Human Papillomavirus Vaccination Status and Correlates Among Mid-Adult Women: Connecticut, USA, 2016–2019

Abstract

Background:

In 2019, the CDC expanded their recommendations for human papillomavirus (HPV) vaccination beyond age 26 years to include shared clinical decision-making (SCDM) among adults aged 27–45 years (“mid-adults”). The purpose of this study was to describe HPV vaccination status among mid-adult women before the implementation of SCDM for HPV vaccination.

Methods:

A cross-sectional survey was conducted during 2016–2019 in Connecticut, United States, and enrolled women born in 1981 or later (birth cohorts eligible for HPV vaccination). This analysis was restricted to participants aged 27 years and older at the time of the survey. Correlates of vaccination status, sources of vaccine information, and reasons for not receiving the vaccine were examined.

Results:

Among 298 participants, 64.4% had not received HPV vaccine. Other than age (younger age was associated with being vaccinated), no other demographic or behavioral correlates were associated with vaccination. Compared with unvaccinated women, vaccinated women were more likely to have heard about the HPV vaccine from a doctor (odds ratio [OR] = 3.45, 95% confidence interval [CI]: 2.00–5.88) and less likely to have heard about it from television (OR = 0.23, 95% CI: 0.13–0.41). The main reasons for not being vaccinated were “vaccine not offered” (48%) and “too old” (40%).

Conclusions:

A majority of mid-adult women in this study were not previously vaccinated against HPV, signaling the large opportunity for SCDM with this population. This may be facilitated by ensuring health care providers and mid-adult women know about the availability and potential benefits of HPV vaccination to inform decision making.

Introduction

In August 2019, the Advisory Committee on Immunization Practices (ACIP) expanded their recommendations for human papillomavirus (HPV) vaccination beyond age 26 years to include a shared clinical decision-making (SCDM) recommendation for adults aged 27–45 years (“mid-adults”) in the United States.¹ The American College of Obstetricians and Gynecologists has also updated their recommendations, stating that for some unvaccinated mid-adult women aged 27–45 years, SCDM may be used for HPV vaccination based on the patient's risk for acquiring new HPV infection and whether the vaccine may provide benefit.² These updated recommendations follow expanded approval from the Food and Drug Administration to license the nine-valent HPV vaccine (Gardasil-9; Merck) for men and women in the United States through age 45 years.

The ACIP decision not to recommend routine HPV vaccination for all mid-adults was intended to balance potential individual benefits with the cost of vaccination and lower public health benefit for adults that result in less favorable cost-effectiveness estimates compared with adolescents. Although prior infections may provide protection by natural immunity, very few mid-adult women will have acquired all HPV types targeted by the nine-valent vaccine currently in use in the United States. Thus, some people in this age group may benefit from vaccination if they are susceptible to new HPV infections (i.e., not previously exposed or immunized). However, HPV infections are often acquired during adolescence and young adulthood, and risk for new infections is lower among older age groups.³ Thus, the effectiveness of this prophylactic vaccine is maximized when given before exposure through sexual behavior, on-time vaccination starting as early as age 9 years, with routine immunization at 11–12 years old.

In the United States, HPV vaccination coverage is suboptimal among adolescents (76.9% in adolescents 13–17 years of age in 2021) and even lower among young adults (53.6% in women 18–26 years of age in 2018).^4,5 Little is known about current HPV vaccination coverage among women 27–45 years old who may benefit from HPV vaccine and the SCDM recommendation. We present data on HPV vaccination status, correlates, knowledge, and barriers in a sample of mid-adult women before the implementation of SCDM guidelines.

Methods

The present analysis utilizes data obtained from women who were enrolled in an ongoing population-based case–control study of HPV vaccine effectiveness being conducted in New Haven County, Connecticut, United States, between April 2016 and December 2019. Methods have been previously described.⁶ In brief, eligibility for the parent study included a birth year of 1981 or later to ensure that women had been eligible for the HPV vaccine by having been age 26 years or younger in 2006 when vaccination was first approved for this age group. In addition, participation was restricted to women aged ≤39 years (ages for whom early vaccine impact would be observed in the years following introduction). Cases were women with biopsy-confirmed cervical intraepithelial neoplasia grades 2, 2/3, or 3 or adenocarcinoma in situ and were identified from a population-based surveillance registry. Control participants were women who were identified as having had a normal cervical cytology.

Controls were matched to cases by age, date of testing, and medical practice. Participants completed a survey to ascertain demographic and behavioral information, as well as knowledge about HPV infections and HPV vaccination. After completion of the survey, investigators reviewed the participant's medical records to ascertain clinical information, including provider-verified dates of prior HPV vaccination. Previous analysis indicated high reliability of self-report.⁷ However, in instances of disagreement, we relied on provider-verified records as is carried out in national immunization surveys (e.g., NIS-Teen).

This analysis was restricted to control participants (i.e., those with normal cervical cytology). We further restricted inclusion to women aged 27 years or older at the time of their enrollment visit to focus on the women who became age-eligible for HPV vaccination under the 2019 SCDM recommendations. Reasons for not being vaccinated were examined among women who self-reported not being vaccinated. This study is approved by the Human Research Protection Program Institutional Review Board at Yale University School of Medicine's (Protocol No. 1502015308). All work was performed in accordance with the Declaration of Helsinki, the Belmont Report, and US CFR Title 45 Part 46. Written informed consent was obtained from all study participants.

We compared demographic and sexual history factors between women who were vaccinated as verified in medical records and women who were not unvaccinated. Using logistic regression models, we estimated odds ratios (ORs) for all correlates, with vaccination status as the main outcome. Age was included as a continuous variable in years. The other quantitative variables analyzed (household income, and lifetime number of sex partners) were categorized using a priori cutpoints. Participants with missing data for a given variable were excluded from analyses including that variable. Using multivariable logistic regression, we estimated adjusted odds ratios (aORs) that controlled for all covariates with unadjusted ORs that had p < 0.2 regardless of their significance in the adjusted model.

We also explored knowledge about HPV vaccine, sources of information, and reasons for not receiving the HPV vaccine among unvaccinated women who were age-eligible for vaccination since 2007 and self-reported no history of HPV vaccination. All analyses were conducted using SAS 9.4. (SAS Institute, Cary, NC).

Results

A total of 298 women aged 27–39 years were enrolled as controls (women with a normal Pap smear results regardless of vaccination status) in the parent case–control study between April 2016 and December 2019 and included in this analysis (70% of 423 eligible women). The mean age was 33 years (standard deviation 3.0 years). The majority of women had a college degree (n = 178, 59.7%) and had private health insurance (n = 207, 69.5%), as given in Table 1. The sample was diverse regarding race/ethnicity with self-reported identities as follows: 51.3% white (n = 153), 17.8% Hispanic (n = 53), 17.8% Black (n = 53), and 10.7% mixed/other (n = 32) race/ethnicities. Nearly all women reported having ever been sexually active (n = 275, 92.3%), and 48.3% reported using condoms rarely or never (n = 144).

Table 1.

Characteristics of Study Population and Associations with Being Vaccinated^a

	Vaccinated (n = 106)	Unvaccinated (n = 192)	OR (95% CI)	aORb (95% CI)
Age mean (range)	31 (27–38)	34 (27–39)	0.72 (0.66–0.80)	0.72 (0.64–0.81)
Race/ethnicity, n (%)
White	62 (59.6)	91 (48.7)	1.00
Black	16 (15.4)	37 (19.8)	0.63 (0.32–1.23)
Hispanic	14 (13.5)	39 (20.9)	0.53 (0.26–1.05)
Other/mixed	12 (11.5)	20 (10.7)	0.88 (0.40–1.92)
Education, n (%)
≤HS graduate	19 (18.3)	35 (18.3)	0.99 (0.52–1.89)
Some college	22 (21.2)	41 (21.5)	0.98 (0.54–1.79)
≥College graduate	63 (60.6)	115 (60.2)	1.00
Household income, n (%)
<$50,000	65 (67.0)	104 (58.8)	1.00	1.00
≥$50,000	32 (33.0)	73 (41.2)	0.70 (0.42–1.18)	1.35 (0.69–2.63)
Insurance, n (%)
Private	75 (75.0)	132 (72.1)	1.00
Public	22 (22.0)	44 (24.0)	0.88 (0.49–1.59)
Uninsured	3 (3.0)	7 (3.8)	0.75 (0.19–3.03)
Sexual activity (ever), n (%)
Not sexually active	1 (1.0)	2 (1.1)	0.76 (0.07–8.33)
Condoms all/most	52 (53.6)	79 (43.7)	1.00
Condoms rarely/never	44 (45.4)	100 (55.3)	0.67 (0.41–1.10)
Lifetime number of sex partners, n (%)
1	23 (26.7)	55 (33.1)	0.64 (0.29–1.39)	0.77 (0.32–1.85)
2–3	15 (17.4)	43 (25.9)	0.53 (0.23–1.25)	0.54 (0.20–1.45)
4–5	17 (19.8)	26 (15.7)	1.00	1.00
≥6	31 (36.1)	42 (25.3)	1.12 (0.52–2.44)	1.30 (0.54–3.13)
Prior STI, n (%)
Yes	23 (24.2)	28 (15.6)	1.00	1.00
No	72 (75.8)	151 (84.4)	0.58 (0.31–1.08)	0.59 (0.28–1.23)

^a Frequency distributions may not add to column totals owing to missing data. The proportions that are presented are calculated based on non-missing data and may not add to 100% because of rounding.

^b Covariates in the adjusted model are those that had value of p < 0.20 in the unadjusted model and include age, household income, lifetime number of sex partners, and prior STI. Bold indicates p-value <0.05.

CI, confidence interval; HS, high school; OR, odds ratio; STI, sexually transmitted infection.

In this sample, 64.4% (n = 192) had not received HPV vaccine. With increasing age, women were less likely to be vaccinated (OR = 0.72, 95% CI: 0.66–0.80; aOR = 0.72, 95% CI: 0.64–0.81). No other factors were associated with vaccination status in adjusted analyses.

A large majority of women had heard of HPV vaccine (n = 262, 92.9%; Table 2). This proportion was higher among women who had been vaccinated (98.1%) compared with those who had not been vaccinated (89.9%, OR = 5.56, 95% CI: 1.28–25.0). Sources of information about HPV vaccine also varied by vaccination status. Compared with unvaccinated women, vaccinated women were more likely to have heard about the HPV vaccine from a doctor (OR = 3.45, 95% CI: 2.00–5.88) and less likely to have heard about it from television (OR = 0.23, 95% CI: 0.13–0.41). Most women answered HPV knowledge questions correctly regardless of vaccination status, with one exception: vaccinated women were more likely to know that HPV causes genital warts compared with unvaccinated women (OR = 4.35, 95% CI: 2.33–8.33).

Table 2.

Human Papillomavirus-Related Factors Among Study Population and Association with Being Vaccinated^a

	Vaccinated (n = 106)	Unvaccinated (n = 192)	OR (95% CI)
Ever heard of HPV vaccine
Yes	101 (98.1)	161 (89.9)	5.56 (1.28–25.0)
Sources of information about HPV vaccine
Doctor	81 (78.6)	92 (51.4)	3.45 (2.00–5.88)
Television	17 (16.5)	83 (46.4)	0.23 (0.13–0.41)
Magazine	13 (12.6)	33 (18.4)	0.64 (0.32–1.28)
Friends	17 (16.5)	37 (20.7)	0.76 (0.40–1.43)
Family	23 (22.3)	25 (14.0)	1.75 (0.94–3.33)
School	22 (21.4)	29 (16.2)	1.41 (0.76–2.63)
Correct knowledge about HPV
HPV is an STI	83 (79.8)	149 (80.1)	0.98 (0.53–1.79)
HPV affects men and women	96 (91.4)	160 (86.5)	1.67 (0.75–3.70)
HPV can be asymptomatic	87 (83.7)	153 (82.3)	1.10 (0.58–2.08)
HPV causes genital warts	90 (86.5)	109 (59.2)	4.35 (2.33–8.33)
Reasons for not receiving HPV vaccineb
Not offered/recommended	n/a	53 (48.2)	—
Too old	n/a	44 (40.0)	—
Not at risk for HPV	n/a	11 (10)	—
Safety concerns	n/a	7 (6.4)	—

^a Frequency distributions may not add to column totals owing to missing data. The proportions that are presented are calculated based on non-missing data and may not add to 100% because of rounding.

^b n = 110 for normal cytology (women age-eligible for vaccination since 2007 and self-reported no history of HPV vaccination).

HPV, human papillomavirus; n/a, not applicable.

The main reasons for not receiving the HPV vaccine among those who self-reported that they had not been vaccinated (n = 192) were as follows: the vaccine was not recommended to them (48.2%), they thought they were too old for vaccination (40.0%), no perceived risk (10.0%), and safety concerns (6.4%). All other reasons (e.g., lack of endorsement by friends or family, dislike of needles) were reported infrequently (<5%).

Discussion

These results indicate that the majority (>60%) of women aged 27–39 years with recent normal cervical cytology were not vaccinated against HPV at the time of study participation, highlighting the substantial opportunity for clinicians and mid-adult patients to have meaningful discussions and make shared decisions about the HPV vaccine under the 2019 guidance from ACIP for this age group. Although most women had heard about HPV vaccine, those who had heard about it from their clinician were more likely to have been vaccinated. This may reflect the importance and value of conversations with clinicians in choosing to be vaccinated in this age group. For adolescents, the important role that health care providers play in HPV vaccine acceptance among their patients has been well documented, and there is evidence for this in adult populations as well.^8–10 Furthermore, the main reason for not being vaccinated was that it had not been recommended by a clinician; this does not need to be an obstacle going forward under current SCDM recommendations from ACIP.

Recent studies have shown HPV vaccination is acceptable to many women in this age range. In one study, 50% of women aged 27 and older in a clinic-based study reported that they would want HPV vaccine.¹¹ Another study found mean HPV vaccine acceptability scores from 60 to 65 on 100-point scale of among adult women when the vaccine is provided at no cost.¹² Of note, the out-of-pocket cost for the vaccine was the most salient barrier reported in this study; under the new recommendation for SCDM, the cost of the vaccine is generally required to be covered by health insurance without cost sharing.¹³ All women in this study were seeking reproductive health care (i.e., had recent Pap smear), and these visits could be an opportunity for HPV education and vaccination of mid-adult women. At these types of visits, it might not be overly burdensome to engage in SCDM in a way that is incorporated into primary care and overall sexual reproductive health.

The current ACIP and ACOG recommendations are that HPV vaccination can be “recommended for some adults,” but that “HPV vaccination does not need to be discussed with most adults.”^1,2 However, no further guidance on which mid-adults may benefit from SCDM is provided. On the one hand, women with fewer lifetime sex partners may have a greater potential for benefit because of a lower likelihood of prior HPV infections, yet women with more lifetime sex partners may be at higher risk for acquiring future HPV infections. At any age, having a new sex partner is a risk factor for acquiring a new HPV infection, and this does occur in mid-adults.^14,15 Tools to predict the probability of acquiring a new HPV infection based on behaviors and other factors could be useful aids for identifying the population that would be most likely to benefit from SCDM and future research could explore this.

In the meantime, given difficulties anticipating the acquisition of new sex partners and subsequent risk for HPV infections and the lack of identified correlates in this study, discussion about HPV vaccination with many if not most mid-adult patients should be considered. Furthermore, there are some indirect benefits to be gained from broadly engaging in SCDM. Recommending that HPV vaccine be routinely discussed with most mid-adults may reduce inequities and biases in SCDM, would align with preventive health messaging, and would facilitate the integration of HPV vaccine counseling skills into routine clinical practice.

This new opportunity also presents challenges related to the implementation of SCDM for vaccination. SCDM is generally appropriate when the potential benefits for a clinical course of action do not clearly outweigh possible risks at the individual level, or when there are tradeoffs between benefits and risks for different options making patient preferences and values an important part of the decision-making process.^16–18 In the United States, very few vaccine recommendations from ACIP involve SCDM, and it is not clear how this should be operationalized in practice because safety and efficacy for all recommended vaccines are well-established, thus conferring a favorable risk–benefit ratio at the individual level. ACIP policy recommendations are further informed by societal cost-effectiveness analysis, and expanding the age of HPV immunization will result in substantially higher costs to society than the current recommendation while producing small additional population-level health benefits.¹⁹ Therefore, balancing the individual level benefit with societal costs may be a challenge in clinical practice.

This study has several limitations to note. It may have limited generalizability as it utilizes data obtained from a case–control study based in a single county in Connecticut. In addition, the study does not represent a general population as only controls from the parent case–control study were included and may represent a patient population with fewer risk factors for cervical neoplasia or more robust preventive health practices, including immunization. With the latter, our study may overestimate the proportion of mid-adult women who were vaccinated with the HPV vaccine. Furthermore, this study was conducted during the 3 years (2016–2019) before SCDM guidance from ACIP, and some participants may have been vaccinated after their study visit. Finally, our study did not include men for whom SCDM also applies in the mid-adult age range. Despite these limitations, notable strengths of our study include a racially and ethnically diverse patient sample and robust vaccination history ascertainment using provider-verified medical records.

Conclusions

Although there is limited guidance at present on how to use SCDM for HPV vaccination in mid-adult populations, this recent recommendation does present a new opportunity for adults in the United States. At a minimum, clinicians and patients should be aware of the new recommendation to allow for SCDM to take place. For mid-adult women to determine if vaccination is their preferred course of action, they should know about their options and the potential benefits, risks, and limitations of immunization so that they can make an informed decision. Further research is needed to identify the best way to educate patients and providers about this recommendation and to support effective conversations to allow a true shared decision-making process to take place.

Authors' Contributions

S.S.S. conceptualized analysis and led to article writing, N.P.J. conducted data analyses, E.L.S. and A.R.T. performed day-to-day oversight of study protocols and data collection and management, C.R.O. conceptualized study design and maintained oversight of study implementation, L.M.N. conceptualized study design, acquired funding, maintained oversight of study implementation, contributed to article writing and analytic plan. All authors read and approved the final article.

Author Disclosure Statement

S.S.S. receives HPV vaccine as a “drug only” grant from Merck for a research study and has previously been a consultant for Merck. L.M.N. serves as a scientific advisor to Merck. All other authors (C.R.O., E.L.S. and A.R.T., and N.P.J.) have no potential conflicts or disclosures.

Funding Information

This work was supported, in part, by the National Institutes of Health, Grant Nos. R01AI123204 (L.M.N., S.S.S., C.R.O.), K07CA230234 (S.S.S.), and KL2TR001862 (C.R.O.).