Systematic Review of Racial Disparities in Human Papillomavirus–Associated Anal Dysplasia and Anal Cancer Among Men Who Have Sex With Men

Abstract

We systematically reviewed the literature on anal human papillomavirus (HPV) infection, dysplasia, and cancer among Black and White men who have sex with men (MSM) to determine if a racial disparity exists. We searched 4 databases for articles up to March 2014.

Studies involving Black MSM are nearly absent from the literature. Of 25 eligible studies, 2 stratified by race and sexual behavior. Both reported an elevated rate of abnormal anal outcomes among Black MSM. White MSM had a 1.3 times lower prevalence of group-2 HPV (P < .01) and nearly 13% lower prevalence of anal dysplasia than did Black MSM.

We were unable to determine factors driving the absence of Black MSM in this research and whether disparities in clinical care exist. Elevated rates of abnormal anal cytology among Black MSM in 2 studies indicate a need for future research in this population.

Although it is relatively rare in the general US population, anal cancer and its precursors disproportionately affect men who have sex with men (MSM) and people living with HIV. Anal cancer rates have been found to be highest among HIV-infected MSM with an estimated anal cancer incidence of 131 per 100 000 for HIV-infected MSM, 46 per 100 000 for HIV-infected heterosexual men, and 30 per 100 000 in HIV-infected women.¹ Furthermore, although the introduction of antiretroviral therapy has led to an increased life expectancy for HIV-infected individuals, a concomitant increase in anal cancer cases has occurred since 1996.²

Anal intraepithelial neoplasia is the immediate precursor of anal cancer and presents as a low-grade squamous intraepithelial lesion or as a high-grade squamous intraepithelial lesion. Infection with human papillomavirus (HPV) is thought to cause the majority of anal intraepithelial neoplasia. Group-1 high-risk HPV types (HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) are strongly carcinogenic; group-2 high-risk HPV types (HPV 26, 30, 34, 53, 66, 67, 68, 69, 70, 73, 82, 85, and 97) are weaker carcinogens and “probable” or “possible” causes of cancer.³ Although up to 90% of HPV infections are cleared within 2 years in the general population, HPV is much more likely to lead to anal cancer in HIV-infected individuals.⁴ Furthermore, rates of anal intraepithelial neoplasia have increased markedly among HIV-infected MSM.²

Though MSM have been established as a group at high risk for anal cancer, no studies have been designed to study racial differences among MSM in anal HPV, dysplasia, and cancer. A focus on Black MSM is important in light of several factors that may have a differential impact on anal cancer risk in this population. First, oncogenic HPV subtypes have been found to be variably distributed across populations based upon race. For example, in 2 recent studies, Black women were found to have higher rates of HPV (such as 33, 35, 58, and 68) that are not included in the existing HPV vaccines.^5,6 Second, transmission of HPV within sexual networks⁷ may propagate certain subtypes with variable oncogenic potential. Black communities, including Black MSM, are known to have more within-group sexual partners than Whites and other ethnic minorities who are more likely to have sexual mixing patterns involving individuals of other racial groups.^7,8 Third, Black MSM have the highest HIV incidence rate compared with other MSM populations⁹ and thus will increasingly be at risk for anal cancer. Finally, marked disparities across access to care, prevention services, and health insurance¹⁰ put Black MSM at increased risk for preventable oncogenic anal HPV, dysplasia, and cancer.

Previous reviews of anal HPV infection, dysplasia, and cancer have identified MSM as a high-risk group, highlighted an absence of young MSM from anal HPV studies, offered an explanation for the increase in anal cancer incidence, and explored cost-effectiveness of routine anal screening.^11–14 We built upon previous work by comparing anal HPV infection, dysplasia, and cancer among MSM with data from past studies. We had 2 objectives with the systematic review. First, we aimed to determine if a racial disparity exists in anal HPV infection, dysplasia, and cancer screening. Second, we aimed to determine if a racial disparity exists in anal HPV infection, dysplasia, and cancer outcomes. We aimed to inform future research programs and the development of screening and care programs for Black MSM by identifying patterns in anal HPV infection, dysplasia, and cancer from the existing literature.

METHODS

This systematic review conforms to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.¹⁵ The purpose of the PRISMA statement is to improve the quality of reporting of systematic reviews and meta-analyses. The PRISMA statement is a living document consisting of a 27-item checklist and a 4-phase flow diagram. The checklist presents researchers with a standardized method for improving the quality of reporting in systematic reviews through a standardized method for reporting the title, defining the objectives, and presenting the search strategy, among other items. (The PRISMA checklist followed by study authors is reported in Table A, available as a supplement to this article at http://www.ajph.org.) The flow diagram provides researchers with a standardized method for reporting the reasons for the inclusion and exclusion of studies. We selected the PRISMA statement because of its utility in exploring other health disparities, such as the Robert Wood Johnson Foundation’s Finding Answers: Disparities Research for Change Program.^16–21 Although it conformed to the PRISMA guidelines, because outcomes reported in studies in this review varied and did not share a common health outcome, our systematic review did not meet current guidelines for submission to a systematic review protocol registry.

We completed the final search on March 30, 2014, and did not include any restriction on the earliest date of publication. Databases searched included MEDLINE, the Cochrane Review of Clinical Trials, Cumulative Index to Nursing and Allied Health Literature, and PsycINFO. We conducted a bibliographic review of previous reviews to identify additional relevant studies. (Appendix A, available as a supplement to this article at http://www.ajph.org, includes a description of our electronic database search.) This review does not have a published protocol and therefore was not registered.

Study Selection

The operational definition of anal pathology used during our search encompassed HPV, anal dysplasia, and anal cancer. Inclusion criteria were as follows:

1. Population included MSM;

2. Anal HPV, anal dysplasia, or anal cancer risk, prevalence, or incidence was defined as an outcome variable;

3. Race of study participants was reported in manuscript;

4. Reporting was quantitative;

5. Study was conducted in the United States; and

6. Study was published as a full manuscript in English.

We excluded studies that did not report quantitative data, such as those studies reporting qualitative description of anal HPV infection, dysplasia, and cancer, because such studies did not allow us to determine the racial group with the highest disease burden. We did not limit inclusion by study design and we used no time-frame criterion.

We compiled all eligible articles into a Microsoft Excel Database version 14.0.7128.5000 (Microsoft, Redmond, WA). Two research assistants conducted a first pass through the articles, sorting manuscripts as “eligible,” “ineligible,” or “uncertain” on the basis of the title and abstract. One of the study authors conducted a second pass. When there was a disagreement or when an article was classified as “uncertain,” the study authors reviewed the article a third time to determine study eligibility (Figure 1). We then sorted included manuscripts on the basis of anal HPV infection, dysplasia, and cancer outcome. Abstracted data included the study authors, study design, publication year, location, time period, overall study population, median age, race, and results.

FIGURE 1—

Study eligibility criteria used for analyzing anal human papillomavirus, dysplasia, and cancer (HDC) disparity for systematic review of literature up to March 2014: United States.

Note. MSM = men who have sex with men.

To compare anal pathology risk, prevalence, and incidence by race, we identified studies that stratified anal HPV infection, dysplasia, and cancer by race and abstracted those data from these studies. Finally, we identified a small number of studies that stratified anal HPV infection, dysplasia, and cancer results by race and sexual behavior to serve as the primary source of evidence for determining if racial disparity in anal HPV infection, dysplasia, and cancer exists between White and Black MSM.

Quality Assessment

Two reviewers (T. W. and C. B.- V.) determined study quality by using the Risk of Bias tool, which has been demonstrated to be reliable in evaluating studies assessing disease prevalence in a population.²² Although we have successfully used the Downs and Black checklist for systematic reviews of interventions to address health disparities,^21,23 we selected the Risk of Bias tool because of its utility in evaluating quality of observational studies. The quality score is calculated by rating each study across 2 domains including internal validity (5 items) and external validity (4 items). Selection and nonresponse bias are examined to determine external validity, and measurement bias is used to determine internal validity. An additional item is included to assess bias in the analysis. After discussion of differences in scores, we reached consensus on each article included in the review. (The modified Risk of Bias tool and the results for each study are reported in Appendix B and Tables B-1 and B-2, available as a supplement to this article at http://www.ajph.org.) As a quality-control measure recommended by the Cochrane Handbook for Systematic Reviews of Interventions,²⁴ the senior author (J. A. S.) rescored 10% of studies. The interrater agreement for quality score with the Risk of Bias tool was high (k = 0.89). We used linear regression to examine trends in quality score over time. We performed all analysis with Stata software version 12.0 (StataCorp LP, College Station, TX).

To determine whether a racial disparity in anal HPV infection, dysplasia, and cancer screening exists, we used the American Community Survey, a nationally representative population survey conducted by the US Census Bureau, to compare the number of Blacks and Whites in each study to the general population in the city where the study took place. We compared study populations with recruitment taking place either before 2006 or from 2006 or later with the American Community Survey 2005²⁵ or 2010²⁶ 1-year estimates, respectively. When the percentage of Blacks included in the study population was greater than or equal to the percentage of Blacks residing in the city in which the study took place, we determined that the study adequately represented the Black population in number in a particular city. When the percentage included in the study population was lower than in the general population, we determined that the study inadequately represented Blacks.

RESULTS

We identified a total of 25 articles published between 1992 and 2014 that reported anal HPV, dysplasia, or cancer and included race information of MSM study participants. Six of these studies stratified anal HPV infection, dysplasia, and cancer outcomes by race. Only 2 of the 25 eligible studies stratified outcomes by both race and sexual behavior, and allow for a fair comparison of anal HPV infection, dysplasia, and cancer rates between White and Black MSM. Thirteen (52%) were cohort studies; the remaining studies included 3 (12%) retrospective chart reviews, 7 (28%) cross-sectional studies, and 2 (8%) descriptive incidence studies. According to the Risk of Bias tool, the quality of the 25 studies ranged from 6 to 9 on a 10-point scale with a mean of 7.21. In linear regression analysis, we observed a significant trend of increasing study quality over time (r = 0.21; P = .02).

Anal HPV Infection, Dysplasia, and Cancer

Tables 1 through 4 summarize the results by anal HPV infection, dysplasia, and cancer for 25 studies reporting race of study participants and that include MSM in their study population. Salient differences between Whites and Blacks are described in detail in the paragraphs that follow. In addition, the findings from the 2 studies that stratified anal HPV infection, dysplasia, and cancer outcomes by race and sexual behavior are documented in detail.

TABLE 1—

Studies of Human Papillomavirus Among Men Who Have Sex With Men That Report Race (n = 8): Systematic Review of Literature up to March 2014, United States

Author and Year of Publication	Study Design	Location and Study Time Period	Study Population	Median Age, Years	Anal Pathologies	Racial/Ethnic Comparison	Results	Score
Critchlow et al.,27 1992	Standardized interview and specimen collection	Seattle, WA, 1987–1988	n = 145 100% MSM 17.9% HIV+ 82.06% HIV-	44	HPV types 6, 11, 16, 18, 31, 33, and 35	Black: 4% White: 88%	HIV-seropositive men were at increased risk for anal HPV DNA; seropositive asymptomatic men were 4.1 times more likely to have anal HPV DNA (95% CI = 1.1, 14.4).	7
Breese et al.,28 1995	Cross-sectional study	Denver, CO, 1989–1990	n = 209 100% MSM 44% HIV+	41	HPV types 6, 11, 16, 18, 31, 33, and 35	White: 93%	Anal HPV was associated with having an increased total lifetime sexual partners, HIV-positive serostatus (P < .001), and AIDS (P < .05).	6
Palefsky et al.,29 1998	Cohort study	San Francisco, CA, 1991–1994	n = 608 100% MSM 57% HIV+ 43% HIV-	43.5	HPV types 6, 11, 16, 18, 26, 31, 32, 33, 35, 39, 40, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 68, 69, 70, 73, AE2, Pap 155, Pap 291; HPV 2, 13, 34, 42, 57, 62, 64, 67, 72, and W13B	Black: 2% White: 91%	Anal HPV DNA was detected in 93% of HIV+ men and 61% of HIV- men; multiple HPV types were detected in 73% of HIV+ men and 23% of HIV- men. Lower CD4 levels were associated with group B DNA (more oncogenic HPV types) than group A DNA (P = .004).	7
Chin-Hong et al.,30 2004	Cross-sectional study	Boston, MA; Denver, CO; New York, NY; San Francisco, CA, 2001–2002	n = 1218 100% MSM 100% HIV-	37	HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68 and 73; HPV 6, 11, 53, 54, 55, 66, Pap 155, and Pap 291	Black: 6% White: 78%	HIV- MSM were found to have high rates of HPV across all age groups. HPV DNA was detected in 57% of study participants. HPV infection was associated with receptive anal intercourse (P < .001) and with having more than 5 sexual partners in past 6 months (P < .001).	8
Cranston et al.,31 2012	Cross-sectional study	Los Angeles, CA, 2005–2007	n = 316 67% MSM 100% HIV+	NA	HPV 6, 11, 16, 18, 26, 31, 32, 33, 35, 39, 40, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 68, 69, 70, 73, 82 variant, 83, 84; HPV 2, 13, 34, 42, 57, 62, 64, 67, 72, and 82	Black: 37% White: 20%	The prevalence of any HPV and high-risk HPV for the youngest age group was 100% and 68%, respectively. Use of drugs and alcohol was not associated with HPV infection. Blacks had the lowest percentage of HPV infection. Prevalence of any HPV, high-risk HPV, and multiple high-risk HPV was 87%, 59%, and 22% for Blacks, respectively.	8
Hernandez et al.,32 2013	Cohort study	San Francisco, CA, 1998–2001	n = 318 100% MSM 100% HIV+	42.5	HPV types 6, 11, 16, 18, 26, 31, 32, 33, 35, 39, 40, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 66, 68, 69, 70, 73, AE2, Pap 155, Pap 291; HPV 2, 13, 34, 42, 57, 62, 64, 67, 72, and W13B	Black: 2% White: 88%	Prevalence of anal HPV 16 was high among HIV-positive MSM. Having a higher total number of sexual partners (> 200) was associated with HPV 16 (RR = 1.6; 95% CI = 1.1, 2.4). Injection drug use associated with anal HPV 16 infection (RR = 1.5; 95% CI = 1.2, 1.9). White race was inversely associated with anal HPV 16 infection (RR = 0.53; 95% CI = 0.29, 0.95).	7
Glick et al.,33 2014	Prospective cohort study	Seattle, WA, 2009–2010	n = 94 100% MSM 4% HIV+ 96% HIV-	21	HPV types 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 62, 64, 66, 67, 68, 69, 70, 71, 72, 73, 81, 82, 83, 84, IS39, and CP6108	White: 60%	Number of lifetime male receptive anal sexual partners was associated with oncogenic HPV infection (OR = 1.16; 95% CI = 1.05, 1.28). Having greater than 2 receptive anal sexual partners was related to higher prevalence of HPV 16 or 18 (31% vs 6%). Increasing HPV immunization among all boys was recommended as approach to immunizing young MSM before critical first episode of receptive anal sex.	7
Wiley et al.,34 2013	Cross-sectional study	Baltimore, MD; Chicago, IL; Los Angeles, CA; Pittsburgh, PA, 2010–2011	n = 1262 100% MSM 46% HIV+ 54% HIV-	55	HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59; HPV types 26, 53, 66, 67, 68, 69, 70, 73, and 82; HPV types 6, 11, 40, 42, 54, 55, 61, 62, 64, 71, 72, 81, 83, 84, Is39, CP6108	Black: 17% White: 79%	HIV-infected men were more likely to have multitype HPV infections compared with non–HIV-infected men. For HIV-infected MSM, smoking cessation and monogamy are promising prevention strategies against HPV infections most related to anal cancer. Prevalence of group-2 high-risk HPVs was higher among non-Whites than Whites, indicating a possible difference by race.	8

Notes. CI = confidence interval; HIV+ = HIV-positive; HIV- = HIV-negative; HPV = human papillomavirus; MSM = men who have sex with men; NA = not available; OR = odds ratio; RR = relative risk ratio.

TABLE 2—

Studies of Anal Dysplasia Among Men Who Have Sex With Men That Report Race (n = 4): Systematic Review of Literature up to March 2014, United States

Author and Year of Publication	Study Design	Location and Study Time Period	Study Population	Median Age, Years	Anal Pathologies	Racial/Ethnic Comparison	Results	Score
Jay et al.,35 1997	Cohort study	San Francisco, CA, NA	n = 385 100% MSM 80% HIV+	42	HSIL, LSIL	Black: 1% White: 95%	Different grades of anal squamous intraepithelial lesions were similar to those in the cervix; 67% of biopsies showed LSIL and 26% showed HSIL.	6
Scott et al.,36 2008	Chart review	New Haven, CT, 2001–2004	n = 560 27% MSM 100% HIV+	44	AIN 1, 2, and 3; squamous cell carcinoma in situ; LSIL HSIL, ASCUS	Black: 49% White: 34%	In an urban HIV clinic setting, having an abnormal anal cytology was associated with White race (P = .03), homosexual orientation (P = .02), and lower CD4+ nadir (P = .005). Regardless of risk factors, anal cancer screening should be performed on all HIV-infected patients.	7
Mallari et al.,37 2012	Retrospective chart review	Rochester, NY, 2009–2010	n = 329 75% MSM 100% HIV+	49	AIN 1, 2, and 3; squamous cell carcinoma in situ; LSIL HSIL, ASCUS	Black: 18% White: 73%	Anal dysplasia is prevalent in HIV-positive persons regardless of risk factors outside of having HIV. Anal dysplasia prevalence was 66.5% in the high-risk group and 34.9% in the standard risk group, indicating that having HIV infection alone warrants annually screening all HIV-positive persons with anal cytology with high-resolution anoscopy.	6
Coromilas et al.,38 2014	Retrospective chart review	New York, NY, 2007–2012	n = 60 100% MSM 100% HIV+	21	Anal cytology (ASCUS, LSIL, HSIL)	Black: 55% White: 3.3%	In an urban population of HIV-infected young MSM, 53% had an abnormal anal cytological result. Anal cytology screening increased from 32% in 2008 to 81% in 2012; no risk factors were found to be associated with abnormal cytological result.	8

Notes. AIN = anal intraepithelial neoplasia; ASCUS = atypical squamous; HG-AIN = high-grade anal squamous intraepithelial neoplasia; HIV+ = HIV-positive; HIV- = HIV-negative; HPV = human papillomavirus; HSIL = high-grade squamous intraepithelial lesion; LSIL = low-grade squamous intraepithelial lesion; MSM = men who have sex with men; NA = not available.

TABLE 3—

Studies of Anal Cancer Among Men Who Have Sex With Men That Report Race (n = 3): Systematic Review of Literature up to March 2014, United States

Author, and Year of Publication	Study Design	Location and Study Time Period	Study Population	Median Age, Years	Anal Pathologies	Racial/Ethnic Comparison	Results	Score
Melbye et al.,39 1994	Descriptive incidence study	San Francisco–Oakland, CA; Detroit, MI; Atlanta, GA; Seattle, WA; CT; IA; NM; UT; HI; 1940–1989	n = 2448	55	Anal cancer	NA	Patterns of anal cancer indicated that anal cancer rates were higher in women than in men, among Blacks than Whites, and among city residents than residents of rural areas. Anal cancer incidence from 1973 to 1989 was lowest in White men (0.41 per 100 000) and highest among Black women (0.74 per 100 000).	8
Cress and Holly,40 2003	Descriptive incidence study	San Francisco, CA, 1995–1999	n = 2141 (anal cancer cases)	53	Anal cancer	NA	Increase in anal cancer rates from 1973 to 1999 can be attributed to MSM. Age-adjusted incidence of anal cancer was higher for women than men (AAIR 1.5 vs 1.2), but non-Hispanic Black men aged younger than 40 years had higher rates of anal cancer than women.	8
Crum-Cianflone et al.,41 2010	Prospective study	Baltimore, MD, 1985–2008	n = 4506 60% MSM 100% HIV+	28	Anal cancer	Black: 44% White: 44%	Among HIV-infected men, rates of anal cancer had increased 5 times from the pre-HAART (1985–1995) to post-HAART (1996–2008) era (RR =  5.0; 95% CI = 1.4, 18.4). Having HIV for > 15 y confers an anal cancer risk of 12 times (RR = 12.40; 95% CI = 4.06, 37.99). Black men have a lower rate of anal cancer than White men; 8 out of 1999 Black men had anal cancer and 11 out of 1992 White men had anal cancer.	9

Notes. AAIR = age-adjusted incidence rate; CI = confidence interval; HAART = highly active antiretroviral therapy; HIV+ = HIV-positive; MSM = men who have sex with men; NA = not available; RR = relative risk ratio.

TABLE 4—

Studies of Multiple Anal Human Papillomavirus, Dysplasia, and Cancer Outcomes Among Men Who Have Sex With Men That Report Race (n = 10): Systematic Review of Literature up to March 2014, United States

Author and Year of Publication	Study Design	Location and Study Time Period	Study Population	Median Age, Years	Anal Pathologies	Racial/Ethnic Comparison	Results	Score
Palefsky et al.,42 1994	Cohort study	San Francisco, CA, 1983–1984	n = 65 100% MSM 56.9% HIV+	39	HPV types 6, 11, 16, 18, 31, 33, 35; anal cytology (condyloma, AIN 1, 2, and 3)	Black: 0% White: 97%	Abnormal anal cytology was associated with HIV-positive serostatus with a CD4 count < 200/mm3 (P = .006) and smoking (P = .03).	6
Critchlow et al.,43 1995	Prospective cohort study	Seattle, WA, 1991–NA	n = 305 100% MSM 15% HIV+ 5.4% HIV-	35	HPV types 6, 11, 16, 18, 31, 33, 35; HG-AIN	White: 93%	HG-AIN developed in 5.4% of HIV- men and 15.2% of HIV+ men. HPV 16 or 18 was associated with development of HG-AIN for HIV+ men (RR = 3.0; 95% CI = 1.1, 7.8) and HIV- men (RR = 16.0; 95% CI = 2.0, 137.0).	7
Palefsky et al.,44 1997	Prospective study	San Francisco, CA, 1990–1991	n = 129 100% MSM 100% HIV+	41	HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52; anal cytology (ASCUS, LSIL, HSIL)	Black:4% White: 88%	Anal cytological abnormalities were found in 39% of MSM and HPV infection was found in 93% of men. Risk factors associated with abnormal anal cytology were HPV 16 or 18 infection (RR = 2.1; 95% CI = 1.2, 3.5) and intravenous drug use (RR = 1.8; 95% CI = 1.2, 2.7).	6
Friedman et al.,45 1998	Cohort study	Baltimore, MD, 1992–1994	n = 306 100% MSM 70% HIV+	NA	HPV types 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 62, 64, 66, 67, 68, 69, 70, 71, 72, 73, 81, 82, 83, 84, Pap 55, Pap 291, WB13B; anal cytology (ASCUS, SIL)	Black: 13%	HPV is more common in gay HIV+ men than in gay HIV- men. HPV types most associated with the development of anal cancer were 2 times more likely to be found in HIV+ men than in HIV- men.	7
Palefsky et al.,46 1998	Prospective cohort study	San Francisco, CA, 1991–1994	n = 623 100% MSM 55.5% HIV+	43.5	HPV types 6, 11, 16, 18, 26, 31, 33, 35, 39, 40, 42, 45, 51, 52, 53, 54, 55, 56, 58, 59, 61, 62, 64, 66, 67, 68, 69, 70, 71, 72, 73, 81, 82, 83, 84, Pap 155, Pap 291, wb13b; anal cytology and histology (ASCUS, LSIL, HSIL)	Black: 2% White: 91%	HSIL was more likely to develop in HIV+ men than in HIV- men (RR = 3.7; 95% CI = 2.6, 5.7). Lower CD4 levels, HPV infection, and HIV infection were associated with higher rates of HSIL among MSM.	7
Xi et al.,47 1998	Cohort study	Seattle, WA, 1989–1995	n = 589 100% MSM	NA	Anal carcinoma in situ; HPV type 16	Non-White: 11%	HPV 16 non–prototype-like was strongly associated with the development of anal carcinoma. Men with HPV 16 non–prototype-like variants were more likely to develop anal carcinoma in situ (RR = 3.2; 95% CI = 1.0, 10.3).	7
Kiviat et al.,48 1998	Prospective study	Seattle, WA, 1989–1995	n = 374 100% MSM 100% HIV+	34.3	HPV types 6, 11, 16, 18, 31, 33, 35, 39, and 45; HIV DNA, HIV RNA	Black: 5% White: 83%	Detection of anal–rectal HIV DNA was associated with anal–rectal inflammation (OR = 3.5; 95% CI = 1.8, 6.8) and anal HPV DNA (OR = 3.0; 95% CI = 1.4, 6.3).	7
Moscicki et al.,49 2003	Cross-sectional study	Chicago, IL; Los Angeles, CA; New York, NY; Mid-Atlantic (3); Southeast (6); 1996–1999	n = 348 (83 males) 70% MSM 70% HIV+ 30% HIV-	NA	HPV types 6, 11, 42, and 44; HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, and 58; anal cytology (ASCUS, LSIL, HSIL)	Black: 63% White: 14%	Abnormal anal cytology was more common among young men (41%) than young women, and HIV+ status was independently associated with anal HPV infection (OR = 6.5; 95% CI = 1.5, 11.9). 48% of young Black males were HPV-infected; 33% of young White males were HPV-infected. Screening should be considered among HIV-infected homosexual and bisexual adolescent boys.	9
Wilkin et al.,50 2004	Cross-sectional study	New York, NY, 2001–2002	n = 92 46% MSM 100% HIV+	41	HPV DNA, anal cytology (ASCUS, LSIL, HSIL), histology (AIN 1, 2, and 3)	Black: 36% White: 5%	In an urban HIV clinic, high-risk HPV DNA was detected in 61% of participants. A history of receptive anal intercourse was associated with the detection of high-risk HPV DNA (AOR = 7.1; 95% CI = 2.6, 20.0) and with abnormal cytological results (AOR = 10; 95% CI = 3, 36). Regardless of a history of receptive anal intercourse, all HIV-infected patients should be included in anal cancer screening programs.	8
Conley et al.,51 2010	Prospective cohort study	Denver, CO; Minneapolis, MN; Providence, RI; St. Louis, MO; 2004–2006	n = 621 61% MSM 100% HIV+	41	Anal cytology (ASCUS, LSIL, HSIL), HPV high-risk types and HPV low-risk types, rectal chlamydia and gonorrhea	Black: 15% White: 75%	HIV+ people with multiple HPV infections (OR = 1.24; 95% CI = 1.11, 1.41) or a nadir CD4 cell count < 50 (OR = 2.48; 95% CI = 1.02, 6.13) are more likely to have abnormal anal cytology.	9

Notes. AIN = anal intraepithelial neoplasia; AOR = adjusted odds ratio; ASCUS = atypical squamous; CI = confidence interval; HG-AIN = high-grade anal squamous intraepithelial neoplasia; HIV+ = HIV-positive; HIV- = HIV-negative; HPV = human papillomavirus; HSIL = high-grade squamous intraepithelial lesion; LSIL = low-grade squamous intraepithelial lesion; MSM = men who have sex with men; NA = not available; OR = odds ratio; RR = relative risk ratio.

Anal human papillomavirus infection.

We identified 8 studies that define HPV as the primary outcome and 2 of these reported outcomes by race (Table 1). Prevalence of HPV ranged from 8% to 70% among HIV-negative participants and 31% to 92% among HIV-positive participants.^28,30,32,33 One study found that White race was inversely associated with anal HPV 16 infection, a high-risk oncogenic HPV type.³² An analysis of HPV test results of study participants enrolled in the Multicenter AIDS Cohort Study highlighted a higher prevalence of group-2 high-risk HPV among non-Whites compared with Whites with White MSM showing a 1.3-times prevalence of group-2 high-risk HPV types.³⁴

Anal dysplasia.

Four studies defined anal dysplasia as a primary outcome and 2 of these studies reported outcomes by race. The association between HIV infection and MSM risk with an abnormal anal cytological result was corroborated by 2 studies.^36,37 Two chart reviews conducted in majority Black clinic populations yielded conflicting findings in terms of anal dysplasia by race. A chart review with a predominantly heterosexual sample (73%) found that White race was significantly associated with an abnormal anal cytology result.³⁶ Another chart review of young minority MSM (100% MSM) found that Black MSM had a higher prevalence of anal dysplasia than non-Black MSM (55% vs 44%), although this difference did not achieve statistical significance.³⁸

Anal cancer.

We identified 3 studies that defined anal cancer as a primary outcome and also reported outcomes by race. Anal cancer rates have increased temporally among HIV-infected men, with rates increasing by 500% among HIV-infected men before and after the start of the highly active antiretroviral therapy era.³⁹ In general, rates of anal cancer are consistently higher in Blacks than in Whites, and higher in women than in men. However, one study of anal cancer incidence in California that stratified the sample by age found that non-Hispanic Black men aged younger than 40 years had higher rates of anal cancer than women younger than 40 years.⁴⁰ No studies of anal cancer exclusively limit the study population to MSM; however, numerous studies indicate that MSM are disproportionately affected by anal cancer.

Multiple outcomes.

We identified 10 studies reporting multiple outcomes and only 1 of these reported outcomes by race. Human papillomavirus and cytological results were reported in 7 studies. Descriptive data from 1 study of minority adolescents indicated a higher percentage of HPV-infected Black males compared with White males (48% vs 33%).⁴⁹ Although only 1 study offered evidence regarding a possible difference in clinical findings of anal HPV or abnormal anal cytology by race, together these 10 studies demonstrate a strong link between HPV and the development of anal cancer.

Population and Settings

More than half of the studies (14; 64%) underrepresented Blacks in their study population compared with the general local population (see the box on page e43). This discrepancy ranged from 4% to 21% underrepresentation, with 2 of the 14 studies reporting only White participants. Six studies (24%) underrepresented Whites. The first study of anal HPV infection, dysplasia, and cancer in MSM to include a percentage of Black MSM representative of the Black population in the study city occurred in 2003.

Underreporting of Clinical Anal Human Papillomavirus, Dysplasia, and Cancer for Blacks and Whites: Systematic Review of Literature up to March 2014, United States

Studies Underreporting Whites (% Difference in Study Population and City Population)	Studies Underreporting Blacks (% Difference in Study Population and City Population)
Moscicki et al.49 (NAa)	Critchlow et al.43 (–4%)
Wilkin et al.50 (–39%)	Breese et al.28 (NA)b
Scott et al.36 (–38%)	Palefksy et al.42 (–7%)
Crum-Cianflone et al.41 (–26%)	Critchlow et al.27 (NA)b
Cranston et al.31 (–31%)	Jay et al.35 (–5%)
Coromilas et al.38 (–43%)	Palefksy et al.44 (–7%)
	Friedman et al.45 (–11%)
	Palefksy et al.29 (–5%)
	Palefksy et al.46 (–5%)
	Kiviat et al.48 (–3%)
	Chin-Hong et al.30 (–11%)
	Mallari et al.37 (–21%)
	Wiley et al.34 (–7%)
	Hernandez et al.32 (–5%)

Note. NA = not applicable. City population estimates extracted from 2005 and 2010 American Community Surveys.^25,26

^aBecause study included participants from 13 cities and 7 cities were not named, the percentage difference could not be determined. However, Whites were only 23% of the study population.

^bStudies only reported percentage of White participants.

Participants in eligible studies tended to be older and HIV-positive. The mean age across all studies was 42 years, with a range of 13 to 55 years. In 15 (60%) studies, the median age was older than 40 years. Only 3 (12%) studies reported a median age of participants younger than 24 years. The majority of studies included participants who were HIV-positive, with 10 studies (40%) consisting of only HIV-positive participants. One study included HIV-negative participants only.

Studies of anal HPV infection, dysplasia, and cancer were heavily concentrated on the coasts of the United States, with 14 (56%) studies taking place on the West Coast and 4 (16%) studies in the Northeast. Two (8%) studies were conducted in the Southeast and 5 (20%) were multisite studies occurring in multiple regions of the United States. No studies took place in the Midwest or Southwest.

Race

Eight studies described anal HPV infection, dysplasia, and cancer outcomes by race and included MSM in their sample^{31,34,36,38,40,41,49,52}; 2 of these further stratified their sample by sexual behavior and allowed for an anal HPV infection, dysplasia, and cancer comparison between White and Black MSM (Table 5). The 2 studies that stratified anal HPV infection, dysplasia, and cancer outcomes by race and sexual behavior both indicated higher rates of anal HPV infection, dysplasia, and cancer among Black MSM.^34,38 Findings from the Anal Health Study, a component of the Multicenter AIDS Cohort Study, indicated a 1.3 times lower prevalence of group-2 high-risk HPV types among White MSM in comparison with non-White MSM (P < .01).³⁴ Human papillomavirus genotyping was obtained from 1262 MSM at 4 study sites across the United States, with 218 (17%) Black MSM represented. In a smaller study in an urban HIV clinic in which Black MSM were more than 50% of the study population, anal cytology samples collected from 60 HIV-infected patients aged 18 to 25 years were consistent with findings from the Anal Health Study. Prevalence of abnormal anal cytology was 56.3% among Black MSM and 43.8% among White MSM,³⁸ although this did not achieve statistical significance.

TABLE 5—

Comparison of Anal Human Papillomavirus, Dysplasia, and Cancer, by Race: Systematic Review of Literature up to March 2014, United States

Anal Pathology	Elevated Risk for Blacks	Lower Risk for Blacks
HPV	Moscicki et al.49,a	Cranston et al.31,a
	Wiley et al.34,b
Dysplasia	Coromilas et al.38	Scott et al.36,a
Cancer		Crum-Cianflone et al.41,a

Notes. HPV = human papillomavirus. In the general population, Black men have a higher incidence of anal cancer than White men.^49,31,53

^aStudy participants include self-identified heterosexuals and men who have sex with men.

^bPrevalence of group-2 high-risk HPVs is higher among non-Whites than Whites. Blacks make up nearly 78% of non-White study participants.

The 6 other studies that reported race comparisons all included large numbers of self-identified heterosexuals and therefore offer limited generalizability. Three of these studies suggested a higher prevalence of anal HPV infection, dysplasia, and cancer among White MSM, with 1 study reaching statistical significance.^31,41,49 The only study of anal HPV infection, dysplasia, and cancer among adolescents to date indicates a higher prevalence of HPV among Blacks, but this did not achieve statistical significance.⁴⁹

DISCUSSION

We identified a general absence of Black MSM from studies that are important for understanding the factors that may increase risk for anal HPV infection, dysplasia, and cancer. Among studies that do include racial minority MSM, only 2 studies stratified the sample population by sexual behavior and race, which makes it difficult to draw definitive conclusions. Even from the limited number of studies reported in this review, however, several important points emerged. First, the proportion of Black study participants was less than the general Black population in the majority of studies. Second, the 2 studies that were stratified by race and sexual behavior reported a higher prevalence of anal HPV infection, dysplasia, and cancer in Black MSM, with 1 comparison achieving statistical significance. Third, very few of the identified studies described anal HPV infection, dysplasia, and cancer among Black MSM by age, which may become increasingly important as young Black MSM with HIV age and are at increased risk for anal cancer.

Underrepresentation of Black MSM is especially problematic in the case of anal cancer research for several reasons. First, findings from the Multicenter AIDS Cohort Study suggest that non-White MSM are more likely to be infected with group-2 high-risk HPV types than are White MSM. This finding is significant because group-2 high-risk HPV types are not included in current HPV vaccines. The finding that certain oncogenic HPV types might be more common among Black MSM mirrors a recent study of cervical HPV, which found Black women to have higher rates of oncogenic HPV types not targeted in current HPV vaccines than Whites.⁵ Second, Blacks experience higher rates of cancer than the general population.⁵⁴ Finally, Black MSM are more likely to be infected with HIV than any other risk group in the United States.⁹ Because HIV is an established risk factor for the development of anal cancer, anal cancer risk may be increased at the population level for Black MSM compared with other groups of MSM or other Black populations. The finding that Black MSM are underrepresented in studies of anal HPV infection, dysplasia, and cancer is similar to underparticipation of racial minorities in cancer clinical trial research^55,56 and HIV clinical trial research.⁵⁷

Limitations

Our review has several limitations. First, a limited representation of racial categories in the reporting of anal HPV infection, dysplasia, and cancer made it difficult to determine the presence or absence of a racial disparity in anal outcomes between Blacks and Whites. Second, younger MSM are largely absent from studies of anal HPV infection, dysplasia, and cancer, although this may be attributable to the epidemiology of anal cancer with usual age of onset increasing after the third decade.

Third, a few studies compared Whites to non-Whites, combining Blacks and Latinos into the same group. Given the distinctive sexual networks of Black MSM, which are mostly separate from the sexual networks of Latino and White MSM,^7,58,59 comparisons between White and Black MSM would be required to determine whether a disparity in anal HPV infection, dysplasia, and cancer exists. Finally, a number of studies included in the review did not differentiate between MSM and heterosexual men. Although we only reviewed studies that included MSM in the sample, a disparity in anal HPV infection, dysplasia, and cancer would best be determined from samples of MSM exclusively.

Conclusions

In summary, the broader absence of Black MSM from research on anal HPV infection, dysplasia, and cancer indicates the existence of a racial disparity in anal HPV infection, dysplasia, and cancer screening. Although 2 studies provide evidence suggesting that anal HPV infection, dysplasia, and cancer may be more prevalent among Black MSM, the absence of Black MSM from research on anal HPV infection, dysplasia, and cancer makes it difficult to determine the presence of a racial disparity in outcomes.

Existing research establishes a strong link between HIV infection and an increased risk for precursors to anal cancer^60,61; yet only 2 studies explored anal HPV infection, dysplasia, and cancer in Black MSM, which is the population with the highest rates of new infection. In addition, future reporting of anal HPV infection, dysplasia, and cancer data should differentiate Black MSM from other racial minorities in consideration of the unique within-group mixing patterns among Blacks compared with other racial groups. Future work should also seek to provide anal care to minority populations in numbers that reflect both the communities in which research takes place and the current burden of HIV in the US population. It is unclear whether lack of inclusion of Black MSM in anal HPV infection, dysplasia, and cancer research is a function of lack of access to clinical services among Black MSM. Providing Black MSM access to comprehensive anal care including screening for HPV-related anal dysplasia will help us determine best practices for this population and potentially mitigate poor anal health outcomes in this population.