Prevalence of and Risk Factors for Anal Human Papillomavirus Infection in a Sample of Young, Predominantly Black Men Who Have Sex With Men, Houston, Texas

Approximately two thirds of a sample of predominantly black men who have sex with men harbored human papillomavirus (HPV) genotypes in the anal canal that most commonly cause malignant and nonmalignant disease. It is important to increase the currently low HPV vaccine coverage in this population.

Abstract

Background

Young men who have sex with men (MSM) are at increased risk for human papillomavirus (HPV)–associated disease as a result of HPV infection. Our objective was to characterize the prevalence of high-risk anal HPV infection and factors associated with prevalence in a group of young, primarily black MSM in Houston, Texas.

Methods

MSM aged 18–29 years were recruited using a respondent-driven sampling method to study HIV and sexually transmitted disease transmission and risk. All engaged in peer-recruitment chains and self-collected anal exfoliated cells. Prevalence ratios assessed factors associated with high-risk HPV and HPV types in the 9-valent vaccine.

Results

Black race was reported by 87% of men. Slightly over one half (53%) were human immunodeficiency virus (HIV) positive. Approximately 75% of men had at least 1 high-risk HPV type, and 39% of HIV-positive men harbored HPV-16. Analysis that controlled for potential confounders revealed that only HIV infection was associated with high-risk HPV infection.

Conclusion

Black MSM would benefit from increased HPV vaccination efforts, owing to high rates of HPV infection, increased HPV disease, and low vaccination series completion rates in this population.

Despite the introduction of human papillomavirus (HPV) vaccination in the United States and its recommendation for use in females and males, the proportion of eligible boys and young men who have initiated and completed an HPV vaccine series is suboptimal [1–3]. For example, among young black men who have sex with men (MSM) recruited in 2 US cities in 2012–2014, only 12.4% reported receiving ≥ 1 dose of an HPV vaccine [4]. Given low uptake and completion of these vaccines that prevent infection with HPV genotypes that cause a large proportion but not all HPV-associated disease, men continue to be at risk for a variety of cancers and anogenital warts with an HPV infection etiology [5].

HPV-associated disease is not distributed equally by race. For example, black men have a higher incidence of and mortality from HPV-associated anal cancer [6, 7]; however, the burden of genital warts may be comparable among black and white MSM, although the differential access to healthcare by race may complicate comparisons [8].

Likewise, there is an uneven distribution of anal cancer incidence with regard to sexual orientation. Although there is poor collection of sexual orientation data in most US cancer registries [9], available data suggest that HIV-negative and HIV-positive MSM have an annual incidence of anal cancer that may be 5-fold and 50-fold higher, respectively, than that in the general population [10–12]. Most of these men lack protection from herd immunity conferred by female vaccination [13] and thus have been recommended for catch-up HPV vaccination by the Advisory Committee on Immunization Practices [3].

Few studies have focused on anal HPV infection or HPV-associated disease with regard to both race and sexual orientation [14]. One US study observed decreased anal HPV infection among white MSM as compared to MSM of other races and ethnicities [15], while a study of MSM recruited in the United States, Mexico, and Brazil found no difference in anal HPV persistence by race [16]. Another US study found that almost half of young black MSM exhibited HPV-associated disease [17], and another demonstrated a nonsignificantly increased prevalence of abnormal anal cytologic findings among young black MSM, compared with young MSM of other races and ethnicities [18]. A recent retrospective cohort of 2804 persons infected with HIV found that those of black race (59.4% of whom were MSM) had a similar prevalence of high-grade squamous intraepithelial lesions (HSIL) and a decreased risk of progression to HSIL, compared with white persons [19].

To further understand the epidemiology of anal HPV infection, we conducted HPV genotyping in a group of young, primarily black MSM in Houston, Texas. Our objective was to estimate the prevalence of HPV among these men, in addition to factors associated with prevalent HPV infection.

METHODS

Study Site and Participant Sampling

Men were recruited from 2014 to 2016 for the parent study, the Young Men’s Affiliation Project (YMAP), which examined their attendance history at risk and health venues and the HIV infection/sexually transmitted disease risk and prevention among young MSM in Houston and Chicago, Illinois [20]. Participants were recruited using a respondent-driven sampling (RDS) method [21], whereby young MSM “seed” participants were identified first from health-promoting and social venues. Then, each seed and successive waves of respondents were asked to refer up to 4 peers into the study by offering them vouchers. Each successful referral included a monetary incentive with a potential of up to $80 for participants. Our strategy of allowing 4 recruits was intended to overcome the tendency of networks of young MSM to be smaller and more segregated than networks of older MSM [22]. In Houston, study inclusion criteria were as follows: (1) an age of 16–29 years (inclusive), (2) male sex assigned at birth and identification as a male, (3) reported oral or anal sex with another male in the past year, (4) a residence in the Houston metropolitan area, and (4) plans to remain in their residential area for the following year. Funding restrictions limited the current HPV genotyping analysis to 139 men. We selected men in longer chains, for a total of 6 chains each comprising ≥7 persons (mean [SD], 24.5 ± 22.0 persons; range, 7–64 persons). A chain is a group of people who are recruited by a network-based link-tracing referral method. The protocol was approved by the Committee for Human Protections at the University of Texas Health Sciences Center at Houston.

Behavioral Data Collection

Interview measures were derived from a population-based survey of black MSM [23]. Interviews were conducted in person and were administered using a combination of computer-assisted self-interviewing and computer-assisted personal-interviewing techniques (Qualtrics, Provo, UT). In the computer-assisted personal interviews, the interviewer read questions from the computer and entered data. Questions collected data on demographic characteristics, substance use, social and sexual ties, and behavior with peers, in addition to participants’ affiliation with community organizations and businesses.

Biological Sample Collection and Testing

After being interviewed, YMAP participants then provided biological samples. Blood specimens were collected for HIV and syphilis testing, and then the men self-collected exfoliated cells from the anal canal [24]. In brief, men were instructed to insert a polyethylene terephthalate swab 3–4 cm into the anus and then rotate the swab as it was removed. The participant then inserted the swab into a capped tube of PreservCyt, which was snap frozen at −80ºC within 6 hours.

HIV testing of blood specimens included a Geenius HIV 1/2 Confirmatory test (Bio-Rad, Marnes-la-Coquette, France) and HIV RNA viral load quantification (Cobas AmpliPrep/Cobas TaqMan HIV-1 test kit, version 2.0; Roche Molecular Diagnostics, Pleasanton, CA). For syphilis screening, all participants underwent fluorescent treponemal antibody (FTA) testing (IFA [Immunofluorence Assay] Fluorescent Treponemal Antibody-Absorption Test System; Zeus Scientific, Branchburg, NJ), followed by a rapid plasma reagin (RPR) test (Macro-Vue RPR Card Test Kit; BD Diagnostics, Franklin Lakes, NJ) if results of the FTA test were positive. Participants were considered to have syphilis if the RPR titer was ≥ 1:4 and FTA test results were positive.

All samples were analyzed for HPV DNA and β-globin, as described elsewhere [25]. In brief, to identify HPV DNA, laboratory staff used the polymerase chain reaction (PCR) consensus primer system (PGMY 09/11) to amplify a fragment of the HPV L1 gene. HPV genotyping was then conducted on all samples by use of DNA probes labeled with biotin to detect the following 36 HPV types: HPV-6, -11, -16, -18, -26, -31, -33, -34, -35, -39, -40, -42, -44, -45, -51 through -54, -56, -58, -59, -61, -62, -66 through -73, -81 through -84, and -89 [26]. Accuracy and potential contamination were assessed using nontemplate-negative controls and CaSki DNA–positive controls. Of 139 men who provided biological specimens and behavioral data, 135 were β-globin or HPV genotype positive.

Statistical Analysis

Of 135 men with adequate specimens for genotyping, a specimen was defined as positive for HPV if it was positive for any of 36 HPV types. The group of high-risk HPV types was defined as HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, and -68, regardless of the presence of low-risk types. The group of any low-risk types comprised any of the remaining 23 HPV types in the array, regardless of the presence of high-risk types. The group of only low-risk types comprised any of the remaining 23 HPV types in the array in the absence of high-risk types. For any of the 36 types, a sample that was found to be positive by PCR but not by genotyping was labeled as positive for an unclassified HPV type.

We estimated prevalence for HPV groups and individual genotypes, using Gile’s sequential sampling (RDS-SS) estimators, which are weighted by self-reported peer network size and assume sampling without replacement [27]. We assessed peer network size by asking participants for the number of young MSM aged 16–29 years they know by name in Houston. This question was preceded by 2 priming questions: one about the number of people they know in the local area, more generally, and another about the number of those who are MSM. Our reported RDS prevalence estimates (with confidence intervals [CIs]) were generated by the RDS program [28] in the R statistical environment. We also computed RDS-unadjusted prevalence estimates, which were, in general, not substantially different than the RDS-adjusted estimates. They are included in Supplemental Table 1.

For assessment of factors associated with anal HPV infection, 2 men were missing information about their HIV status, leaving 133 men available for analysis. We used the χ² and Fisher exact tests to assess differences in HPV prevalence by demographic and behavioral characteristics. To assess factors associated with high-risk HPV and the group of HPV genotypes covered by the 9-valent vaccine (HPV-6, -11, -16, -18, -31, -33, -45, -52, and -58), prevalence ratios and 95% CIs were estimated using Poisson regression with a robust variance estimator [29, 30]. Variables with a P value of < .25 on a score test in bivariate analysis were included in multivariable modeling as long as they were not intermediate variables [31]. Specifically, the HIV load was assumed to be in the causal pathway between HIV infection and anal HPV infection and was therefore not included in multivariable modeling. Potential confounders were determined using directed acyclic graphs and prior literature [32]. Independent risk factors for the outcome were identified using a backward-elimination method. Variables with a P value of > .05 on a score test were removed until a final set of factors remained. Given ongoing development of techniques that use RDS weights in multivariable analysis [33], we report prevalence ratios without RDS weights; however, RDS-weighted estimates for univariate associations between factors and anal HPV infection are included in Supplementary Table 2. These estimates incorporate RDS adjustments that approximate the inclusion probability as inversely proportional to the peer network size, which represents the degree based on self-reported personal network size [34]. Regression analysis was conducted with SAS 9.4 (SAS Institute).

RESULTS

A majority of men were 21–29 years old (Table 1). A total of 87% of men reported their race/ethnicity as black, while 55% of men reported at least some college attendance. Most identified as gay (82%), while 14% identified as bisexual. About one third of men reported being in a relationship; 29% of men reported sex with 0 or 1 person in the past 6 months, and 26% reported sex with ≥6 men in the past 6 months. A total of 23% of participants reported being homeless in the past 12 months, 53% were HIV positive, and 27% had syphilis. Slightly fewer than 10% of men reported a prior diagnosis of anal or genital warts.

Table 1.

Characteristics and Prevalence of Anal Human Papillomavirus (HPV) Infection Among 133 Young Men Who Have Sex With Men, Houston, Texas, 2014–2016

Factor	No. (%)	Prevalence (95% CI)a
		Any High-Risk Type	Any 9-Valent Vaccine Type
Age, y
18–20	16 (12.0)	0.75 (.54–.96)	0.63 (.38–.87)
21–25	63 (47.4)	0.68 (0.57 -0.80)	0.70 (0.58 -0.81)
26–29	54 (40.6)	0.69 (0.56 -0.81)	0.63 (0.50 -0.76)
Raceb
Black	113 (86.9)	0.68 (0.59 -0.77)	0.65 (0.57 -0.74)
White	9 (6.9)	0.89 (0.68 -1.00)	0.78 (0.50 -1.00)
Multiracial, other	8 (6.2)	0.63 (0.29 -0.96)	0.50 (0.15 -0.85)
Ethnicity
Hispanic	17 (12.8)	0.65 (0.42 -0.88)	0.59 (0.35 -0.83)
Non-Hispanic	116 (87.2)	0.70 (0.61 -0.78)	0.67 (0.59 -0.76)
Sexual orientation
Gay	109 (82.0)	0.69 (0.60 -0.78)	0.68 (0.59 -0.77)
Bisexual	18 (13.5)	0.67 (0.45 -0.89)	0.56 (0.32 -0.79)
Heterosexual/other	6 (4.5)	0.83 (0.53 -1.00)	0.67 (0.28 -1.00)
Education duration, y
0–12	60 (45.1)	0.73 (0.62 -0.85)	0.72 (0.60 -0.83)
≥13	73 (54.9)	0.66 (0.55 -0.77)	0.62 (0.50 -0.73)
In relationship with main sex partner
Yes	45 (34.1)	0.69 (0.55 -0.83)	0.62 (0.48 -0.77)
No	87 (65.9)	0.70 (0.60 -0.80)	0.69 (0.59 -0.79)
Homelessness
Never homeless	103 (77.4)	0.67 (0.58 -0.76)	0.62 (0.53 -0.72)
Homeless in past 12 mo	30 (22.6)	0.77 (0.61 -0.92)	0.80 (0.65 -0.95)
HIV test result in study
Positive	71 (53.4)	0.79 (0.69 -0.88)	0.82 (0.73 -0.91)
Negative	62 (46.6)	0.58 (0.46 -0.71)	0.48 (0.36 -0.61)
HIV load, copies/mLb,c
1–399	25 (36.8)	0.88 (0.75 -1.00)	0.88 (0.75 -1.00)
400–10000	12 (17.6)	0.83 (0.62 -1.00)	0.83 (0.62 -1.00)
>10000	31 (45.6)	0.71 (0.55 -0.87)	0.77 (0.63 -0.92)
Self-reported physician-diagnosed anogenital warts
Yes	13 (9.8)	0.54 (0.26 -0.81)	0.69 (0.44 -0.95)
No	120 (90.2)	0.71 (0.63 -0.79)	0.66 (0.57 -0.74)
Syphilis test result during studyb,d
Syphilis	35 (26.9)	0.69 (0.53 -0.84)	0.66 (0.50 -0.82)
Latent T. pallidum infection	17 (13.1)	0.65 (0.42 -0.88)	0.59 (0.35 -0.83)
Negative	78 (60.0)	0.71 (0.60 -0.81)	0.68 (0.57 -0.78)
Sex partners in past 6 mo, no.e
0–1	38 (28.6)	0.66 (0.51 -0.81)	0.63 (0.48 -0.79)
2–5	61 (45.9)	0.67 (0.55 -0.79)	0.62 (0.50 -0.75)
≥6	34 (25.6)	0.76 (0.62 -0.91)	0.76 (0.62 -0.91)

χ² and Fisher exact tests for the association between factors and high-risk type and/or 9-valent type yielded P values of >.05 except for HIV status and high-risk types (P = .014), HIV status and 9-valent types (P < .0001), HIV load and high-risk types (P = .030), and HIV load and 9-valent types (P < .001).

Abbreviations: CI, confidence interval; HIV, human immunodeficiency virus.

^aSee the body text for HPV types classified as high risk and those included in the 9-valent vaccine.

^bData are missing on race for 3 individuals, on HIV load for 3 individuals, and on syphilis test results for 3 individuals.

^cData are for HIV-positive individuals only.

^dA rapid plasma reagin (RPR) titer of ≥1:4 defined syphilis, and an RPR titer of <1:4 defined latent Treponema pallidum infection.

^eMean ± SD, 4.8 ± 5.8 sex partners; range, 0–40 sex partners.

After RDS adjustment, high-risk HPV was detected in 93% of HIV-positive men and 51% of HIV-negative men (Table 2). Most HIV-positive men had evidence of ≥1 HPV type in the 9-valent vaccine (92%), while only 32% of HIV-negative men harbored a 9-valent type; however, 0% of HIV-positive or HIV-negative men harbored all 9 types. For HIV-positive men, the most common genotypes were HPV-16 (prevalence, 39%), HPV-59 (38%), HPV-18 (37%), HPV-45 (34%), and HPV-35 (31%). Distribution of genotypes among HIV-negative men was quite different, with the 5 most prevalent genotypes being HPV-53 (prevalence, 19%), HPV-83 (18%), HPV-68 (17%), HPV-61 (15%), and HPV-51 (13%).

Table 2.

Respondent-Driven Sampling–Adjusted Prevalence of Anal Human Papillomavirus (HPV) Infection, Overall and by Human Immunodeficiency Virus (HIV) Status, Among Young Men Who Have Sex With Men, by HPV Genotype(s), Houston, Texas, 2014–2016

HPV Genotype(s)	Overall (n = 135)a		HIV Positive (n = 71)		HIV Negative (n = 62)
	No.	Prevalence (95% CI)	No.	Prevalence (95% CI)	No.	Prevalence (95% CI)
Any type	116	0.86 (.77–.95)	67	0.97 (.92–1.01)	47	0.70 (.51–.88)
Any high-risk type	94 0.76 (0.65 - 0.88)		56 0.93 (0.88 - 0.99)		36 0.51 (0.32 - 0.70)
Any low-risk type	98 0.77 (0.66 - 0.88)		59 0.87 (0.78 - 0.95)		37 0.60 (0.40 - 0.79)
Only low-risk type	22 0.10 (0.02 - 0.18)		11 0.04(0.00 - 0.07)		11 0.19 (0.05 - 0.34)
Multiple types	100 0.74 (0.62 - 0.86)		60 0.93 (0.87 - 0.99)		38 0.47 (0.28 - 0.66)
Both HPV-16 and -18	8 0.12 (0.01 - 0.24)		8 0.24 (0.03 - 0.45)		0	…
All 4-valent vaccine typesb	1 0.00 (0.00 - 0.01)		1 0.01 (0.00 - 0.02)		0	…
All 9-valent vaccine typesc	0	…	0	…	0	…
Either HPV-16 or -18	35 0.32 (0.18 - 0.47)		25 0.52 (0.30 -0.74)		9 0.13 (0.01 - 0.24)
Any 4-valent vaccine type	55 0.45 (0.30 - 0.60)		40 0.66 (0.47 -0.85)		14 0.16 (0.02 - 0.30)
Any 9-valent vaccine type	90 0.66 (0.52 - 0.80)		58 0.92 (0.81 -1.02)		30 0.32 (0.15 - 0.49)
High-risk type d
16	25 0.23 (0.10 - 0.35)		19 0.39 (0.18 - 0.61)		6 0.07( 0.00 - 0.18)
18	18 0.22 (0.08 - 0.36)		14 0.37 (0.13 - 0.60)		3 0.06 (0.02 - 0.10)
31	12 0.11 (0.00 - 0.22)		7 0.10 (0.00 - 0.26)		4 0.05 (0.00 - 0.13)
33	7 0.06 (0.01 - 0.10)		5 0.08 (0.00 - 0.16)		2 0.06 (0.04 - 0.07)
35	17 0.23 (0.07 - 0.38)		12 0.31 (0.07 - 0.55)		4 0.12 (0.00 - 0.27)
39	15 0.13 (0.03 - 0.23)		10 0.21 (0.03 - 0.40)		5 0.06 (0.00 - 0.17)
45	19 0.22 (0.10 - 0.35)		12 0.34 (0.14 - 0.55)		6 0.07 (0.00 - 0.13)
51	22 0.23 (0.10 - 0.36)		14 0.26 (0.06 - 0.45)		7 0.13 (0.00 - 0.29)
52	13 0.09 (0.00 - 0.19)		8 0.13 (0.00 - 0.32)		5 0.05 (0.00 - 0.13)
58	21 0.16 (0.04 - 0.27)		15 0.23 (0.02 - 0.44)		6 0.09 (0.04 - 0.15)
59	28 0.28 (0.14 - 0.41)		20 0.38 (0.17 - 0.60)		7 0.06 (0.00 - 0.19)
68	21 0.20 (0.06 - 0.34)		11 0.20 (0.00 - 0.41)		8 0.17 (0.01 - 0.33)
Low-risk type
6	22 0.14 (0.03 - 0.25)		16 0.17 (0.02 - 0.33)		6 0.04 (0.00 - 0.13)
11	12 0.12 (0.01 - 0.23)		10 0.19 (0.00 - 0.41)		2 0.06 (0.04 - 0.08)
42	14 0.13 (0.02 - 0.25)		9 0.24 (0.03 - 0.45)		4 0.01 (0.00 - 0.02)
44	9 0.10 (0.00 - 0.20)		7 0.16 (0.00 - 0.35)		2 0.05 (0.04 - 0.07)
53	21 0.17 (0.05 - 0.28)		10 0.17(0.00 - 0.36)		11 0.19 (0.03 - 0.35)
54	8 0.07 (0.00 - 0.15)		2 0.01 (0.00 - 0.02)		5 0.06 (0.00 - 0.14)
61	17 0.15 (0.03 - 0.27)		12 0.13 (0.00 - 0.29)		4 0.15 (0.00 - 0.31)
62	20 0.16 (0.05 - 0.26)		14 0.17 (0.01 - 0.33)		6 0.04 (0.00 - 0.12)
66	19 0.11 (0.01 - 0.21)		13 0.10 (0.00 - 0.24)		5 0.07 (0.02 - 0.12)
73	9 0.07 (0.02 - 0.12)		6 0.07 (0.00 - 0.13)		3 0.04 (0.00 - 0.11)
81	14 0.20 (0.06 - 0.33)		10 0.17 (0.02 - 0.31)		3 0.13 (0.00 - 0.29)
82	9 0.04 (0.01 - 0.07)		7 0.07 (0.01 - 0.14)		2 0.00 (0.00 - 0.01)
83	16 0.17 (0.05 - 0.29)		7 0.11 (0.00 - 0.26)		8 0.18 (0.01 - 0.35)
84	22 0.16 (0.05 - 0.27)		14 0.16 (0.01 - 0.30)		6 0.12 (0.01 - 0.24)
89	19 0.17 (0.05 - 0.30)		11 0.23 (0.02 - 0.44)		7 0.08 (0.00 - 0.19)

^aData on HIV status were missing for 2 participants.

^bHPV-6, -11, -16, and -18.

^cHPV-6, -11, -16, -18, -31, -33, -45, -52, and -58.

^dGenotypes with a total prevalence of ≤0.05 and that are not included in the 9-valent vaccine (ie, HPV-56, -26, -34, -40, -67, and -69 through -72) are not shown.

In univariate analysis, only HIV status was statistically significantly associated with high-risk types and 9-valent types (Table 3). Men who were HIV positive were 69% more likely to harbor a 9-valent HPV type as compared to men who were HIV negative (prevalence ratio, 1.69; 95% CI, 1.28–2.23). In multivariable analysis and after adjustment for the continuous forms of age and number of sex partners in the past 6 months, only HIV status was associated with high-risk HPV types, with HIV-positive men 37% more likely to harbor a high-risk HPV genotype (adjusted prevalence ratio, 1.37; 95% CI, 1.07–1.75) and 73% more likely to harbor at least 1 genotype in the 9-valent vaccine (adjusted prevalence ratio, 1.73; 95% CI, 1.31–2.29). No other factors were independently associated with anal HPV infection (data not shown).

Table 3.

Univariate Analysis of Factors Associated With High-Risk and 9-Valent Vaccine Human Papillomavirus (HPV) Genotypes Among 133 Young Men Who Have Sex With Men, Houston, Texas, 2014–2016

Factor	Prevalence Ratio (95% CI)a
	Any High-Risk Type	Any 9-Valent Vaccine Type
Age, y
18–20	1.09 (0.78–1.53)	0.99 (0.64–1.53)
21–25	1.00 (0.78–1.28)	1.11 (0.85–1.44)
26–29	1.0	1.0
Race
Black	1.0	1.0
White	1.30 (1.00–1.70)	1.19 (0.82–1.73)
Multiracial/other	0.92 (0.53–1.59)	0.76 (0.38–1.55)
Ethnicity
Hispanic	1.0	1.0
Non-Hispanic	1.08 (0.74–1.56)	1.14 (0.75–1.74)
Sexual orientation
Gay	1.0	1.0
Bisexual	0.97 (0.68–1.38)	0.82 (0.53–1.26)
Heterosexual/other	1.21 (0.83–1.77)	0.98 (0.55–1.75)
Education duration, y
0–12	1.12 (0.89–1.40)	1.16 (0.91–1.48)
≥13	1.0	1.0
In relationship with main sex partner
Yes	0.98 (0.77–1.25)	0.90 (0.69–1.18)
No	1.0	1.0
Homelessness
Never homeless	0.87 (0.69–1.11)	0.78 (0.61–0.98)
Homeless in past 12 mo	1.0	1.0
HIV test result in study
Positive	1.36 (1.06–1.73)	1.69 (1.28–2.23)
Negative	1.0	1.0
HIV load, copies/mL
1–399	1.24 (0.95–1.62)	1.14 (0.90–1.44)
400–10000	1.17 (0.84–1.65)	1.08 (0.78–1.48)
>10000	1.0	1.0
Self-reported physician-diagnosed anogenital warts
Yes	0.76 (0.45–1.27)	1.05 (0.72–1.54)
No	1.0	1.0
Syphilis test result during studyb
Syphilis	0.97 (0.75–1.27)	0.97 (0.73–1.28)
Latent T. pallidum infection	0.92 (0.63–1.34)	0.87 (0.57–1.33)
Negative	1.0	1.0
Sex partners in past 6 mo, no.
0–1	0.86 (0.64–1.16)	0.83 (0.61–1.12)
2–5	0.88 (0.68–1.14)	0.81 (0.62–1.07)
≥6	1.0	1.0
Sex partners in past 6 mo (continuous), no.
Square root transformed	1.01 (0.90–1.13)	1.06 (0.96–1.16)

Abbreviations: CI, confidence interval; HIV, human immunodeficiency virus.

^aSee the body text for HPV types classified as high risk and those included in the 9-valent vaccine.

^bA rapid plasma reagin (RPR) titer of ≥1:4 defined syphilis, and an RPR titer of <1:4 defined latent Treponema pallidum infection.

DISCUSSION

We detected at ≥1 HPV genotype from the 9-valent vaccine in 32% of HIV-negative men and 92% of HIV-positive men; thus, as also observed in Chicago and Los Angeles among predominantly young Latino and non-Hispanic white MSM and transgender women recruited in sexual health clinics [4, 35], these young, predominately black MSM recruited through peer networks would benefit from 9-valent vaccination as recommended by the Advisory Committee on Immunization Practices for all MSM through age 26 years. HPV genotypes in the 9-valent HPV vaccine are uniquely predisposed to cause disease, and thus the high prevalence of infection with any one of these types signals the high risk of these young MSM for HPV-associated anogenital disease and later invasive malignancies.

Given the commonality of HPV types in the anal canal for these young men, our observations also support continued vaccination of adolescent males before sexual debut. It also follows that the high prevalence among these young men supports continued research for optimal HPV-associated disease screening practices among MSM since most of these young men will likely get little or no protection from HPV vaccines during their lives.

HIV-positive status is known to be independently associated with anal HPV prevalence [36], as observed in the current study, where HIV-positive status was strongly associated with high-risk genotypes and 9-valent vaccine genotypes after adjustment for potential confounders. While a lower number of sex partners was nonsignificantly associated with decreased prevalence in these men, no demographic or behavioral factor other than HIV status was independently associated with HPV prevalence.

MSM who reported a white race had a higher crude prevalence of anal HPV infection than black MSM; however, 95% CIs of the prevalence estimates largely overlapped, possibly as a result of the small number of white men (9) in the sample. The point estimate may also be due to random variability, although white MSM often report a higher number of unprotected anal intercourse partners than black MSM [37]. Such may also be the case among these men: white MSM reported a mean and median of 5.9 and 3 total sex partners, respectively, in the past 6 months, while black MSM reported a mean and median of 4.3 and 3 total sex partners, respectively, in the past 6 months. Nevertheless, race was not associated with anal HPV infection after adjustment for age, number of sex partners, and HIV status.

Our observed prevalence of any 9-valent vaccine type with RDS adjustment (92% among HIV-positive men and 32% among HIV-negative men) is somewhat comparable to that in the Chicago and Los Angeles convenience sample, which observed a prevalence for any 9-valent vaccine type of 83% and 46% for HIV-positive and HIV-negative participants (aged 18–26 years), respectively [35]. HPV-16 is responsible for the large majority of anal cancers, and the current study’s HPV-16 prevalence of 39% among HIV-positive MSM is also comparable to the Chicago and Los Angeles study (36%) and a second study of HIV-positive MSM in Montreal (38%) [38]. The HPV-16 prevalence we detected among HIV-positive men is also comparable to that in a study of 54 primarily black HIV-positive men, where 33% had anal HPV-16 infection [17].

In a study of 203 HIV-positive MSM, the most common high-risk types among mostly white participants were HPV-16, HPV-51, HVP-33, HPV-68, and HPV-39 [39]. In the current study, which involved mostly black MSM with HIV, HPV-16 was also the most common high-risk type. While HPV-16 and HPV-18 cause the large majority (80%–90%) of HPV-associated anal cancers [40, 41], the high prevalence of other high-risk types in the current study (ie, HPV-59, HPV-45, and HPV-35) underscores the need to be attentive to disease risk associated with these types.

Funding restrictions limited the current analysis to 139 men recruited through respondent-driven sampling and chosen for HPV genotyping if the men were connected to each other in chains of ≥ 7 persons. There are challenges to using RDS methods with regard to obtaining valid estimates of disease prevalence and accounting for RDS assumptions in analyses [42]. In particular, recruitment of young MSM poses challenges in terms of generating an unbiased representative sample, owing to segmentation of recruitment networks by race and ethnicity [22].

Also notable is the prevalence of a self-reported history of anogenital warts (10%) and study-determined syphilis (27%) in these men. It is possible that this study recruited men at particularly high risk for sexually transmitted infections, including HPV infection. Men were not asked about HPV vaccination status, although the proportion vaccinated is likely very low, based on recently published estimates [4]. In addition, the use of face-to-face interviewing to collect some sexual behavior data may have magnified social desirability bias in those data.

In summary, we found that two thirds of these men had ≥1 HPV type represented in the 9-valent HPV vaccine. While this study was not designed to assess the burden of HPV-associated anal dysplastic lesions, we believe black MSM would benefit from HPV vaccination, based on an overall HPV-16 prevalence of 23% and black men’s increased risk for HPV-associated anal cancer [6]. HPV vaccination has resulted in dramatic reductions in disease in populations with adequate vaccine coverage [43]; thus, increasing vaccine coverage in populations with high rates of disease and low vaccine uptake, such as young black MSM [4, 44, 45], should be a priority [46].

Supplementary Data

Supplementary materials are available at The Journal of Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.

Notes

Acknowledgments. We thank the men who volunteered biological specimens and data, the YMAP staff who collected the data, and the staff of Dr Anna Giuliano’s laboratory.

Financial support. This work was supported by the National Institute of Mental Health (grant 1R01MH100021 to the Young Men’s Affiliation Project of HIV Risk and Prevention Venues) and the National Institute on Drug Abuse (grant 1R01DA039934) to the HIV intervention models for criminal justice involved substance-using Black MSM, National Institutes of Health; and the State of Texas, via startup funds to the School of Public Health, UTHealth, and the Center for Health Promotion and Prevention Research at UTHealth.

Potential conflicts of interest. A. G. N. has a contract with Merck (MISP #56569) that will supply free Gardasil 9 vaccine for another study to test a vaccine intervention. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.