Pediatric hematology and oncology physician and nurse practitioner views of the HPV vaccine and barriers to administration

ABSTRACT

Rates of Human papilloma virus (HPV) vaccination among pediatric survivors of cancer and patients with sickle cell disease are lower than the national average. While recent attention has focused on patient HPV vaccine hesitancy and refusal, less is known about provider-level and system-level barriers to vaccinations in pediatric hematology/oncology (PHO) populations. Applying thematic analysis to qualitative interviews with 20 pediatric hematology/oncology physicians and nurse practitioners, we examine their views regarding HPV vaccination, with a focus on access and barriers to providing HPV vaccination in PHO practices. Results demonstrated that despite 90% of interviewees supporting HPV vaccination in their population, the number of pediatric hematology/oncology providers who reported that they counsel about HPV or provide HPV vaccination was 45%, even in stem cell and sickle cell clinics, where other childhood vaccines are commonly provided. Clinicians identified provider-level, clinic-level, and system-level barriers to giving the HPV vaccination, including but not limited to time/flow constraints, lack of resources, and continued education regarding the HPV vaccine. These barriers impede the ability for pediatric hematology/oncology providers to counsel and provide HPV vaccination to this specialized population.

Introduction

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States, with an estimated 43 million infections in 2018. Prior to the introduction of HPV vaccination, there were roughly 14 million new HPV cases annually, with nearly half occurring in those ages 15–24 y.¹ While most individuals do not progress to HPV-related diseases, HPV persistence places individuals at risk for the development of cervical, vulvar, vaginal, anal, oropharyngeal, and penile cancers. Each year, HPV-related cancers affect 31,500 individuals in the US.¹ The large majority of HPV-associated malignancies are vaccine preventable. The first HPV vaccine (Gardasil) covered four HPV types and was approved by the US Food and Drug administration (FDA) in 2006 for females ages 9–26, with expansion to include males in 2009. The HPV vaccine currently available in the United States (US) is the 9-valent vaccine (9vHPV), which protects against the two HPV types most frequently associated with the development of genital warts (types 6 and 11) and the seven HPV types most frequently associated with cervical and other HPV-related cancers (types 16, 18, 31, 33, 45, 52, and 58). The vaccine is currently approved for use in individuals ages 9–45 y and is recommended by the Advisory Committee for Immunization Practices (ACIP) for routine vaccination at age 11 or 12 y (recently the ACIP determined that routine vaccination can begin at age 9 y) and routine catch-up through age 26 y. Despite over 15 y of post-marketing surveillance demonstrating safety and efficacy, HPV vaccination rates in the US remain suboptimal with only 61.7% of adolescents in general receiving the recommended 2- or 3-dose regimen in 2021.^1,2

HPV vaccination is important for pediatric hematology and oncology (PHO) populations. The safety and immunogenicity of HPV vaccination in pediatric, adolescent and young adult (AYA) cancer survivors was confirmed in a single arm, open-label, phase II trial in 2021.³ While the most common cause of death in pediatric cancer survivors remains recurrence of the primary disease in 56%, the second most common cause (15–19%) is due to secondary or subsequent neoplasms.^4,5 When compared with the general population, female pediatric/young adult cancer survivors have a 40% relative excess of all HPV-related malignancies and for males the relative excess is 150%.⁶

The HPV vaccine is similarly important for patients with sickle cell disease. The majority of individuals living in the US with sickle cell disease (SCD) are Black or African American, a minoritized population known to experience significant health inequities, particularly as it relates to several types of HPV-related cancers.^7–9 As survival to adulthood in SCD has improved, individuals with SCD have prioritized their sexual and reproductive health (SRH), yet access and education related to SRH remains inconsistent.^10,11 Thus, focused efforts for HPV vaccination in both PHO populations are of the utmost importance.

Low HPV vaccination rate in PHO patients is a problem across institutions. A study of 982 pediatric cancer survivors in five National Cancer Institute (NCI) designated comprehensive cancer centers showed initiation of HPV vaccination among adolescent cancer survivors to only be 22% when compared to their peers at 42.5%.¹² A western New York retrospective review of 312 patients diagnosed with cancer at under 10 y old found that only 43.5% (27/62) males and 55.1% (43/78) of females had completed the three-dose vaccine series.¹³

A major factor in the poor uptake of HPV vaccine among PHO patients appears to be the lack of a provider recommendation. In the study by Klosky, et al., 72% of the 982 participants cited no provider recommendation regarding the HPV vaccine.¹² Of those, only 5% started the vaccine series. However, in the remaining 28% of the 982 participants who were recommended to receive HPV vaccination, half reported initiating the series. In another cross-sectional survey of 955 pediatric cancer survivors, 73% of participants did not receive a provider recommendation for HPV vaccination.¹⁴ Patient-level factors associated with absence of a recommendation included perceived lack of insurance coverage for HPV vaccine, identifies as male, and decreased parent-survivor communication regarding the HPV vaccine.¹⁴ Reasons for poor uptake of HPV vaccination specific to patients with sickle cell disease are not widely known, though several studies have documented low rates of influenza and other vaccines in this patient population thought to be related to low provider knowledge and lack of recommendation.^15–17

Clinic- and system-level barriers have also been previously identified that impair the ability of providers to implement HPV vaccination programs. The most common barriers cited by providers include the electronic medical record system (EHR), training and education, tools and resources, as well as provider champions to implement HPV VAC (vaccinate adolescents against cancer) programs.¹⁸ Other barriers identified by this project included staffing limitations, difficulties with state immunization registries, patient misinformation surrounding the HPV vaccine itself, cultural barriers, competing priorities, levels of funding, staff buy-in, training needs, and low health literacy.¹⁸

Despite these data showing that provider recommendation increases vaccination rates, there have been relatively few studies published on the attitudes and practices of hematology/oncology providers with respect to HPV vaccination. Existing survey data suggests both low rates of HPV vaccine counseling or ability to provide HPV vaccination by pediatric subspecialists generally and pediatric oncologists specifically.¹⁹ Less is known about providers' perceptions and lived experiences related to HPV vaccine counseling and access. The purpose of this study, therefore, was to assess via in-depth interview, physician and nurse practitioner views regarding HPV vaccination, with a focus on access and barriers to providing HPV vaccination in PHO practices.

Methods

Participants/Procedure

As part of a state-wide study of PHO subspecialty provider vaccination practices, all 30 practicing PHO providers in the state of Indiana were invited via in-person communication or e-mail to participate in a 30-min interview study assessing provider attitudes toward vaccination, including HPV vaccination. Eighteen physicians and two nurse practitioners (response = 66.7%) completed one-on-one qualitative interviews. Participants worked in a wide variety of clinical settings, including dedicated clinics focusing on leukemia/lymphoma, bone marrow transplant (BMT), sickle cell disease, and solid tumor/neuro-oncology, as well as more generalized hematology/oncology practices. Individuals were provided a study information sheet, and electronic consent was obtained prior to the interview. The interview guide was based on the literature on HPV vaccination and adapted from qualitative interview guides previously used in provider HPV vaccine research by one of the authors (G.D.Z.).^20–22 The interview guide was refined during the first 3–5 interviews, with questions that were not salient dropped and, when more detail was preferred, additional probing questions added (Supplemental Material). Due to the COVID−19 pandemic, 19 interviews were conducted remotely via Zoom and one in person. This study was approved by the Indiana University Institutional Review Board (IRB Protocol #2010192007).

Data collection

The interviews took place from January 2021 to March 2021. Demographic information on participants’ gender, race/ethnicity, age, workplace organization, as well as years in practice was collected via a brief electronic survey. While attitudes regarding multiple vaccines were assessed during the interviews, this paper focuses solely on HPV vaccination. Participants were asked about their attitudes toward the HPV vaccine, patients and/or their family’s concerns/misconceptions toward the HPV vaccine, and barriers to HPV vaccination in pediatric hematology/oncology clinics.

Interviews were audio-recorded and transcribed. During each individual interview, the interviewer took notes and completed a field note after the interview. The authors were all in agreement that the 20 completed interviews reached theoretical saturation, with little new themes/perspectives emerging regarding HPV vaccination on the later interviews.²³

Analysis

We used a thematic approach to analysis.²⁴ A codebook was created based on a literature review and re-occurring themes encountered during an initial review of transcripts. Each transcript was coded by two authors, with differences resolved by discussion. Example codes included provider attitudes to HPV vaccine, provider HPV vaccine concerns, provider-level barriers to HPV vaccine, institution-level barriers to HPV vaccine, and provider HPV vaccine counseling.

Results

Participants

Of the 20 interviewees, 65% identified as female and 35% identified as male (see Table 1). Eighty-five percent of those interviewed self-identified as white, 10% as black, and 5% as Latino. Sixty percent of respondents were early career, between ages 31–40 y, with the remainder mid-late career. Additionally, 65% had practiced in their subspecialty for ≤10 y. 90% were from the large children’s hospital in central Indiana, and 10% were from outside organizations or regional health systems. We initially compared sickle cell and general PHO providers with oncology-specific pediatric providers but did not observe differences between the groups; so, we present the data together.

Table 1.

Participant demographics.

Demographics	n = 20(%)
Gender
Male	7 (35%)
Female	13 (65%)
Race/Ethnicity
White	17 (85%)
African American	2 (10%)
Latinx/Hispanic	1 (5%)
Age
20–30	1 (5%)
31–40	12 (60%)
41–50	5 (25%)
51–60	0 (0%)
61–70	2 (10%)
Focus of pediatric heme/onc practice
General Hematology/Oncology	4 (20%)
Oncology (solid tumor/lymphoma)	4 (20%)
Oncology (CNS tumors)	2 (10%)
Oncology (leukemia)	1 (5%)
Oncology (survivorship)	2 (10%)
Oncology (BMT)	2 (10%)
Hematology (hemoglobinopathies)	3 (15%)
Hematology (hemostasis/thrombosis)	2 (10%)
Years in practicing pediatric Hematology/Oncology
0–5	9 (45%)
6–10	4 (20%)
11–20	5 (25%)
21+	2 (10%)

Overview

Overall, 90% pediatric hematology/oncology clinicians described HPV vaccination as important for their patient population. Sixty-five percent explicitly stated having no concerns regarding HPV vaccine in general; the remaining seven did not state any concerns regarding the vaccine. The most common rationale for HPV vaccination was for cancer prevention (80%), with a subset of providers clarifying that pediatric hematology/oncology populations are more at risk for subsequent cancers (25%).

The majority (n = 15, 75%) felt that HPV vaccination should fall under the responsibility of the primary care physician (PCP), with a smaller subset (n = 4, 20%) stating that it should be the responsibility of both the subspecialty provider and PCP. Typically, only PPSV23, MCV4, MenB, PCV13, and Influenza vaccines are available in our institution’s PHO clinic. Only three providers from outside of our institution reported that they stocked the HPV vaccine in their clinic. When interviewees were asked if they ever discussed HPV vaccination with their patients, (n = 8, 40%) responded no, (n = 7, 35%) responded yes, and (n = 2, 10%) responded rarely. One interviewee commented that not knowing who should take responsibility (PCP vs. subspecialist) for HPV vaccination created a barrier to counseling. Participants additionally identified multiple system-level, clinician-level, and patient-level barriers to HPV counseling and provision. Please see Figure 1 for a schematic of clinician-level and system-level barriers.

Figure 1.

Model of clinician-level and system-level barriers to HPV counseling and provision.

Patient barriers

Despite over 15 y of HPV vaccination being in routine use in community settings, participants noted that they still encounter patient/guardian refusal when they discuss HPV vaccination. Multiple participants reported that one common concern that families have raised was that it would promote sexual activity in their child or was not indicated because their child was not known to be sexually active (n = 6, 30%). Providers also identified parent concerns regarding reactions or side effects as reasons for parent/guardian refusal that participants mentioned (n = 5, 25%). Providers reported that families also held misconceptions about the risk of HPV acquisition from the vaccine (n = 2, 10%). Other reasons subspecialty providers noted for parent/guardian vaccine refusal included it not being a required childhood vaccination in Indiana (n = 2, 10%), religious objections to vaccines (n = 2, 10%), concerns that their child would not be able to mount an immune response to the vaccine (n = 1, 5%), distrust in the government (n = 1, 5%), the vaccine is not needed in boys (n = 1, 5%), the patient is already receiving other vaccinations that day (n = 1, 5%), and the patient being scared of needles (n = 1, 5%).

Other patient/guardian barriers to HPV vaccination encountered by clinicians were related to issues not covered above. For example, some patients travel multiple hours to their subspecialty clinic and so an extra trip to get the HPV vaccine in the subspecialty clinic could create difficulties for patients and their families (n = 1, 5%). Also, one provider noted that some patients are ill during their patient encounter and thus families forgo vaccination during that visit.

Clinician barriers

The most common clinician-level barrier was that subspecialty providers themselves felt that they did not have the latest information to provide appropriate HPV vaccine counseling to patients (n = 7, 35%). One participant noted, “I would need a refresher about the appropriate age groups that get HPV, ‘cause I know sometimes it’s been shifting around a little bit, and then I would probably need a refresher about the more common side effects of the HPV vaccine”-pediatric hematology-oncology fellow. Clinicians frequently did not know what vaccines were stocked in their clinic; “so I don’t even know that we stocked HPV”-pediatric hematologist at outside center. Three participants described a lack of electronic health record (EHR) reminders that HPV was part of the adolescent vaccine schedule, and that HPV vaccination was not being built into the EHR re-vaccination protocols for stem cell transplant patients. Per one participant, “I can tell you right off the bat, what the issue is with our patient population, which is that our post-transplant SOP [standard operating procedures] has not been updated in many, many, many years”-pediatric hematologist specializing in stem cell transplant. Two participants reminded interviewers that patients on active chemotherapy treatment cannot receive vaccinations.

System-level barriers

There were multiple system-level barriers identified that prevent subspecialty clinicians from being able to give the HPV vaccine. The most common were time and clinic flow constraints (n = 12, 60%): “probably time. It’s an extra thing that someone has to do”-pediatric hematology-oncology fellow. This was followed in frequency by the lack of nursing/medical assistant (MA) resources for vaccine administration (n = 7, 35%): “I don’t think it would be my support, it would be more the MA support, support for the clinic in logistics and flow”-pediatric neuro-oncologist. A minority (n = 3, 15%) noted that a lack of vaccine records or difficulty in accessing the state immunization information system created barriers to vaccination.

Another barrier identified was vaccine accessibility (n = 1, 5%): “However, we don’t give HPV vaccination”-pediatric hematologist-oncologist specializing in survivorship. “[Our health system] doesn’t purchase, doesn’t stock the HPV vaccine, at least not at [my location]. We can’t actually give our patients the HPV vaccination in clinic” -pediatric hematologist-oncologist specializing in survivorship. An additional participant mentioned a lack of space to store the vaccine (n = 1, 5%): “I would just say that what we’ve said about a hundred times, that administration needs to be able to find the storage and the people to give the vaccines and educate us on proper timing of everything”-pediatric oncologist specializing in solid tumors. Other systemic barriers mentioned were the cost of the vaccine (n = 1, 5%), and reimbursement (n = 1, 5%).

Discussion

Despite the majority of PHO providers describing the importance of the HPV vaccine at some point in their interview, only a small number regularly discuss HPV vaccination with their patients or have the vaccine available to give to their patients. While provider recommendation has been shown to increase uptake of the HPV vaccine, our participants reported multiple system- and clinician-level barriers to their providing recommended HPV vaccine counseling to patients. These results are similar to those reported by Hoffstetter et al. in which 44% of hematologists/oncologists surveyed sometimes discussed HPV vaccination with their patients sometimes and only 22% always discussed HPV vaccination. Similar to our findings, Hoffstetter et al. describes pediatric subspecialists as conflicted about who is responsible for HPV vaccine – the primary care provider or the subspecialty team.¹⁹

The system and clinician-level barriers identified by our participants provide additional detail to the barriers described by other studies of pediatric subspecialty provider attitudes toward HPV vaccination, including subspecialists having insufficient information about the HPV vaccine, difficulty ensuring vaccine series completion, describing the vaccine as too new, too many vaccines in the adolescent vaccine schedule, and that HPV vaccination may encourage riskier sexual health behaviors. These findings suggest that health care systems bear a sizable part of the responsibility for low levels of HPV recommendations and, by extension, low vaccination access.

A recent article addressed provider-level barriers to HPV vaccination in pediatric/young adult cancer survivors.²⁵ Using qualitative interviews with 13 oncology providers and 11 PCCs (primary care clinicians) from a single institution in a large city, they identified themes that were similar to those that we describe, including HPV vaccination should be the PCP’s responsibility, lack of standard guidelines for HPV vaccination in patients in remission, and logistical barriers such as full schedules. These data were specific to oncology survivorship providers. Our study expands these findings by recruiting providers state-wide, and looking more broadly at all PHO providers beyond those involved with survivorship, including hematologists, general oncologists, and disease-specific providers (e.g. neuroonc, leukemia/lymphoma, solid tumors).

Our findings were consistent with another recent qualitative study of oncology providers.²⁶ In this study, providers cited educational barriers plus complicated post-treatment HPV vaccination guidelines as a barrier to their capability to administration. They also identified time concern barriers in addition to clinical workflow integration concerns. This paper provides additional evidence that these barriers are not limited to a single institution and belies a more widespread problem. Our finding that many PHO providers consider HPV vaccine the general pediatric provider’s domain and that HPV is not consistently emphasized as part of standard post-transplant/post-treatment procedures raises an important contradiction. For children with complex medical illnesses, general pediatric providers typically reference the subspecialists’ guidance for ongoing care. If HPV vaccination, and anti-cancer vaccine, is not included in the standard communication between PHO specialists and PCP, then AYA with cancer or SCD are at risk for not receiving their recommended HPV vaccines.

We found pervasive barriers to HPV vaccination at every level, raising quality of care issues. From the clinician side, barriers involving knowing which vaccines are available in clinic could be easily rectified by having a list of vaccines that are readily available in the office. In the age of electronic medical records, incorporating the available vaccinations into a template or provider reminder prompts would also serve as a reminder to clinicians about vaccination. If vaccines are not available in clinic, incorporating HPV vaccine instructions into standard templates or her dot-phrases for PCP guidance would also be helpful, as the patient’s PCP may not be sure whether or when to resume vaccinations. Finally, addressing clinician education regarding the HPV vaccination could be accomplished by many different routes. This could include having a yearly updated recommended vaccination schedule with timing and number of doses along with other age-appropriate vaccinations available in the workspace. Educational opportunities through institution sponsored CME such as grand rounds, brief educational e-mails, or providing educational materials could also help increase clinician knowledge and comfort with providing HPV vaccination.

Addressing system-level barriers to HPV vaccination must be multifaceted. Many clinicians are forced to limit the amount of time they can spend with patients, restricting time available to discuss preventative care needs, particularly in subspecialty care offices. Yet, studies demonstrate that many children/adolescents with complex medical conditions identify their subspecialist as their primary health care provider, leading to gaps in preventative care.²⁷ Creative approaches might include task-shifting assessing vaccine status and providing vaccine counseling and a strong recommendation to other team members (e.g. nursing, pharmacy). The use of champions or having a specific clinic staff member to educate team members, advocate and take responsibility for the task, has been used successfully in other areas, and may also help alleviate the burden on the subspecialist.²⁸ Other health system barriers, such as ensuring cost of buying the vaccine is feasible for offices and that insurance reimburses for vaccinations given in a subspecialty, would need to be addressed at a level higher than a specific subspecialty.

Limitations

Our providers were all from a single small Midwestern state, predominantly from one large health system, reflecting the distribution of PHO providers across the state. We also recognize the potential for volunteer bias, in that those who agreed to participate in the study may have held stronger beliefs about the role of PHO providers in HPV vaccination than those who declined to participate.

Conclusion

Low vaccination rates in pediatric sickle cell and cancer survivorship populations, coupled with provider-, clinic- and system-level barriers, point to the need for system-wide changes. Despite an overall positive attitude toward HPV vaccination, providers described multiple barriers that impede their ability to make a strong recommendation for or to give HPV vaccinations. Interventions are needed at all levels of health care delivery including patient education on HPV vaccination, clinician education on updates and recommendations regarding HPV vaccination, and increasing time and available man-power to be able to administer the HPV vaccine in clinic

Funding Statement

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA082709-21S2. Additionally, Dr Jacob has received funding through the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number K23HL143162. Similarly, Dr Coven has received funding through the National Institutes of Health under Award Number K12HS026390-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Disclosure statement

No potential conflict of interest was reported by the author(s).