Integrating HPV Vaccination Within PrEP care Delivery for Underserved Populations: A Mixed Methods Feasibility Study

Abstract

Human Papillomavirus (HPV) vaccination is effective at preventing anal cancer, which disproportionally impacts gay/bisexual men (GBM) and transgender women (TGW). Vaccine coverage among GBM/TGW is insufficient to reduce anal cancer disparities. Federally qualified health centers (FQHCs) can increase reach and uptake of HPV vaccination by integrating and promoting HPV vaccination in ongoing HIV preventive care (e.g., Pre-exposure Prophylaxis [PrEP]). The purpose of the current study was to assess the feasibility and potential impact of integrating HPV vaccination with PrEP care. We conducted a mixed methods study of PrEP providers and staff (qualitative interviews, N = 9) and PrEP patients (quantitative survey, N = 88) at an FQHC in Philadelphia, Pennsylvania. Qualitative thematic analysis of PrEP provider/staff interviews was informed by the Exploration, Preparation, Implementation, Sustainment (EPIS) framework to identify and describe barriers and facilitators to HPV vaccination implementation. Quantitative analysis of PrEP patient survey was informed by the Information-Motivation-Behavioral Skills Model. Quantitative interviews resulted in 16 themes related to characteristics of the inner and outer clinic context. Barriers among providers included lack of focus on HPV in PrEP management guidelines, in metrics mandated by funding agencies, and in electronic medical record templates. Lack of anal cancer specific knowledge and motivation was identified in both PrEP patients and providers/staff. Providing HPV vaccination during routine PrEP visits was highly acceptable to both patients and providers. Based on these findings, we recommend several multi-level strategies to increase HPV vaccine uptake among PrEP patients.

Introduction

Anal cancer disproportionally impacts gay, bisexual, and other men who have sex with men (GBM), in addition to transgender women (TGW) [1-4]. These populations experience a syndemic of anal cancer risk factors that include prevalent oncogenic anal human papillomavirus (HPV) infections, concurrent sexually transmitted infections (STIs), and related behavioral factors (e.g., unprotected anal intercourse) [1, 2, 4]. Anal cancer incidence among GBM ranges from 37 to 131 cases per 100,000 [1, 2, 5, 6], roughly 20 to 80 times higher than anal cancer rates in the general population. While incidence data for TGW is unavailable, evidence suggests that TGW are at high risk for precancerous anal lesions, indicating elevated risk for anal cancer similar to or greater than GBM [3].

The 9-valent HPV vaccine is indicated for the prevention of anal cancer [7]. Currently, HPV vaccination is recommended for adolescents aged 11 and 12. After that, catch-up HPV vaccination is recommended for all adults through age 26, and shared clinical decision-making is recommended for adults 27 to 45 [8]. Coverage among adolescent males in the general population is currently insufficient (~ 52%) to reduce anal cancer disparities. Most recent estimates indicate that HPV vaccine initiation was just 33% among GBM aged 18–26 and 13% among those aged 27 and older [9]. There are also large cohorts of GBM for whom HPV vaccination would be indicated who were either not eligible because of their age (i.e., older than 26) or who aged out of the original recommendations. There are also ethnoracial disparities in vaccine uptake which is lower among Black and Hispanic GBM [10]. Vaccination rates for TGW are largely unknown due to limited research [9, 11].

Key barriers to anal cancer prevention in these populations is lack of awareness and misperceptions of anal cancer risk and the utility of HPV to reduce that risk [12, 13]. For example, there is a widespread misperception among GBM that HPV is entirely a women’s health issue, and that HPV vaccination is only for cervical cancer prevention [14-16]. Knowledge regarding anal cancer risk (e.g., infection with HPV) and prevention (e.g., HPV vaccination) is low among GBM [15, 17-20] and TGW (e.g., HPV can cause anal cancer) [11].

Uptake and completion of HPV vaccination in GBM/ TGW populations are further constrained by healthcare related factors [21, 22]. Systematic reviews have shown that GBM/TGW populations have moderate to high acceptability of HPV vaccination when educated about the protective effects of HPV against anal cancer. However, there are widespread missed opportunities for HPV vaccination among GBM/TGW engaged in primary care [23, 24]. Increasing access and convenience were key factors related to HPV vaccine decisions [16, 25]. Thus, promoting HPV vaccination among GBM/TGW who are already accessing HIV prevention services (e.g., Pre-exposure prophylaxis [PrEP]) has the potential to increase reach and equity [26]. Previous research has demonstrated that PrEP patient populations are underutilizing HPV vaccination despite frequent contacts with healthcare providers [10, 27, 28].

There is an existing infrastructure for HIV prevention and outreach specifically for GBM/TGW that includes PrEP management. Nationally, 79.2% of GBM are engaged in yearly HIV testing and 35.1% report using PrEP [29]. The 3-dose HPV vaccine series for adults coincides with PrEP management recommendations and the frequency of HIV testing; however, most GBM/TGW on PrEP have not initiated HPV vaccination. In a community-based survey of GBM/TGW, just 43.8% of vaccine eligible active PrEP users had initiated HPV vaccination [28]. In a separate survey of vaccine-eligible Black and Hispanic GBM and gender diverse participants, just 46.5% had initiated HPV vaccination and PrEP use was not associated with HPV vaccine uptake [10]. In that study most participants were undecided (56.3%) about initiating HPV vaccination in the next 12 months. In a separate analysis of an urban midwestern clinic, just 21.8% of PrEP patients were vaccinated [27].

To capitalize on the opportunity to integrate HPV vaccination protocols within existing PrEP management infrastructure, research is needed to identify multi-level barriers to the implementation of HPV vaccination in clinics providing PrEP care to GBM/TGW. A focus on federally qualified health centers (FQHCs) is a logical and pragmatic first step to examining such barriers given that many GBM/TGW selectively seek sexual health services at community health centers perceived to be safe places for lesbian, gay, bisexual, and transgender (LGBT) populations [30]. In fact, because of shifts in the healthcare landscape, LGBT community health centers have increasingly been recognized as FQHCs and operate in most major cities in the U.S. [31]. Therefore, we assert that FQHCs can increase reach and uptake of HPV vaccination by integrating and promoting HPV vaccination in HIV preventive care received by GBM/TGW. Thus, our purpose was to assess the feasibility and potential impact of integrating HPV vaccination with PrEP care.

Methods

We conducted a parallel mixed methods case study of PrEP stakeholders at an FQHC providing comprehensive healthcare services in a large urban area with a high poverty rate. Data were collected in 2021 and 2022. Stakeholders were medical providers and staff members engaged in providing PrEP care, as well as the patients who were engaged in PrEP care at that FQHC within the previous two years. Research methods were informed by two theoretical approaches. First, the Exploration, Preparation, Implementation, Sustainment (EPIS) framework was used to identify and describe theoretically relevant barriers and facilitators to HPV vaccination implementation [32]. Second, the Information-Motivation-Behavioral Skills Model (IMB) was used to understand individual level patient factors related to HPV vaccine decision making [33]. Data collection took place in 2021 and 2022. All study protocols were approved by the institutional review board of the first author as well as the FQHC’s own IRB.

Recruitment and Procedures

PrEP patients.

We actively recruited patients who were (1) between the ages of 18 to 45, (2) spoke and read English, (3) were patients at the FQHC with at least 1 PrEP related healthcare visit within the previous two years, and (4) who identified as gay, bisexual, queer, and/or transgender. Eligible participants were identified through a query of the electronic medical records, which contains sexual orientation and gender identity. Those who meet eligibility requirements were contacted a maximum of three times through email or phone. If a patient was interested in participating, a research assistant confirmed their identity with a phone screening interview. Informed consent was completed over the phone (a waiver of documented consent was approved) and a unique link to an online Qualtrics questionnaire was sent to each participant. Participants received a $20 gift card as an incentive. A total of 289 patients met inclusion criteria and were contacted. Of the 289, 114 agreed to participate and were emailed or texted individual survey links. Of those, 88 completed the study (30.8% response rate).

PrEP providers.

All prescribing physicians, nurses, and staff members engaged in the PrEP program were invited to participate in the qualitative interviews. A research assistant contacted each staff member via email to provide information about the study and obtain written documented informed consent. Individual interviews (30 to 45 min on average) were conducted remotely over Zoom. Interviews were recorded and transcribed verbatim. An honorarium was provided to the FQHC to cover provider/staff time. Of the 12 staff members meeting inclusion criteria, 9 agreed to participate and completed an interview (75% response rate).

Measures

Survey of PrEP Patients

Measures were derived from previous research and the IMB model [33]. Following a brief introduction about HPV vaccination, participants were asked: “To the best of your knowledge, have you ever gotten the HPV vaccine shot? Even if just 1 of the 3 shots?” Response options were Yes, No and Not sure. Three items measured HPV vaccine intention among those who were unvaccinated. The first item assessed intention to initiate HPV vaccination (i.e., “get the first shot”) within the next 12 months. Responses were recorded on a 5-point Likert-type scale (definitely will, probably will, unsure, probably will not, definitely will not). To determine acceptability of initiating vaccination during PrEP follow-up visits, the second item asked, “How likely is it that you would agree to get the HPV vaccine if it was offered to you the next time you had an appointment to get PrEP?” A similar item asked about getting vaccinated “next time you were tested for HIV.” Responses were recorded on a 5-point Likert-type scale (very likely, likely, neither likely nor unlikely, unlikely, very unlikely).

HPV and anal cancer knowledge was assessed with an 11-item measure combining items from previous research focused on risk, prevention, and consequences [15, 34, 35]. Responses were categorical (yes, no, not sure) and summed to form the HPV Knowledge (Cronbach α=0.77) and Anal Cancer Indices (Cronbach α=0.79). Perceived information was measured with one item (“I need more information about the HPV vaccine before I decide whether or not to get vaccinated”) with responses measured on a 5-point Likert-type scale. Participants were then asked to choose from a list all of the topics they wanted to know more about before making their decision. This included risk for anal cancer, safety of HPV vaccination, how well HPV vaccination works, why HPV vaccination is beneficial, and other ways to prevent anal cancer.

Two items were used to measure perceived benefit of HPV vaccination that focused on “how effective” HPV vaccination is in “preventing you from getting anal cancer” and how likely it is that “you will benefit from HPV vaccination.” Reponses were recorded on 5-point Likert-type scales and averaged into a single score (α=0.62). Behavioral skill was assessed by 3 items measuring self-efficacy in “asking a doctor about anal cancer,” feeling confident that one’s doctor “…is knowledge about anal cancer,” and feeling “comfortable talking to a doctor about anal cancer.” Reponses were recorded on 5-point Likert scales and averaged into a single score (α=0.78). Sociodemographic characteristics and healthcare related variables were measured. Age categories were created to examine differences in between the catchup age (aged 18–26) and the shared clinical decision making (aged 27–45) recommendations.

Semi-structured interview guide

A semi-structured interview guide was constructed based on the main constructs from the EPIS framework [32]. Open-ended questions focused on eliciting description of the inner (e.g., characteristic of the clinic, PrEP providers and related staff, patient-provider discussions about HPV/anal cancer) and outer contexts (e.g., patient characteristics, inter-organizational environment, and service environment). Example questions include: “In what ways are you involved with providing PrEP care?” “In what ways are you currently involved with providing HPV vaccination?” “What overlap currently exists with providing PrEP and HPV vaccination?”). Probes were used to get more detail, clarify responses, and get specific examples. The questions were developed and reviewed by a multidisciplinary team with expertise in HPV, PrEP, health services, and qualitative methods.

Analysis

Qualitative Analysis

Qualitative thematic analysis was conducted on transcribed text using Dedoose Version 9.0.17 (SocioCultural Research Consultants, Los Angeles, CA). A five-step process was used to analyze the qualitative data [36]. First, transcripts were coded using constructs from the EPIS. In vivo coding was then used to identify text within the main categories that exemplify that category. These codes were combined into generic categories and then interpreted into conceptually meaningful themes. Themes were checked for trustworthiness through peer debriefing, reflexively reviewing the themes against the memos written after the interviews, triangulating findings with the patient survey results, and participant validation (i.e., member checking) [37, 38].

Quantitative Analysis

All analyses were conducted in SAS 9.2 (SAS Institute, Cary, NC). Descriptive statistics were calculated for all variables. Chi-square test of independence or Fisher’s exact test were used to examine bivariate differences between sociodemographics, HPV/anal cancer knowledge, and vaccine status (≥ 1 dose of HPV vaccination vs. 0 doses). The analytic sample was then restricted to participants who had not initiated HPV vaccination (n = 59). Differences in awareness and informational needs between the vaccine age cohorts (18–26 vs. 27–45) were explored. Crude prevalence ratios were estimated with acceptability of receiving HPV vaccination at next PrEP visit as the outcome. Acceptability was dichotomized to compare very high acceptability (i.e., very likely) with all other responses.

Results

Characteristics of the Study Samples

The clinic was a FQHC providing comprehensive healthcare services in a large urban area with a high poverty rate. Nine stakeholder interviews (3 PrEP prescribing physicians, 3 nurse practitioners/nurses, 3 PrEP patient navigators) and 88 PrEP patient questionnaires were completed. Results are reported based on the EPIS constructs.

Inner Context

Organizational Characteristics

Five main themes emerged pertaining to the organization’s characteristics (Table 1). The adolescent clinic was more focused on checking vaccine histories, especially regarding HPV vaccination, compared to adult clinics (theme 1). This was driven in part by the perception of urgency for adolescents and by quality metrics (see results for service environment). Follow-up appointments with patients taking PrEP were also described as “niche” (theme 2). These appointments were guided by internal templates in the electronic medical record (EMR) that focused on STI screening, HIV exposures, and PrEP adherence. These templates did not include questions about HPV vaccination. But modifying these templates was described as easy as the organizational culture was highly amenable to changes that could improve HPV vaccination rates (theme 3). There were also two other facilitators of HPV vaccination described. The EMR connected to local vaccine registries where HPV vaccination is reportable (theme 4). There were also organizational events (e.g., clinic case conferences and special events) that could be used to deliver patient and provider education on HPV and HPV vaccination (theme 5).

Table 1.

Theoretical constructs connected to the qualitative themes with sample quotes (N = 9)

EPIS Construct	Themes	Sample quotes
Inner Context
Organizational Characteristics	Theme 1: Adolescent clinic is more focused on vaccinations	Maybe it’s either assumed [the adult patient] had all their vaccines or it’s not as urgent. I know that they check about the flu vaccine for sure. And like, shingles, pneumonia, like all of those…are like very much measures they’re trying to reach, but I really don’t ever hear anything about the HPV vaccine. (Nursing staff)
	Theme 2: EMR template structures interactions with PrEP patients that currently do not focus on HPV vaccination	I actually think that the PrEP visits are sort of put in this niche where you just focus on STI screening, and are you taking your prep, and it sort of ends there. It [HPV vaccination] is not on the template. (Prescribing physician)
	Theme 3: Organization culture is amenable to changes that can improve HPV vaccination	I would say that we are pretty flexible. And a lot of the clinicians and other staff are really open to new ideas, open to doing things differently. And yeah, just like really collaborate and work together well. And just center the patient in everything that we do. (PrEP outreach/retention coordinator) There is one person in our practice, who sort of modifies templates…we would just sort of probably talk about it as a provider group and say, ‘Hey, guys, let’s do this [add HPV vaccination to PrEP template.’ It would be really easy. (Prescribing physician)
	Theme 4: EMR interfaces with local vaccine registries that include HPV but does not current prompt providers	EMR just has a list of their current vaccines…And then it’s kind of up to the provider to know if they’re due for something for adults. (Prescribing physician)
	Theme 5: Existing organizational events can be leveraged to educate patients and providers about HPV vaccination	We have a weekly case conference for all the providers, and…the administrative folks. If something was like, a major change like that [HPV vaccine recommendation], there will be a whole case conference dedicated to that topic. That hasn’t happened with the HPV vaccine. (Prescribing physician) In the past… we’ve had, pap-a-thons. And during those pap-a-thons, we have had patients that do not have the cervix get scheduled by accident. And with those patients, we’ve done an anal pap on them. …If we make it like this thing, like, we’re doing all our anal paps this month, and I don’t think a lot of people even know that it’s something that should be a part of their sexual health care. (Nursing staff) I know that there’s was the [anal health] summit that was happening before COVID. And it [anal cancer] was on a lot of people’s radar for that. (Nursing staff)
Provider/Staff Characteristics	Theme 6: Motivation was high among providers and PrEP staff but more information was needed	I feel pretty passionately about trying to get everybody vaccinated against HPV” (Prescribing physician) I feel like I know very little about it. I know that I have been vaccinated against HPV and that it’s something that we will definitely like, coordinate for patients. It feels like it’s kind of not in my lane and I don’t really know a lot about any intersections between HPV and HIV (PrEP outreach/retention coordinator) I don’t understand the change [change in age recommendation] fully. I’ll be honest with you. (Prescribing physician) I will admit, I don’t talk as much or as much as I should about potential oral cancers… I’m less familiar with it [oral cancer]. (Prescribing physician)
	Theme 7: Uncertainty around shared clinical decision-making recommendation for 27–45 year olds	I don’t offer it to a lot of my patients who would be in that age group who are on PrEP. Just because their exposure history, they’ve probably been sexually active since a pretty young age. that point, you know, the benefits may not be so great. So I personally have not offered it. I don’t think I’ve offered it to anybody in that age range, for that reason, but also because of insurance coverage. And I don’t know, you know, I just don’t know, which insurance companies are actually paying for it now. (Prescribing physician)
Patient-Provider Discussions	Theme 8: Anal cancer is more connected to patient-provider discussions about anal pap testing then HPV vaccination—particularly among patients with HIV (i.e., not PrEP patients).	There is so much information that I’m giving them [PreP patients]. I’m a bit worried about overloading them with information…But it’s definitely needed. I think we could put it in the [PrEP] template. (PrEP outreach/retention coordinator) it comes up. Not, but not totally, very often. I always I make it a point to offer annual cancer screening for my HIV positive gay men. But less of a point to do that, in my HIV negative population, whether even if they’re on prep or not. (Prescribing physician) I would say the times it’s come up have been more with my HIV positive patients. (Nursing staff) If it’s an HIV positive person it’s a little bit more likely that they may have heard about anal cancer just because they may know somebody who’s gone through even if it’s not cancer, just screening for anal disease…particularly depending on how long they’ve been HIV infected. If it’s a new HIV infected person, then no they won’t. They don’t know anything about it. (Prescribing physician)
Staffing	Theme 9: PrEP coordinators were central to community outreach and providing sexual health information	Every patient who is getting PrEP has seen and knows a PrEP coordinator. The PrEP outreach coordinator does community outreach so those folks meet one-on-one with PrEP patients to really focus on adherence and help them liaise with the clinic and their providers. (Prescribing physician) Every three months we [the PrEP coordinator] do a sexual risk assessment…And we always talk about STDs every three months…HPV rarely comes up. I will, I will say it in the beginning, if you’re not using condoms, like these are the things that can happen, you know, and especially if a patient says, oh, all the other stuff is curable. I’m like, curable or treatable. There’s a difference. And so then HPV and herpes does come up. (PrEP outreach/retention coordinator)
	Theme 10: HPV vaccination was not a part of routine sexual health information provided by PrEP coordinators	I think it [HPV vaccination] really doesn’t come up that often. When I’m checking patients’ charts, I do check to see if they’ve been…because we have the patients right before they hit the cut off. So we see them up until 25. So I checked the charts to see if they had been vaccinated. If they haven’t, then I would put it and make a note to the provider and the provider would schedule it with the lab to for that to happen. (PrEP outreach/retention coordinator) We really don’t get a lot of time with patients and want to dive into these pieces that are specific to HIV, just because that’s our lane. If people do bring up any concern about HPV or questions, that would be something I typically say, hey, let me like, shoot your doctor a message. (PrEP outreach/retention coordinator)
Outer Context
Patient Characteristics	Theme 11: PrEP patients at FQHCs are diverse and have a variety of needs	It can be somebody who is sort of like a higher functioning, working professional 20s 30s. You know white, Hispanic, black males. I just happened to see three PrEP patients this afternoon. One was a white man from France. One was a black man from Philly, and one was a Latino man from Philly. All working professionals in their 30s. (Prescribing physican) It depends on the patient. I had a few patients who would come in with a notebook and they will have documentation that’s like every encounter with the questions they’ve asked their provider. If they’ve taken PrEP that day. Other patients that I’ve had.they understand why they’re taking PrEP, but it’s not on the top of their priority list. Because they have other barriers in their lives. So they are homeless, they need to find housing or they need to figure out how they’re going to eat and things like that. (PrEP outreach/retention coordinator)
	Theme 12: Lack awareness of HPV and anal cancer	I don’t think they’re even thinking about HPV at all. If you want me to be completely honest, you know, with PrEP…and I’m so I’m glad that my patients are coming in for PrEP. But I do feel that some of my patients are not thinking of the other STI ‘s that are out there. (PrEP outreach/retention coordinator) For PrEP patients the vast majority don’t bring it [anal cancer] up, they will only respond when I bring it up. (Prescribing physician)
	Theme 13: PrEP care may be fragmented from primary care	Probably 20 to 25% of my patients use us as a specialty clinic [for PrEP]. We’re an FQHC so we’re really supposed to be doing primary care. And we don’t bill as specialists. We bill as a primary care provider. But that doesn’t stop folks from coming to us for more specialty care. (Prescribing physician) I think there’s two main reasons. One is they’re not sure that their provider is knowledgeable and or interested in providing PrEP. Or they want to keep it separate, because they don’t want their provider to know that they’re taking PrEP, either because they don’t know of their sexual preference, or, you know, maybe some other reason. (Prescribing physician)
Inter-Organizational Environment	Theme 14: PrEP providers and patient navigators used a variety of outside resources for information about HPV and anal cancer	The American college of obstetricians and gynecologists. (Nursing staff) When I want to look into something like that, I look at the CDC guidelines, and I look at UpTo-Date. Those are the two main sources that I have. (Prescribing physician) I guess, just like CDC, or like the vaccine.org (Prescribing physician)
Service Environment	Theme 15: Funders for FQHCs set priorities with metrics that have not focused on HPV	Robust metrics that they need to meet in order to keep their funding and so they have a whole system in place to make sure that providers are offering all of the recommended sort of preventive care. (Prescribing physician) I usually focus on the vaccines that we would get dinged on as an FQHC. So those vaccines would be the influenza vaccine…recently, I think it’s hepatitis A, has become a new city-wide recommendation. And I don’t know if that’s a HRSA requirement or an AACO or Philadelphia Health Department requirement that we make sure that everybody’s HEP-A vaccinated and that gets followed up on, but there’s nothing like that on the HPV vaccine. (Prescribing physician) I know that they check about the flu vaccine for sure. And like, shingles, pneumonia, like all of those are like very much like measures they’re trying to reach, but I really don’t ever hear anything about the HPV vaccine. (Nursing staff)
	Theme 16: County-level vaccine registries can help facilitate HPV vaccination	There is a new there’s the Philadelphia vaccine registry, which our EMR does interface with. And that’s kind of a recent thing. So we can automatically import vaccine histories. (Prescribing physician)

Provider/staff Characteristics

PrEP providers and clinic staff were highly motivated to promote HPV vaccination, but they needed more information about HPV sequelae in men (i.e., anal and oral cancers), the intersection of HPV and HIV, and the age-based recommendations (theme 6). There was uncertainty about how to implement the most recent shared clinical decision-making recommendation for adults 27 to 45 (theme 7). Uncertainty was related to issues of efficacy for highly sexually active patients and insurance coverage for the mid-adult population.

Staffing

PrEP Outreach/Retention Coordinators were central in the clinical care of PrEP patients. They engaged in community outreach and provided sexual health education to PrEP patients (theme 9). However, HPV vaccination was not routinely discussed with PrEP patients during their consultations with the PrEP outreach/retention coordinators (theme 10). Some coordinators checked patients charts specifically for HPV vaccination (particularly for those in the catchup age range), but others believed HPV vaccination was outside the scope of their HIV prevention activities.

Outer Context

Patient Characteristics: Stakeholder Perspectives

There were three themes describing important characteristics of PrEP patients. The PrEP patients were diverse and had a variety of psychosocial needs (theme 11). This reflects the patient populations served by this FQHC, which include adolescents and adults who experience homelessness and food insecurity. Overall, PrEP patients were perceived as lacking basic information about HPV and anal cancer (theme 12). In some cases, PrEP patients intentionally sought PrEP care separate from their existing primary care (theme 13). In these cases, the FQHC was used as a specialty clinic where they received sexual health services in a non-judgemental and trusted environment.

Patient Characteristics: PrEP Patient Survey (Quantitative Results)

The survey of PrEP patients partially confirmed these findings. The sample was primarily cisgender gay-identified men, ethnoracially diverse, and had a variety of health insurance types. Approximately 60.2% of participants described the FQHC as their medical home (Table 2). Among those surveyed, 33.0% of PrEP patients had initiated HPV vaccination, but this varied by age. Those aged 18 to 26 were more likely to have initiated HPV vaccination compared to those 27 to 45 (50.0% vs. 25.0%, p = 0.02). Contrary to the perception of stakeholders, PrEP patients had basic knowledge about HPV. Knowledge that HPV was a common STI (68.2%; Table 3) infecting both men and women (84.1%), and that it can cause cancer (70.5%) was common; however, a lower percentage was aware that HPV can cause anal warts (53.4%). But knowledge of anal cancer was much lower. Few were aware that anal sex increases the risk of anal cancer (21.6%) or that HIV infection increases risk (25.0%). Knowledge that HPV vaccination can prevent anal cancer was also not widely known (21.6%); however, this varied by HPV vaccine status (p < 0.01). A larger percentage of those who had previously initiated HPV vaccination, compared to those who had not, were aware that HPV vaccination prevented anal cancer (41.4% vs. 11.9%, p < 0.01). But this was still less than half of those vaccinated.

Table 2.

Characteristics of the study sample (N = 88)

		Ever Initiated HPV Vaccination
	Total N (%)	Yes %	No %	p-value
Total		33.0	67.1
Age				0.02
18–26	28 (31.8)	50.0	50.0
27–45	60 (68.2)	25.0	75.0
Gender				0.98a
Cisgender man	68 (77.3)	35.3	64.7
Cisgender woman	5 (5.7)	20.0	80.0
Transgender man	1 (1.1)	0	100.0
Transgender woman	6 (6.8)	33.3	66.7
Non-binary	7 (8.0)	28.6	71.4
Another gender	1 (1.1)	0	100.0
Sexual identity				0.17a
Straight	5 (5.7)	0	100.0
Gay/Lesbian	63 (71.6)	33.3	66.7
Bisexual/Pansexual	17 (19.3)	47.1	52.9
Another identity	3 (3.4)	0	100.0
Ethnoracial identity				0.90a
White, non-Hispanic	46 (52.3)	34.8	65.2
Black, non-Hispanic	14 (15.9)	28.6	71.4
Hispanic/Latino	9 (10.2)	22.2	77.8
Another/multiple identities	19 (21.6)	36.8	63.2
Health Insurance				0.67a
Uninsured	4 (4.6)	25.0	75.0
Public	30 (34.1)	26.7	73.3
Private	54 (61.4)	37.0	63.0
Educational attainment				0.12
High school	12 (14.0)	8.3	91.7
Some college/vocation	23 (26.7)	34.8	65.2
4-year college degree or higher	51 (59.3)	39.2	60.8
Medical home				0.76a
No	15 (17.1)	26.7	73.3
Yes	73 (83.0)	34.5	65.8
Medical home is at this FQHC				0.80
No	35 (39.8)	31.4	68.6
Yes	53 (60.2)	34.0	66.0
Currently taking PrEP				0.34
No	17 (19.5)	23.5	76.5
Yes	70 (80.5)	35.7	64.3
Past year HIV test				0.98a
No	6 (6.8)	33.3	66.7
Yes	82 (93.2)	32.9	67.1

Note. Row percentages are reported. Bolded p-values indicate p < 0.05

^aFisher’s Exact Test

Table 3.

HPV and anal cancer knowledge among PrEP patients (N = 88)

		HPV Vaccine Initiation
	Total N (%)	Yes %	No %	p-value
		33.0	67.1
HPV Knowledge
HPV infection common among most sexually active people	60 (68.2)	69.0	67.8	0.91
HPV can cause cancer	62 (70.5)	82.8	64.4	0.08
Males can get HPV	74 (84.1)	93.1	79.7	0.13a
HPV can cause anal warts	47 (53.4)	55.2	52.5	0.82
HPV can be cured with medication (false)	37 (42.1)	48.3	39.0	0.41
HPV transmitted through skin-to-skin contact without fluids like blood or semen	43 (48.9)	58.6	44.1	0.20
Anal Cancer Knowledge
Anal sex increases risk	19 (21.6)	31.0	17.0	0.13
Smoking cigarettes increases risk	24 (27.3)	20.7	30.5	0.33
HPV causes anal cancer	32 (36.4)	48.3	30.5	0.10
HIV infection increases risk	22 (25.0)	31.0	22.0	0.36
HPV vaccination can prevent anal cancer	19 (21.6)	41.4	11.9	< 0.01

Note. Column percentages are reported. Bolded p-values indicate p < 0.05

^aFisher’s Exact Test

Nearly half (49.2%) of unvaccinated respondents indicated they probably or definitely will get their first HPV shot within the next 12 months (Table 4). Importantly, when asked in a follow-up question about the likelihood of getting the first shot if it were offered during their next PrEP appointment, there was a 69.0% increase in the number of respondents responded probably or definitely. Offering HPV vaccination during PrEP visits was perceived as convenient (90.6%), making vaccination easier (88.7%), and increasing the likelihood of vaccination (88.7%) for a majority of participants.

Table 4.

Differences in HPV vaccine intentions based on cost, accessibility, and convenience among unvaccinated PrEP patients (N = 59)

	n (%)
Percent definitely or probably likely to initiate HPV vaccination within 12 months Conditional factors likely to increase HPV vaccination	29 (49.2)
Percent very likely or likely if offered at next PrEP appointment	49 (86.0)
Percent very likely or likely if offered next time tested for HIV	50 (86.2)
Percent agreed that being able to get the HPV vaccine during my next PrEP appointment (i.e., that is getting vaccinated when you see a doctor about PrEP) would:
…be convenient for me	48 (90.6)
…make no difference to me	12 (22.6)
…make it easy for me	47 (88.7)
…increase the possibility that I would get vaccinated	47 (88.7)

The majority of unvaccinated participants were previously aware of HPV vaccination (67.8%; Table 5), but a minority were aware they were currently eligible for HPV vaccination (23.7%). Awareness of HPV and HPV vaccination did not differ between vaccine age cohort (i.e., 18–26 vs. 27–45). Most (64.4%) strongly/somewhat agreed that they needed more information about HPV vaccination prior to making an informed decision. Specifically, they wanted to know more about their risk for anal cancer (59.3%) and effectiveness of HPV vaccination (59.3%).

Table 5.

Information needs for HPV vaccine decision making among unvaccinated PrEP patients (N = 59)

		Vaccine age cohort
Awareness and perceived information needs	Total %	18– 26 %	27– 45 %	p-value
Aware of HPV	54 (91.5)	92.9	91.1	0.84
Aware of HPV vaccine	40 (67.8)	78.6	64.4	0.51a
Aware eligible for HPV vaccination	14 (23.7)	35.7	20.0	0.29
Need more information about HPV vaccination	38 (64.4)	64.3	64.4	0.99
More information needed about the following before making a decision about HPV vaccination
Risk for anal cancer	35 (59.3)	50.0	62.2	0.42
HPV vaccine efficacy	35 (59.3)	50.0	62.2	0.42
Safety of HPV vaccine	28 (47.5)	50.0	46.7	0.83
HPV vaccine importance	26 (44.1)	42.9	44.4	0.92
Other anal cancer prevention options	21 (35.6)	35.7	35.6	0.99a

Note. Column percentages are report

^aFisher’s Exact Test

There was on average a 52% increase in the probability (prevalence ratio = 1.52; 95% CI: 1.04–2.20) of reporting high vaccine intention (i.e., probably/definitely get first shot during their next PrEP appointment) for every unit increase in perceived benefit (Table 6). No other IMB construct was associated with high vaccine intention.

Table 6.

Information, motivation, and behavioral skills associated with acceptability of HPV vaccination during PrEP management visits (N = 59)

	Total		Acceptability of HPV vaccination at PrEP visit
	Mean (SD)	Scale Rangea	Crude Prevalence Ratiob
Information
HPV Knowledge Index	3.4 (2.0)	0–6	1.06 (0.95–1.18)
Anal Cancer Knowledge Index	1.1 (1.6)	0–5	1.03 (0.92–1.17)
Perceived information needs	3.7 (1.4)	1–5	0.85 (0.66–1.10)
Motivation
Perceived benefit	4.3 (0.7)	1–5	1.52 (1.04–2.20)
Behavioral Skill
Anal cancer prevention self-efficacy	4.4 (0.8)	1–5	1.23 (0.90–1.69)

Note. Bolded prevalence ratios are statistically significant, p < 0.05

^aHigher scores indicate higher levels of the construct

^bNo demographic characteristics were associated with the outcome so crude prevalence ratios are presented

Inter-organizational Environment

PrEP providers and staff used a variety of trusted sources of health information to learn about HPV vaccination and anal cancer (theme 14). These included the Centers for Disease Control and Prevention, the American College of Obstetricians and Gynecologists, UpToDate, and Vaccine.org.

Service Environment

There were two distinct themes related to the service environment. First, funding organizations/agencies for the FQHC set priorities with quality metrics that have not (to date) focused on HPV vaccination (theme 15). The responsibility to report on certain metrics to funders structures clinical interactions. For example, a statewide focus on Hepatitis-A vaccination created a sense of importance toward this vaccine and vaccination rates were tracked accordingly. Also, a new city-wide vaccine registry interfaced with the EMR system, providing important information about vaccine histories for patients seeking care at the FQHC.

Discussion

The results of this mixed methods study suggest that FQHCs could increase the reach and uptake of HPV vaccination for GBM and TGW by integrating and promoting HPV vaccination in existing PrEP care. This conclusion was supported with data from both PrEP patients and providers. The EPIS framework offered a holistic, multi-level view of HPV vaccination at an FQHC and helped to identify key barriers and facilitators across patient, provider and system levels. Additionally, the IMB model helped to identify relevant factors related to patients’ decisions regarding HPV vaccination in the context of PrEP care.

The most significant barrier to integrating HPV vaccination into PrEP care is a lack of focus on vaccination in PrEP management guidelines [39]. Although routinely provided in a primary care setting, PrEP management visits were viewed as specialized and “niche.” And while vaccines, including HPV, are mentioned in the CDCs clinical practice guidelines under “Primary Care Considerations,” they were not routinely a focus for providers seeing adult PrEP patients. Two related drivers of PrEP management visits were the metrics set by funding agencies and EMR templates used to structure PrEP patient visits. Neither the metrics nor the related EMR templates included HPV vaccination.

Poor information diffusion regarding anal and oropharyngeal cancers is also a major barrier. This was reflected in lack of knowledge about these cancers in PrEP patients and providers. Awareness of HPV and the fact that “HPV can cause cancer” was widely understood by PrEP patients. Yet knowledge that “HPV can cause anal cancer” and that “HPV vaccination can prevent anal cancer” was limited. In this study as in previous studies of GBM and TGW, anal cancer is disconnected from mental representation of HPV In these populations at much higher risk of anal cancer, HPV is still largely understood as an issue for people with cervixes. Knowledge that HPV can cause anal cancer was equally reported by participants regardless of HPV vaccination history, alluding to gaps in patient education. This was supported by the qualitative data from providers which suggested that patient-provider discussions around HPV vaccination were limited by lack of knowledge. PrEP providers and staff were less confident in their knowledge of anal and oropharyngeal cancers, in addition to the benefits of HPV vaccination for sexually active adults.

Despite these barriers, offering and promoting HPV vaccination as part of PrEP management visits was highly acceptable among PrEP providers and patients [40]. Multi-level interventions are needed to address patient, provider, and organizational barriers. Based on the findings from this study there are several recommendations that can be made to increase the implementation of HPV vaccination in the context of PrEP care.

Targeted patient education is needed to increase awareness of anal cancer risk factors and prevention strategies. Our findings indicate that increasing perceived benefit of HPV vaccination (e.g., it can prevent anal cancer by preventing new anal HPV infections acquired through receptive anal sex) will likely increase vaccine acceptability during PrEP management visits. In contrast, increasing knowledge without directly connecting that information to the patient’s own behaviors and risk factors is unlikely to change vaccine acceptability. All PrEP patients who engage in receptive anal sex should be aware of their risk of anal HPV infections and anal cancer. This is essential for informed decision-making regarding HPV vaccination.

Targeted education is also needed for PrEP providers and patient navigators. Providers were less confident about their knowledge and ability to accurately communicate information to their patients about anal and oropharyngeal cancers. In addition, providers need tools to help facilitate the shared clinical decision-making recommendation for PrEP patients aged 27 to 45. Patient navigators were least familiar with anal cancer risk and preventive factors. Trainings should address the following: (1) Risk and prevention of anal and oropharyngeal cancers; (2) HPV vaccination of sexually adults taking PrEP; and the (3) Age expanded HPV vaccine recommendations.

These findings also point to several healthcare organizational-level factors that could be used to increase HPV vaccination. As PrEP management visits were described as “niche” in this study, EMR templates used to structure these visits can be updated to include prompts for HPV vaccination and key information about anal cancer risk factors. At a minimum, including HPV vaccination status in the EMR template used to manage PrEP patients will likely affect patient-provider discussions. Connecting clinic EMRs to local Immunization Information Systems can also help to ensure accurate HPV vaccination status and improve coordinated care for GBM/TGW who receive sexual health services separate from their primary healthcare [30].

More direct EMR-based alerts have been shown to be effective in other contexts. EMR alerts have been used to successfully increase HPV vaccine initiation among college-aged males [41] and have been successfully implemented at FQHCs to increase adolescent HPV vaccination [42]. The use of EMR alerts to increase targeted HPV vaccination among GBM, however, has not been previously explored.

There were several additions or adaptations to existing organizational processes and events that can also help to facilitate implementation of HPV vaccination protocols in the PrEP context. Delivering trainings and increasing awareness through weekly case conferences and HPV vaccination specific events (e.g., International HPV Awareness Day, Anal Cancer Awareness Day) are clinic-wide strategies that can be targeted to PrEP providers, staff, and patients. Designating an “HPV vaccination champion” can help improve adherence and maintain improvements in vaccine rates [43]. Unique to the PrEP context, leveraging PrEP patient navigators to provide anal cancer education to PrEP patients can be integrated into the sexual health education already being provided by these patient navigators and can also overcome time constraints reported by the PrEP prescribing providers.

Finally, outside organizations can also have a wide-ranging and significant impact on the implementation of HPV vaccination at FQHCs. For example, local, state, and federal funding agencies should prioritize HPV vaccination and require metrics around progress. Professional organizations that disseminate PrEP management guidelines (e.g., Centers for Disease Control and Prevention, local and state public health departments) should emphasize anal cancer prevention through HPV vaccination.

The findings and recommendations provided as part of this study are limited by the focus on a single FQHC. And while we were able to interview the majority of PrEP staff and providers, there was a low response rate from PrEP patients which may limit the external validity of the findings. In addition, we did not interview stakeholders outside of the clinic setting. The perspectives of a wide range of stakeholders (e.g., staff from city and state departments of health and funding agencies) is needed in order to fully understand how HPV vaccination can be promoted alongside PrEP.

Integrating HPV vaccination into PrEP care at FQHCs may increase the reach of anal cancer prevention to diverse sexual and gender minority populations. We have outlined the key barriers identified through a mixed methods study of PrEP patients and providers at an FQHC in a major urban city in the U.S. These findings were used to identify several actionable changes that can be implemented at FQHCs and other clinics providing HIV prevention services to SGM populations.