Abstract
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.
Anal cancer is a rare malignancy that comprises 0.5% of all new cancer cases in the United States. Between the 1970s and 2017, anal cancer incidence increased from 0.79 to 1.50 per 100 000 person-years in men and from 1.04 to 2.10 per 100 000 person-years in women (1). More than 80% of anal cancers in the United States are squamous cell carcinomas (SCCs), 90% of which are caused by high-risk human papillomavirus (HPV) infection (2). Behavioral risk factors related to HPV acquisition, including number of sexual partners and engaging in receptive anal intercourse, are also associated with anal SCC risk.
People living with HIV (PLWH) have anal cancer rates that are nearly 20 times higher than the general population; men who have sex with men (MSM) with HIV have rates that are elevated nearly 40-fold (3). Immunosuppression due to HIV is associated with elevated risk of HPV-related lesions and reduced HPV clearance, leading to anal cancer precursor lesions (4,5). Among PLWH, sustained undetectable plasma HIV viral load is associated with a lower prevalence of abnormal anal cytology and anal cancer risk, indicating successful combination antiretroviral therapy (cART) can be protective against anal cancer (6).
During 1980-2005, 28.4% of all anal cancers in men and 1.2% of anal cancers in women occurred among PLWH (7). An estimated 50% of the increase in anal cancer incidence in men in the general population was due to anal cancers occurring among PLWH. Given rising anal SCC rates and the contribution of PLWH to these trends, we sought to examine more recent data to understand the impact of anal SCC cases among PLWH on general population rates of anal SCC between 2001 and 2015 in 12 US regions.
Methods
Study Population
This study used data from 2001-2015 from the HIV/AIDS Cancer Match (HACM) Study (http://hivmatch.cancer.gov), a registry-based cohort study linking 12 population-based HIV and cancer registries. The registries providing data (with years of coverage) were Colorado (2001-2015), Connecticut (2002-2015), District of Columbia (2007-2015), Georgia (2004-2012), Louisiana (2001-2015), Maryland (2008-2015), Michigan (2001-2015), New Jersey (2001-2012), New York (2001-2012), North Carolina (2001-2014), Puerto Rico (2003-2015), and Texas (2001-2015). The HACM Study has secured institutional review board approval at participating registries when required. Analysis was restricted to individuals aged 20-79 years.
In this study, invasive anal SCC was defined by the International Classification of Disease for Oncology, 3rd edition, corresponding to topography codes C210 (anus, not otherwise specified) and C211 (anal canal) (8) and histology codes (ICD-O-3 codes 8050–8084).
Statistical Analysis
Anal SCC cases were categorized by calendar year, age (in 10-year age categories), sex, race and ethnicity (Hispanic, non-Hispanic Black [ie, Black], non-Hispanic White [ie, White], and other or unknown race [includes individuals who are Asian, Pacific Islander and American Indian or Alaska Native]), and registry. Race, ethnicity, and sex were recorded by HIV surveillance systems. Men with HIV were further classified according to their HIV transmission risk group as MSM and other men.
To correct the imperfect ascertainment of HIV status among anal SCC cases during linkage of HIV and cancer registries, we estimated the sensitivity of the linkage and divided the observed number of anal SCC cases among PLWH by this estimate, as described previously and in the Supplementary Methods (available online) (7,9).
We estimated the proportion of anal SCC cases in the general US population occurring among PLWH, stratified by sex, 2 age groups (20-49 years and 50-79 years), race and ethnicity, and calendar period (2001-2004, 2005-2008, 2009-2012, and 2013-2015). We also estimated the annual incidence rates of anal SCCs per 100 000 person-years in the general population including and excluding anal SCC cases among PLWH.
Only 4 registries (Colorado, Louisiana, Michigan, Texas) had data available for the entire study period. Thus, we conducted multiple imputations based on parametric models for years without available data to obtain person-years and anal SCC counts among the general and PLWH populations (described in Supplementary Methods, available online). Final estimates were computed as the mean of 5 multiple imputation iterations. To compute variances, we used a parametric bootstrap procedure with 500 iterations as described in the Supplementary Methods (available online), similar to a previously published approach (7). For each bootstrap iteration, we resampled the original data with replacement and then imputed the data for that particular bootstrap realization as described in the Supplementary Material (available online). Thus, the bootstrap variance accommodates all sources of variation, including the component of variance coming from the multiple imputations.
Incidence rates were directly age-standardized using the 2000 US standard population as a reference. Joinpoint regression analysis with bootstrap standard errors was used to estimate annual percent changes (APCs) in age-standardized anal SCC incidence rates and to identify statistically significant changes in the regression slopes over time in the general population and after excluding anal SCC cases occurring among PLWH (10,11). All analyses were conducted in SAS 9.4 (12). All statistical tests were 2-sided, with P less than .05 as the cut-off for statistical significance.
Results
Between 2001 and 2015, in 12 US regions representing 100 million individuals or nearly one-third (30.4%) of the US population, there were an estimated 16 110 anal SCC cases, with an estimated 6277 occurring in men and 9833 occurring in women. Forty-four percent of PLWH in the United States live in these 12 regions (13).
For men, 32.5% of anal SCCs occurred in PLWH, and for women, 3.0% occurred in PLWH (see Table 1). The percentage of anal SCCs among men with HIV increased from 29.1% (95% CI = 26.3% to 32.2%) in 2001-2004 to 34.9% (95% CI = 31.2% to 40.0%) in 2013-2015. Among women, the percentage remained stable from 2.6% (95% CI = 1.8% to 3.4%) in 2001-2004 to 2.3% (95% CI = 1.7% to 3.2%) in 2013-2015.
Table 1.
General population and the estimated proportion of anal SCC cases occurring among PLWH, 2001-2015a
| Category | Men |
Women |
|||
|---|---|---|---|---|---|
| No. of cancers | With HIV infection | No. of cancers | With HIV infection | ||
| No. (95% CI) | % of total (95% CI) | No. (95% CI) | % of total (95% CI) | ||
| Total | 6277 (6032 to 6577) | 32.5 (31.3 to 34.4) | 9833 (9483 to 10314) | 3.0 (2.6 to 3.5) | |
| Age at cancer diagnosis | |||||
| 20-49 y | 2154 (2033 to 2272) | 56.0 (53.5 to 58.4) | 2083 (1930 to 2228) | 8.5 (7.2 to 10.0) | |
| 50-79 y | 4123 (3944 to 4362) | 20.2 (18.0 to 22.4) | 7750 (7478 to 8166) | 1.6 (1.3 to 1.9) | |
| Race and ethnicity | |||||
| Black | 1318 (1252 to 1420) | 57.3 (54.7 to 60.3) | 1304 (1210 to 1411) | 12.4 (10.3 to 14.7) | |
| 20-49 y | 659 (610 to 710) | 72.9 (69.1 to 76.2) | 372 (324 to 420) | 27.7 (22.9 to 33.0) | |
| 50-79 y | 658 (607 to 735) | 41.6 (37.9 to 46.8) | 932 (863 to 1024) | 6.3 (4.8 to 8.4) | |
| Hispanic | 608 (552 to 663) | 52.0 (47.0 to 55.8) | 925 (851 to 992) | 8.6 (6.5 to 10.7) | |
| 20-49 y | 282 (245 to 309) | 72.3 (66.8 to 77.9) | 192 (157 to 211) | 24.1 (17.4 to 31.2) | |
| 50-79 y | 326 (288 to 372) | 34.4 (28.3 to 39.7) | 733 (671 to 795) | 4.5 (3.0 to 6.3) | |
| White | 4299 (4103 to 4551) | 22.1 (20.9 to 24.2) | 7494 (7215 to 7898) | 0.8 (0.5 to 1.0) | |
| 20-49 y | 1193 (1103 to 1287) | 42.9 (40.1 to 46.5) | 1497 (1374 to 1635) | 1.7 (1.0 to 2.4) | |
| 50-79 y | 3106 (2944 to 3322) | 14.1 (12.8 to 16.2) | 5997 (5769 to 6374) | 0.5 (0.3 to 0.7) | |
| Other | 53 (39 to 70) | 35.7 (20.8 to 51.2) | 109 (85 to 129) | 2.4 (0.0 to 6.4) | |
| 20-49 | 20 (11 to 30) | 48.6 (21.2 to 73.3) | 22 (12 to 32) | 10.2 (0.0 to 27.8) | |
| 50-79 | 33 (22 to 45) | 27.9 (11.4 to 47.4) | 88 (69 to 105) | 0.5 (0.0 to 1.9) | |
| Calendar period | |||||
| 2001-2004 | 1261 (1146 to 1355) | 29.1 (26.3 to 32.2) | 1872 (1739 to 2004) | 2.6 (1.8 to 3.4) | |
| 2005-2008 | 1614 (1529 to 1697) | 32.9 (30.9 to 35.4) | 2372 (2257 to 2467) | 3.3 (2.6 to 4.1) | |
| 2009-2012 | 1898 (1812 to 1989) | 32.6 (30.6 to 34.7) | 3004 (2901 to 3105) | 3.7 (3.0 to 4.4) | |
| 2013-2015 | 1505 (1353 to 1761) | 34.9 (31.2 to 40.0) | 2583 (2360 to 2996) | 2.3 (1.7 to 3.2) | |
CI = confidence interval; PLWH = people living with HIV; SCC = squamous cell carcinoma.
During 2001-2015, an estimated 56.0% (95% CI = 53.5% to 58.4%) of anal SCCs among 20- to 49-year-old men occurred among PLWH compared with only 20.2% (95% CI = 18.0% to 22.4%) among 50- to 79-year-old men. Among women, 8.5% (95% CI = 7.2% to 10.0%) of anal SCCs among 20- to 49-year-olds and 1.6% (95% CI = 1.3% to 1.9%) of anal SCCs among 50- to 79-year-olds occurred among PLWH.
Black and Hispanic men and women, and men and women in the other or unknown racial group, had higher proportions of anal SCC cases occurring among PLWH compared with White men and women. Among Black men, 57.3% (95% CI = 54.7% to 60.3%) of anal SCCs occurred in PLWH, which was more than double the proportion in White men (22.1%, 95% CI = 20.9% to 24.2%). Among Black women, 12.4% (95% CI = 10.3% to 14.7%) of anal SCCs occurred in PLWH, which was roughly 15 times higher than in White women (0.8%, 95% CI = 0.5% to 1.0%). In Hispanic men, 52.0% (95% CI = 47.0% to 55.8%) of anal SCCs occurred in PLWH, and 8.6% (95% CI = 6.5% to 10.7%) occurred in PLWH among Hispanic women.
Male anal SCC incidence trends increased during 2001-2009 (APC = 4.6%/y, 95% CI = 1.4% to 8.0%) followed by a statistically non-significant decrease (2009-2015; APC = −2.7%/y, 95% CI = −7.1% to 2.0%) (see Table 2). These trends were clearly influenced by anal SCCs among PLWH (see Figure 1). After exclusion of anal SCCs among PLWH, no statistically significant change in anal SCC incidence was observed over the time period (APC = 0.7%/y, 95% CI = −0.8% to 2.3%). Anal SCCs among PLWH had a larger impact on anal SCC trends among 20- to 49-year-old men. In this age group, anal SCC incidence increased 5.3%/y (95% CI = 1.0% to 9.6%) from 2001 to 2009 and decreased by 8.1%/y (95% CI = −14.1% to −1.6%) from 2009 to 2015 in the general population. After excluding anal SCCs among PLWH, incidence declined statistically non-significantly by 1.3%/y (95% CI = −3.9% to 1.4%) for 2001-2015. Incidence trends were similar among 50- to 79-year-old men both including and excluding anal SCCs from PLWH.
Table 2.
Trends in anal SCC incidence between 2001 and 2015
| Category | All anal SCCs |
Anal SCCs excluding cases among PLWH |
||||
|---|---|---|---|---|---|---|
| Segment no.a | APC in incidenceb | Segment, y | Segment no.a | APC in incidenceb | Segment, y | |
| (95% CI) | (95% CI) | |||||
| Men | ||||||
| Total | 1 | 4.6 (1.4 to 8.0) | 2001-2009 | 1 | 0.7 (−0.8 to 2.3) | 2001-2015 |
| 2 | −2.7 (−7.1 to 2.0) | 2009-2015 | — | — | — | |
| Age group, y | ||||||
| 20-49 | 1 | 5.3 (1.0 to 9.6) | 2001-2009 | 1 | −1.3 (−3.9 to 1.4) | 2001-2015 |
| 2 | −8.1 (−14.1 to −1.6) | 2009-2015 | — | — | — | |
| 50-79 | 1 | 2.6 (1.2 to 4.0) | 2001-2015 | 1 | 1.3 (0.0 to 2.7) | 2001-2015 |
| Race and ethnicity | ||||||
| Black | 1 | 7.8 (2.2 to 13.7) | 2001-2009 | 1 | 8.7 (0.3 to 17.8) | 2001-2008 |
| 2 | −6.7 (−13.2 to 0.3) | 2009-2015 | 2 | −8.3 (−15.0 to −1.2) | 2008-2015 | |
| Hispanic | 1 | 1.2 (−2.6 to 5.1) | 2001-2015 | 1 | −0.8 (−4.1 to 2.7) | 2001-2015 |
| White | 1 | 1.6 (0.3 to 2.8) | 2001-2015 | 1 | 1.2 (−0.3 to 2.7) | 2001-2015 |
| Other or unknown race | 1 | 0.0 (−5.8 to 6.1) | 2001-2015 | 1 | −3.8 (−10.5 to 3.4) | 2001-2015 |
| Women | ||||||
| Total | 1 | 3.8 (3.2 to 4.4) | 2001-2012 | 1 | 3.7 (3.1 to 4.2) | 2001-2012 |
| 2 | −3.8 (−6.9 to −0.6) | 2012-2015 | 2 | −2.4 (−6.4 to −1.8) | 2012-2015 | |
| Age group, y | ||||||
| 20-49 | 1 | 0.7 (−0.4 to 1.9) | 2001-2015 | 1 | 0.4 (−0.5 to 1.4) | 2001-2015 |
| 50-79 | 1 | 4.6 (4.1 to 5.1) | 2001-2012 | 1 | 4.5 (4.0 to 5.0) | 2001-2012 |
| 2 | −2.5 (−5.9 to 0.9) | 2012-2015 | 2 | −2.2 (−5.5 to 1.2) | 2012-2015 | |
| Race and ethnicity | ||||||
| Black | 1 | 2.1 (0.6 to 3.6) | 2001-2015 | 1 | 1.7 (0.5 to 3.0) | 2001-2015 |
| Hispanic | 1 | 0.7 (−0.9 to 2.4) | 2001-2015 | 1 | −1.9 (−5.3 to 1.7) | 2001-2008 |
| — | — | — | 2 | 12.0 (−10.4 to 40.0) | 2008-2011 | |
| — | — | — | 3 | −7.6 (−13.9 to −0.9) | 2011-2015 | |
| White | 1 | 4.8 (3.7 to 6.0) | 2001-2011 | 1 | 4.5 (3.6 to 5.4) | 2001-2012 |
| 2 | −1.6 (−5.6 to 2.6) | 2011-2015 | 2 | −3.4 (−9.5 to 3.1) | 2012-2015 | |
| Other or unknown race | 1 | −1.5 (−6.1 to 3.2) | 2001-2015 | 1 | −1.7 (−6.6 to 3.5) | 2001-2015 |
Segment numbers represent temporally consecutive trends that are estimated by Joinpoint software as the minimal number of statistically significantly different slope values in a Joinpoint model of age-adjusted incidence rates. APC = annual percent change; CI = confidence interval; PLWH = people living with HIV; SCC = squamous cell carcinoma.
APCs in anal SCC incidence were estimated using Joinpoint software.
Figure 1.
Age-adjusted anal squamous cell carcinoma (SCC) incidence (to 2000 standardized population) in the general population including and excluding anal SCCs among PLWH, by age and sex, between 2001 and 2015. The solid lines represent the overall incidence rates of anal SCCs in the general population; the dashed lines represent the incidence rates for anal SCC without anal SCCs among PLWH. A) Incidence rates in men. B) Incidence rates in women. C) Incidence rates in 20- to 49-year-old men. D) Incidence rates in 20- to 49-year-old women. E) Incidence rates in 50- to 79-year-old men. F) Incidence rates in 50- to 79-year-old women.
In Black men, incidence increased by 7.8%/y (95% CI = 2.2% to 13.7%) from 2001 to 2009 and decreased by 6.7%/y (95% CI = −13.2% to 0.3%) during 2009-2015. After excluding PLWH, trends were similar to that of the full population (Table 2; Supplementary Figure 1, available online). For Hispanic men, incidence was stable from 2001 to 2015 with and without anal SCCs among PLWH. In White men, incidence increased 1.6%/y (95% CI = 0.3% to 2.8%) from 2001 to 2015, and there was no statistically significant trend following exclusion of anal SCCs among PLWH (Supplementary Figure 1, available online).
Female anal SCC incidence rates increased by 3.8%/y (95% CI = 3.2% to 4.4%) from 2001 to 2012 and decreased by 3.8%/y (95% CI = −6.9% to −0.6%) from 2012 to 2015 and were essentially unchanged following exclusion of anal SCCs among PLWH (Table 2). Trends in incidence rates also did not change after exclusion of PLWH for either 20- to 49-year-old or 50- to 79-year-old women. Incidence in 50- to 79-year-old women increased by 4.6%/y (95% CI = 4.1% to 5.1%) until 2012 before decreasing, though not statistically significantly.
Trends in anal SCC incidence rates among women with anal SCC were not affected by anal SCCs in PLWH among Black or White women. In the general population, anal SCC incidence among Black women increased 2.1%/y (95% CI = 0.6% to 3.6%) across 2001-2015. Among White women, incidence increased between 2001 and 2011 by 4.8%/y (95% CI = 3.7% to 6.0%) and decreased statistically non-significantly by 1.6%/y (95% CI = −5.6% to 2.6%) from 2011 to 2015. In Hispanic women, incidence rates of anal SCC remained stable between 2001 and 2015 (APC = 0.7%, 95% CI = −0.9% to 2.4%). After exclusion of anal SCCs among PLWH, there was no statistically significant change in incidence rates during 2001-2011, but between 2011 and 2015, the incidence decreased by 7.6%/y (95% CI = −13.9% to −0.9%).
Discussion
Between 2001 and 2015, nearly one-third of anal SCC cases among men in the general population of 12 US regions occurred among PLWH. As the fraction of anal SCCs occurring among men with HIV increased over time, PLWH had a notable impact on anal SCC trends in the general population, accounting for the observed increase between 2001 and 2009, followed by a statistically non-significant decline from 2010 to 2015. The proportion of anal SCCs occurring among PLWH was notably higher among 20- to 49-year-old Black and Hispanic men. Three percent of anal SCCs in women occurred in PLWH, with no impact on the general population incidence trends over time.
Our study extended a previous analysis of HACM data from 1980 to 2005 (7). Similar to this older analysis, anal SCCs among PLWH contributed strongly to anal cancers among men (28.4% in 1980-2005 vs 32.5% in 2001-2015) and far less so among women (1.2% vs 3.0%). In both studies, the prevalence of HIV was greatest in anal SCCs occurring among 20- to 49-year-olds and lowest in White men and women. Whereas the previous study reported increases in anal cancer incidence rates during 1980-2005, this study has reported a plateau in anal SCC rates beginning in 2009 among men and a decline beginning in 2012 among women.
Immunosuppression plays a role in anal SCC development. Anal cancer incidence is higher in solid organ transplant patients due to clinical immunosuppression to prevent organ rejection (14). In PLWH, low CD4+ cell count was found to be a risk factor for the development of anal cancer (15). PLWH also have a greater likelihood of recurrent anal high grade squamous intraepithelial lesions (HSIL) and relapse rate of anal cancer following treatment, indicating the presence of long-term immune dysregulation may mediate cancer risk, regardless of cART history (6). Widespread treatment with cART in the United States has vastly reduced HIV mortality, and aging PLWH are increasingly susceptible to non-AIDS defining cancers. Anal cancer is one of the most common non-AIDS defining cancers occurring among PLWH in the United States, estimated to be the fourth most common cancer type in 2020 (16).
The proportion of anal SCCs among PLWH was substantially higher among men compared with women. This is primarily due to a higher prevalence of HIV among US men and a higher prevalence of anal HPV infection among MSM, who are disproportionately at risk for anal cancer than other HIV risk groups (17). The proportion of anal SCCs occurring among PLWH was also higher in 20- to 49-year-old men than in 50- to 79-year-old men. This is due to the lower incidence rate of anal cancer among younger age groups in the general population such that the proportional representation of PLWH anal SCC cases is relatively larger. In addition, in the United States, Black and Hispanic men and women bear a disproportionate burden of the HIV epidemic (13). These disparities are likely attributable to socio-ecological factors that persistently affect HIV prevention and treatment outcomes, including lack of access to culturally appropriate HIV testing and treatment, HIV-related stigma, knowledge gaps, comorbid mental health conditions, and substance use (18).
We have also shown that anal SCC cases among men with HIV have strongly influenced general population anal SCC trends in the United States; general population rates increased between 2001 and 2009 before statistically non-significantly declining between 2009 and 2015, whereas a stable rate was observed after excluding anal SCCs among PLWH. The recent stabilization after years of increasing SCC rates may be driven by a more stable contribution of anal SCCs among men with HIV in recent periods. This could be because the number of anal cancers diagnosed each year among PLWH has begun to decline due to declining incidence rates among PLWH and decreasing population size among PLWH (16). We did not observe differences in incidence trends following exclusion of cases living with HIV for Black or Hispanic men. However, we note that APCs capture only the slope of the incidence trends over time. Given that the proportion of anal SCCs occurring among PLWH is very high in these 2 groups, this lack of difference indicates that the substantial contribution of anal SCCs among PLWH to incidence rates in these 2 groups has remained relatively stable for the entirety of the study period.
In contrast, increasing anal SCC incidence rates among women in the United States have not been driven by women with HIV. It has been proposed that the increasing rates of anal cancer among women in the general population are driven by an increase in anal HPV infection due to a change in sexual behaviors across birth cohorts, including increases in lifetime sexual partners, lower age at sexual debut, and increased prevalence of receptive anal intercourse (19). Individual anal HPV exposure is also correlated with cervical HPV exposure, which has increased in prevalence over time. Though women in their 20s and 30s may have been eligible for HPV vaccination, early uptake of the vaccine in the United States was low, and the impact of HPV vaccination on anal cancer rates will not be notable until those vaccinated reach older ages when anal cancer incidence is higher. Rising rates of autoimmune disease have also been proposed as a potential explanation for increasing anal cancer rates, because 80% of patients diagnosed with autoimmune disorders are female (14,20).
HPV vaccination among both men and women would substantially reduce anal cancer incidence, along with the risk of other HPV-associated cancers, and more research is needed to understand the effectiveness of HPV vaccination among PLWH. Another preventive option is anal cancer screening of high-risk groups by anal Pap test to detect abnormal cytology. Current screening methods, including high-resolution anoscopy, exhibit variable sensitivity (69%-93%) and specificity (32%-59%) in finding high-grade intraepithelial neoplasia, even in high-prevalence populations like PLWH (21,22). Currently, the New York State Department of Health AIDS Institute recommends digital anal-rectal exams for all people living with HIV 35 years old and older, and annual anal pap testing for PLWH who are MSM, transgender women, cisgender women, and transgender men (23). Researchers evaluated the efficacy of treatment vs monitoring of biopsy-confirmed HSIL in a randomized control trial (the ANCHOR Study) in 4446 PLWH older than 35 years. The study was recently halted after interim results showed a clear benefit of treatment of HSIL lesions (24). Given the benefits of early detection and treatment of anal cancer and its precursors, this study shows that focusing these efforts on men living with HIV could substantially reduce general population rates of anal cancer among men.
This study’s strength is the use of a large, population-based data linkage study from 12 diverse regions of the United States over a long period of follow-up. We carefully accommodated missing values to generate a more complete picture of anal cancer trends across the study period. The primary limitation of this study is the inclusion of data from US areas with an overrepresentation of PLWH, limiting the generalizability of study conclusions to the whole US population. Despite this, because the national US HIV prevalence falls within the HIV prevalence range observed in the regions included in this study, it may be reasonable to assume that our results may encompass the picture of anal SCCs and HIV infection in the broader United States. This study also posits lower incidence rates of anal cancer for 2013-2015 for both sexes compared with previous studies (25).
This may be due to geographical heterogeneity in race and ethnicity make-up and potentially anal cancer screening practices. The study does not capture undiagnosed PLWH, which could exclude up to 13% of PLWH, and does not include individual-level information on anal Pap testing, HPV vaccination, HPV infection, cigarette smoking, or other immune-related conditions.
In conclusion, 1 out of 3 anal SCCs in men and 1 out of 30 anal SCCs in women in the United States during 2001-2015 occurred among PLWH. Among men, increased rates of anal SCC between 2001 and 2009 followed by a statistically non-significant downward trend were strongly influenced by cases among PLWH. This was particularly true for younger males. Incidence of anal SCC in females increased over the study period, driven by increases in older females, but few cases occurred among PLWH. Public health measures aimed at preventing anal SCCs among PLWH could substantially reduce anal SCCs in the US population.
Funding
This research was supported in part by the Intramural Research Program of the National Cancer Institute.
The following cancer registries were supported by the cooperative agreement funded by the Centers for Disease Control and Prevention, National Program of Cancer Registries: Colorado (NU58DP006347-01), Georgia (5U58DP003875-01), Louisiana (NU58DP006332-03-00), Maryland (NU58DP006333), Massachusetts (NU58DP006271-04-00), Michigan (17NU58DP006334), New Jersey (NU58/DP003931-05-00), New York (6NU58/DP006309), North Carolina (1NU58DP006281), and Texas (1NU58DP006308). District of Columbia is supported by the Centers for Disease Control and Prevention cooperative agreement DP006302.
The following cancer registries were supported by the SEER Program of the National Cancer Institute: Connecticut (HHSN261201300019I), Louisiana (HHSN261201800007I/HHSN26100002), Massachusetts (HHSN261201800008l), New Jersey (HHSN261201300021I, N01-PC-2013-00021), and New York (HHSN261201800009I). The New Jersey State Cancer Registry was also supported by the state of New Jersey, the Maryland Cancer Registry was supported by the State of Maryland and the Maryland Cigarette Restitution Fund, the Louisiana Tumor Registry was also supported by the state of Louisiana (0587200015), and the New York State Cancer Registry was also supported by the state of New York.
The following HIV registries were supported by HIV Incidence and Case Surveillance Branch of the Centers for Disease Control and Prevention, National HIV Surveillance Systems: Colorado (NU62PS003960), Connecticut (5U62PS001005-05), Louisiana (NU62PS924522-02-00), Michigan (U62PS004011-02), New Jersey (U62PS004001-2), New York (NU62PS924546-02-00; PS18-1802: Integrated HIV Surveillance and Prevention Programs for Health Departments, National Center for HIV, Viral Hepatitis, STD, and TB Prevention [NCHHSTP]).
Notes
Role of the funder: The funder approved a final version of this manuscript, but did not contribute to the design, analysis and writing of the manuscript.
Disclosures: The authors have no conflicts of interest to report.
Author contributions: Conceptualization: MS and EZ. Data curation: AA, JH, AM and KP. Formal analysis: EZ and RP. Supervision: MS and RP. Writing—original draft: EZ and MS. Writing—review and editing: RP, AA, MC, JH, MH, AM, KP, EE and MS.
Acknowledgements: The authors gratefully acknowledge the support and assistance provided by individuals at the following state HIV/AIDS and cancer registries: Colorado, Connecticut, District of Columbia, Georgia, Louisiana, Maryland, Massachusetts, Michigan, New Jersey, New York, North Carolina, Puerto Rico, and Texas. We also thank Timothy McNeel at Information Management Services for programming support.
Disclaimers: The views expressed in this article are those of the authors and should not be interpreted to reflect the views or official policies of the National Cancer Institute, Centers for Disease Control and Prevention or the Department of Health and Human Services, HIV/AIDS or cancer registries, or their contractors, nor does the mention of trade names, commercial practices, or organizations imply endorsement by the U.S. Government.
Supplementary Material
Contributor Information
Elizabeth R Zhang, Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Ruth M Pfeiffer, Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
April Austin, New York Department of Health, New York State Cancer Registry, Albany, NY, USA.
Megan A Clarke, Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Jennifer Hayes, Maryland Department of Health, Maryland Cancer Registry, Baltimore, MD, USA.
Marie-Josèphe Horner, Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Analise Monterosso, Department of State Health Services, HIV/STD/HCV Epidemiology and Surveillance Branch, Austin, TX, USA.
Karen S Pawlish, New Jersey Department of Health, New Jersey State Cancer Registry, Trenton, NJ, USA.
Eric A Engels, Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Meredith S Shiels, Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Data Availability
The data underlying this article cannot be shared publicly due to the terms of the NCI’s data use agreements with cancer and HIV surveillance systems.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data underlying this article cannot be shared publicly due to the terms of the NCI’s data use agreements with cancer and HIV surveillance systems.