A Sequential Mixed-Methods Study of Factors Associated with Low High-Resolution Anoscopy Completion in Transgender Women with Abnormal Anal Cytology

Abstract

In a cohort of transgender women (TGW) with abnormal anal cytology (AAC) in Washington, DC, we determined the rates of and factors associated with completion of high-resolution anoscopy (HRA). This mixed-methods study used a sequential study design. In an academic-community clinic, we recruited TGW who provided blood samples, anal swabs for anal cytology, and completed surveys. For the quantitative phase of this study, we used χ² test to compare factors associated with HRA completion among TGW with AAC. From that cohort, we used purposive sampling to recruit 16 TGW for qualitative interviews, based on their HRA completion status. We used thematic analysis to analyze the qualitative data. Of 75 TGW, 36 (48%) had AAC, 32 (43%) were referred to HRA, and 15 (20%) completed HRA. HRA completion was associated with being employed (75% vs. 25%; p = 0.01) in the quantitative phase, and low socioeconomic status (SES) was considered a barrier to completing HRA in the qualitative phase. HRA completion was associated with suppressed HIV (67% vs. 18%; p = 0.01) in the quantitative phase. In the qualitative phase, trans-affirming care, receptive anal sex, and engaging in sex work were identified as motivators to completing HRA. In a population of TGW, we found high rates of AAC and low rates of HRA completion. Interventions targeting this gap should address barriers associated with low SES and HIV viremia in TGW. Trans-affirming care and the impact on anal sexual practices should be used as motivators to engage TGW in anal cancer screening.

Introduction

Transgender women (TGW) are disproportionately affected by anal cancer with a prevalence 5.5 times higher than cisgender individuals. ¹ This disparity is linked to a high prevalence of human papilloma virus (HPV) ² —the main cause of anal cancer—and HIV ³ —which potentiates HPV infection and HPV-related dysplasia. In 2024, the first guidelines dedicated to anal cancer screening were released and recommended that TGW with or without HIV get screened for anal cancer by anal cytology and/or HPV testing through clinician-collected anal swabs. ^4,5 Those with abnormal results and/or HPV16 infection are referred to high-resolution anoscopy (HRA), a procedure that allows the detection and ablation of high-grade squamous intraepithelial lesions (HSIL)—the precursor to anal cancer. ⁴ Such treatment is the only method available for secondary prevention of anal cancer and can reduce the risk of developing anal cancer by 60% as demonstrated by the Anal Cancer–HSIL Outcomes Research (ANCHOR) trial. ⁶

The anal cancer screening cascade includes multiple components: (1) screening those who are at risk for anal cancer with anal swabs, (2) referring those with abnormal screening to HRA, (3) completing HRA among those who are referred, and (4) treating those with HSIL via HRA. ⁷ Challenges currently facing this continuum include low adoption of anal cancer screening in those at risk, lack of knowledge among providers and patients of this cascade, stigma facing anal cancer screening, and a dearth of providers skilled in HRA. ⁸ Semi-structured interviews with 58 cisgender men who have sex with men (MSM) in Miami identified patient embarrassment and lack of physician recommendation as main barriers to engaging in anal cancer screening. ⁹ Similarly, focus groups of 19 health care advocates working with MSM in Los Angeles considered stigma, and physical and psychological discomfort with anal cancer screening as barriers to completing this screening. ¹⁰ Further, in a group of people living with HIV (LWH), the lack of self-perceived anal cancer risk, and low awareness of screening were deterrents to completing anal cancer screening. ¹¹ Nonetheless, existing studies have not examined barriers to the latter half of this screening continuum (linkage and completion of HRA) among TGW with abnormal anal cytology (AAC). Therefore, using a mixed-methods approach, we aimed to examine rates of and factors associated with HRA completion in a cohort of TGW.

Methods

Study design and participants

This mixed method study used a sequential study design in which the quantitative data collection was used to examine rates of and factors associated with HRA completion. The quantitative phase was followed by qualitative interviews to elicit additional information on factors contributing to HRA completion.

In the quantitative phase, we analyzed data from “Prospective Analysis of Transgender Individuals At-Risk and Living with HIV to Understand the Impact of Integrating HIV Treatment and Prevention into Transgender Care Utilizing Hormone Therapy (PATCH),” a natural history study of participants who were 18 years or older and identified as transgender, non-binary, or a gender identity different than their sex assigned at birth. ¹² This study was conducted in an academic clinic providing gender-affirming care and treatment and prevention of HIV and sexually transmitted infections (STI), embedded in a community-based organization that provides services to transgender people. Participants were recruited between April 2021 and May 2023. Participants included in the quantitative analysis were all assigned male at birth. While acknowledging the diversity of gender identities, all participants who were assigned male at birth are referred to as TGW.

In the qualitative phase, we used a purposive sampling approach to recruit 16 TGW with AAC from the PATCH study who were referred to HRA based on their HRA completion status (eight participants who did not complete HRA and eight who completed HRA).

After a study clinician discussed the result with the participant, a study team member scheduled an appointment at an off-site clinic in Washington, DC, that was chosen by the patient based on preference and proximity. Appointments were readily available and usually scheduled within 2–3 weeks of discussion of abnormal results. For participants who missed the scheduled visit, study staff would assist in rescheduling subsequent appointment(s). For both analyses, HRA referrals were defined as (1) communication of an abnormal result with the participant by the study clinician and (2) scheduling of HRA appointment by a study team member. HRA completion was defined as undergoing HRA within 3 months from the abnormal cytology result.

Ethics statement

The study protocols were approved by the University of Maryland, Baltimore’s IRB (protocol HP-00090161 and HP-00105487). All participants provided informed consent and were compensated for their time.

Data collection

Quantitative data collection

As part of the PATCH study, participants had anal cytology, blood samples, and interviewer-completed surveys on demographics, gender-affirming hormone (GAH) use, and sexual behavior collected at screening. HRA results were based on pathology reports shared by the off-site HRA clinics. HIV status was defined based on HIV fourth-generation antigen/antibody testing and medical history. HIV viremia was defined as an HIV viral load ≥200 copies/mL. Gender-affirming care was conceptualized as the self-report of GAH use.

HRA referral and facilitated linkage

Anal cytology results were evaluated by a study clinician who determined the appropriateness for HRA referral. In general, participants were referred to HRA if they had AAC, defined as high- or low-grade squamous intraepithelial cells, or atypical cells of either undetermined significance or without the ability to rule out high-grade changes. Because our data collection preceded the publication of the current guidelines for anal cancer screening, participants testing positive for HPV16 with normal cytology were not referred to HRA. ^4,5

Qualitative data collection

We used the findings from the quantitative phase to develop a semi-structured interview guide based on the HRA completion status of participants. The interview guide covered knowledge of anal cancer and screening procedures and experienced and anticipated psychosocial facilitators and barriers to completion of HRA. The interviews were conducted remotely and recorded using a Health Insurance Portability and Accountability Act (HIPAA)-compliant audiovisual platform. The interviews took approximately 45 min to complete. A third-party transcription service was used to transcribe interview audio.

Data analysis

Quantitative analysis

We compared participant characteristics by HRA completion status using the chi‐square or Fisher’s exact tests where appropriate. A p value of <0.05 was considered statistically significant. All analyses were conducted using SAS 9.4 (Cary, NC).

Qualitative analysis

In the qualitative phase, we used a constant comparative analysis method, reviewing responses from each participant interview to refine questions and analysis of emergent themes from participants. Following the completion of interviews, we used thematic analysis to analyze transcripts. Each transcript was coded by two members of the study team, using a priori codes developed from existing literature related to facilitators and barriers for HRA. In total, two rounds of coding were conducted using the tabletop method for code reduction. ¹³ The full study team then created themes from the second-level codes. Data analysis was conducted using Dedoose. ¹⁴ We used the weave approach for mixing the two phases of data collection and combining the results at the interpretation phase in which narratives were created through emergent themes. ¹⁵

Results

Baseline characteristics

Of 75 TGW who had anal cytology completed in PATCH, 36 (48%) had an abnormal result. Of those, 32 (89%) were referred to HRA, and 15 (42%) completed HRA (Fig. 1). In those who completed HRA, 2 (20%) had histological HSIL, 2 (13%) had low-grade squamous intraepithelial lesions, and 10 (67%) had a normal exam (Fig. 2). Of the 32 TGW with abnormal cytology who were referred to HRA, 32 (100%) were Black, 23 (72%) were 35 years old or older, 21 (66%) were unemployed, 20 (62%) did not have stable housing, and 19 (59%) reported current use of GAH (Table 1). Within the past year, 14 (44%) reported engaging in sex work, and 22 (69%) reported receptive anal sex. Further, 26 (81%) were LWH, and of those, 11 (42%) were viremic (Table 1).

FIG. 1.

Anal cancer screening cascade among 75 transgender women. HRA, high-resolution anoscopy.

FIG. 2.

Results of high-resolution anoscopy among 15 transgender women. HSIL, high-grade squamous intraepithelial lesions; LSIL, low-grade squamous intraepithelial lesions.

Table 1.

Baseline Characteristics of Transgender Women with Abnormal Anal Cytology who were Referred to High-Resolution Anoscopy (HRA)

Characteristic	Total n/N (%)	HRA completed n/N (%)	HRA not completed n/N (%)	p Value
Sociodemographics
Race
Black	32/32 (100)	14/32 (44)	17/32 (56)	NA
Non-Black	0 (0)	0 (0)	0 (0)
Age
<35 years	9/32 (28)	5/9 (56)	4/9 (44)	0.71
≥35 years	23/32 (72)	9/23 (39)	14/23 (61)
Employment
Unemployed	21/32 (66)	6/21 (29)	15/21 (71)	Ref
Employed	8/32 (25)	6/8 (75)	2/8 (25)	0.02
Other	3/32 (9)	2/3 (67)	1/3 (33)	0.19
Housing
Unstable housing	20/32 (62)	8/20 (40)	12/20 (60)	0.58
Stably housed	12/32 (38)	6/12 (50)	6/12 (50)
Sexual behavior
Sex work in the last year
Yes	14/32 (44)	5/14 (36)	9/14 (64)	0.65
No	18/32 (56)	9/18 (50)	9/18 (50)
Receptive anal sex in the last year
Yes	22/32 (69)	10/22 (46)	12/22 (54)	0.77
No	10/32 (31)	4/10 (40)	6/10 (60)
Number of sex partners in the last year
One or less	15/32 (47)	8/15 (53)	7/15 (47)	0.33
Two or more	17/32 (53)	6/15 (35)	11/15 (65)
HIV-associated factors
HIV status
Living with HIV	26/32 (81)	12/26 (46)	14/26 (54)	0.57
Not living with HIV	6/32 (19)	2/6 (33)	4/6 (67)
Seeing a provider for HIV care in the last year *
Yes	23/26 (88)	11/23 (48)	12/23 (52)	0.22
No	3/26 (12)	1/3 (33)	2/3 (67)
HIV viral load *
<200 copies/mL	15/26 (58)	10/15 (67)	5/15 (33)	0.01
≥200 copies/mL	11/26 (42)	2/11 (18)	9/11 (82)
HPV-associated factors
High-risk HPV status
Positive	29/32 (91)	13/29 (45)	16/29 (55)	0.7
Negative	3/32 (9)	1/3 (33)	2/3 (67)
Ever received HPV vaccine
Yes	7/32 (22)	3/7 (43)	4/7 (57)	Ref
No	21/32 (66)	9/21 (43)	12/21 (57)	1
Unknown	4/32 (12)	2/4 (50)	2/4 (50)	0.82
Ever had an anal pap
Yes	16/32 (50)	8/16 (50)	8/16 (50)	Ref
No	13/32 (41)	5/13 (38)	8/13 (62)	0.53
Unknown	3/32 (9)	1/3 (33)	2/3 (67)	0.6
Gender-affirming hormones
Current use of gender-affirming hormones
Yes	19/32 (59)	5/19 (26)	14/19 (74)	0.46
No	13/32 (41)	2/13 (15)	11/13 (85)
Location of getting hormones **
Clinic	18/19 (95)	8/18 (44)	10/18 (56)	NA
Street	1/19 (5)	1/1 (100)	0/1 (0)

^*Among those who are living with HIV.

^**Among those currently on hormones.

HPV, human papilloma virus.

The qualitative sample included 16 participants from PATCH, of whom 16 (100%) were Black, 13 (81%) were 35 years old or older, 3 (19%) had unstable housing (both at the time of interview and of enrollment in the PATCH study), 11 (69%) reported receptive anal sex within the last year, and 15 (94%) were LWH (Table 2).

Table 2.

Characteristics of Transgender Women with Abnormal Anal Cytology who were Interviewed

Characteristic	Total n/N (%)	HRA completed n/N (%)	HRA not completed n/N (%)
Sociodemographics
Race
Black	16/16 (100)	8/16 (50)	8/16 (50)
Non-Black	0 (0)	0	0
Age
<35 years	3/16 (19)	3 /3 (100)	0 (0)
≥35 years	13/16 (81)	5/13 (38)	8/13 (62)
Housing
Unstable housing	3/16 (19)	0 (0)	3/3 (100)
Stably housed	13/16 (81)	8/13 (62)	5/13 (38)
Receptive anal sex in the last year
Yes	11/16 (69)	6/11 (55)	5/11 (45)
No	5/16 (31)	2/5 (40)	3/5 (60)
HIV status
Living with HIV	15/16 (94)	7/15 (47)	8/15 (53)
Not living with HIV	1/16 (6)	1/1 (100)	0 (0)

HRA, high-resolution anoscopy.

Socioeconomic factors

Of 32 participants referred to HRA, those who were employed were significantly more likely to complete HRA compared with those who were unemployed (75% vs. 25%; p = 0.02) (Table 1). A participant in the qualitative phase described how a lack of employment was linked to her not completing HRA: “And I had to pay for it myself, because I don’t have a job or nothing” (TGW who did not complete HRA).

When taking housing status into consideration, rates of HRA completion were comparable when looking at those with stable (50%) and unstable housing (40%; p = 0.58) (Table 1). However, participants in the qualitative phase described the importance of housing and transportation in the completion of HRA. For example, one participant suggested that available transportation would make it easier to complete her appointment “It would be good if I can get a lift of the appointment. That would make it easier” (TGW who did not complete HRA). One participant mentioned lack of stable housing as a potential barrier to TGW not comp leting HRA: “If you’re homeless you don’t know the sources to go to” (TGW who completed HRA).

HIV-associated factors

In the quantitative phase, participants with HIV viremia had 3.7 times lower odds of completing HRA compared with those without HIV viremia. Among those LWH, 10/15 (67%) with a suppressed HIV VL completed HRA, compared with only 2/11 (18%) of those with HIV viremia (p = 0.01). Of note, the proportion of participants with HIV who saw a provider within the last year was comparable based on HRA completion status (92% in those who completed HRA and 86% in those who did not complete HRA; p = 0.22) (Table 1). HIV control was not mentioned as a factor affecting HRA completion in the qualitative phase.

Gender-affirming care

In the quantitative phase, use of GAH was not associated with HRA completion (26% in those who were using GAH versus 15% in those who were not using GAH; p = 0.46). However, in the qualitative phase, getting care that was affirming of the participants’ gender identity was identified as a facilitator to completing HRA: “-Was there anything specific about the clinic that made it easier for you to do the procedure? (Interviewer)—Yes, because the clinic I went to treated you with respect.” (TGW who completed HRA). Meanwhile, transphobic experiences of care including misgendering were considered a barrier to completing HRA: “I was in a doctor’s waiting room waiting for her to come for a whole hour. I had to step outside the door and ask the nurse where the doctor was at. And then when she sees me, she going to say “Oh, he needs the doctor” […] So that was a disrespect and totally a turnoff. So that’s one of my reasons why I have not been back there for real.” (TGW who did not complete HRA).

Influence of sexual practices

In the quantitative phase, we did not find any statistically significant differences in the completion of HRA between participants based on sexual behavior. Rates of HRA completion were not significantly different based on engaging in transactional sex (50% of those who did not engage vs. 36% of those who engaged; p = 0.65) or on engaging in receptive anal sex (40% of those who did not engage vs. 46% of those who engaged; p = 0.77). However, in the qualitative phase, participants who completed HRA and those who did not complete HRA considered the ability to sustain engagement in sex work as a motivator for completion of HRA. Notably, this motivation was linked to socioeconomic factors and sustainability of income. One participant said: “Because I needed to know if I was at risk of anything else that I needed be more careful on because it was at one point in time where I was doing street work.” (TGW who completed HRA). Another participant described: “Me personally, in my experiences, I just know, wanting to know what’s going on with me health-wise, especially because I’m a sex worker and just knowing that that’s one of my options of making money and needing to know what’s going on with that.” (TGW who did not complete HRA).

Discussion

Our study sought to examine the rates of and factors associated with completion of HRA among TGW. In a cohort of TGW with high rates of AAC, completion of HRA was low, highlighting missed opportunities in anal cancer prevention among TGW. Our data reflect real-life challenges associated with the anal cancer screening cascade and the completion of HRA. Although the primary hurdle to the implementation of HRA, both in the US and internationally, is thought to be the dearth of providers proficient in HRA, ⁸ we found that even in an urban setting where HRA appointments are readily available within a couple weeks, completion of HRA was suboptimal. Populations at highest risk for anal cancer are also the populations who are facing the most barriers to accessing HRA: in our case Black TGW of low socioeconomic status (SES) with high rates of AAC, HIV, and HPV infection. Evidence-based interventions and implementation strategies are needed in such groups to ensure referral to HRA, completion of HRA, and potentially longitudinal engagement in HRA for HSIL treatment and cancer prevention.

In our cohort of TGW, low SES was associated with limited HRA completion. Particularly, despite having health insurance, participants considered financial concerns (unemployment and lack of stable housing or reliable transportation) as barriers to completing HRA. This data supports findings from national registries of 9550 cases of anal cancer, where low household income independently predicted lower cancer-free survival rates and higher cancer mortality. ¹⁶ In addition, a study of 155 MSM with HSIL from a federally qualified health center found that the use of HIV or Pre-exposure prophylaxis (PrEP) case management services, considered by those authors as a proxy to low socioeconomic status, was associated with decreased longitudinal engagement in HRA for HSIL treatment. ¹⁷ Anal cancer screening in TGW at risk should include a holistic approach acknowledging socioeconomic challenges that TGW may face and how these factors can become barriers to completing HRA. Health care providers and systems should integrate assistance with transportation for TGW needing socioeconomic support to improve anal cancer screening. Additional research is needed to develop programs which address socioeconomic factors that hamper HRA completion. Of note, despite the underrepresentation of unhoused TGW in our qualitative phase, housing status was still considered a major barrier to HRA completion. This reflects that lack of stable housing is an even bigger barrier to HRA completion than measured in our data and further studies on anal cancer screening among TGW who lack stable housing are needed.

Our results show lower rates of completion of HRA among TGW with HIV viremia compared with those with controlled HIV infection. This association likely indicates that factors leading to HIV viremia, such as low SES and experience of health care stigma, ¹⁸ may also serve as barriers to HRA linkage. This finding is of particular concern because TGW with HIV viremia are at higher risk of developing HSIL and progressing from HSIL to cancer due to uncontrolled HIV infection. ^5,19 While the Centers for Disease Control and Prevention provides a list of evidence-based interventions focusing on linkage and retention of TGW with HIV in care, no such interventions have been developed for HRA linkage. ²⁰ Therefore, in addition to ensuring adherence to antiretroviral therapy in TGW, such interventions should be evaluated for the ability to concurrently improve anal cancer screening in TGW LWH. This is of particular importance in people LWH, since the ANCHOR trial examined the benefit of treating anal dysplasia specifically in this population. ⁶

In our cohort of TGW, trans-affirming care was identified as a facilitator to completing HRA, indicating the importance of a welcoming environment to transgender patients as part of HRA programs. Our participants generally had access to health care with 95% of TGW taking GAH getting those GAH from a clinic, and 9 out of 10 TGW LWH reporting a provider visit for HIV care within the year prior to enrollment. These findings align with conclusions from a qualitative study of people LWH who reported that trust in health care providers encouraged patients to complete anal cancer screening. ¹¹ Responses from the qualitative assessments highlighted that the quality of care regarding gender identity was a major factor in HRA completion. As many existing HRA programs may have a more targeted focus on MSM, building a gender-affirming environment for TGW among both referring providers (who screen patients with anal swabs), and those who are performing HRA is critical in improving retention in the anal cancer screening cascade in TGW. Transgender peer HRA educators may play an important role in creating such an environment. Further, as the HRA capacity and workforce expands, programs educating new providers on HRA practice should include trans-affirming care as a compulsory element.

While sexual behaviors were not significantly associated with HRA linkage, engaging in anal sex and sex work were recognized as motivators to completing HRA among TGW. This finding is consistent with focus groups of MSM LWH in Atlanta which found that linking anal cancer screening to the maintenance of healthy receptive anal sex would increase engagement in cancer screening among those at risk. ²¹ As such, public health interventions targeting TGW who engage in sex work and/or receptive anal sex should highlight the importance of anal cancer screening in preserving such sexual practices.

Of note, although anal cytology and/or HPV testing are the only tests recommended by guidelines for initial screening, more specific methods are needed to improve triaging to HRA. In our data, 67% of TGW with abnormal cytology had normal HRA exams. Screening tests that are more specific may allow us to better focus our efforts on linkage to HRA. As new diagnostics are developed, the inclusion of TGW in investigational studies is essential to ensure the generalizability of these tests to this population. ²²

Our study has some limitations. Our limited sample size and convenience sampling restrict the generalizability of our findings. Our cohort primarily included Black TGW living in an urban setting, a population underrepresented in anal cancer research, recruited through a community-academic collaboration. Our quantitative tools did not assess knowledge, attitudes, or behaviors toward HPV or anal cancer screening, which limits our mixed-methods approach in discussing findings pertinent to these topics.

In a population of TGW with AAC in Washington, DC, we found low rates of completion of HRA. Interventions aiming to improve the anal cancer screening cascade in this population should address socioeconomic barriers that TGW face. Anal cancer screening programs should prioritize trans-affirming care and highlight the maintenance of healthy anal sex practices as motivators to facilitate HRA completion among TGW. In addition, a concurrent focus on adherence to antiretroviral therapy in TGW LWH with HIV viremia is important to reduce the risk for anal cancer. Overall, targeted efforts to improve the anal cancer screening cascade should focus on the specific needs of this population and are critical to reduce anal cancer among TGW.

Authors’ Contributions

All authors have reviewed the article and provided edits. O.H., D.W., T.M., C.V., and M.M. collected and analyzed qualitative data. R.E., E.E., A.D., M.Z., A.C., P.B., R.S., D.S., T.L., G.G., M.J., and R.K. collected quantitative data. O.H. and H.O. analyzed quantitative data.

Author Disclosure Statement

S.K. reports grants and other support from the CDA Foundation, Gilead Sciences, Orsobio, and Red Queen Therapeutics. E.S.R. reports grants and nonfinancial support from Gilead Sciences and Merck.

Funding Information

We acknowledge the support of the University of Maryland, Baltimore, the Institute for Clinical & Translational Research (ICTR), and the National Center for Advancing Translational Sciences (NCATS) Clinical Translational Science Award (CTSA). This work was supported in part by the Office of AIDS Research (grant HHSN272201300022I; PI E.S.R.). This work was also supported by the National Center for Advancing Translational Sciences (grant UL1-5UL1TR003098).