 and 54 years (SIR = 3.80; 95% CI 3.48--4.15) but there were zero cases among ages less than 25 years. CONCLUSION: The absence of ICC among WWH less than 25 years supports initiating cervical cancer screening at age 21 years, rather than adolescence, to prevent cancers in WWH at ages with higher risk of ICC.