Human papillomavirus (HPV) causes >35 000 cancers each year in the United States,1  yet vaccination rates remain lower than other recommended adolescent immunizations.2  Since adolescents frequently miss well-visits, capturing any visit opportunities for vaccination at acute and chronic care visits is important.35  However, some clinicians are concerned that when children are vaccinated at acute or chronic visits, they may not return for preventive care.6  To address this concern, we analyzed visits in 37 pediatric practices across the United States, hypothesizing that HPV vaccination at acute and chronic primary care visits would have limited or no impact on timeliness of subsequent well-visits.

We performed a retrospective cohort study using 3 years of electronic health record data from 37 pediatric primary care practices in 18 states (October 2015–December 2018, before the coronavirus disease 2019 pandemic) participating in the National Institutes of Health-funded STOP-HPV study, a randomized controlled trial testing a clinician-targeted intervention to improve HPV vaccination.7  We used baseline data before the intervention start. We identified adolescents aged 11-to-17 years with an initial well-visit (subsequently “index visit”) followed by at least 1 acute or chronic visit when an HPV vaccination was due (Fig 1). Using logistic regression-based inverse probability of vaccination (propensity weighting) and then weighted Kaplan-Meier and restricted mean time-to-event methods8  (Supplemental Information), we estimated the association of acute or chronic visit HPV-vaccination with 2 primary outcomes: (1) receipt of well-child care within 18 months of an index well-visit, and (2) time to next well-visit post the 12 month anniversary of the index well-visit (Fig 1). This study was approved or deemed exempt by Institutional Review Boards at the American Academy of Pediatrics, the University of California, Los Angeles, and the Children’s Hospital of Philadelphia.

FIGURE 1

Study timeline. The observation period was the time from the index well-visit (A) to the subsequent well-visit (E). If the child had no subsequent well-visit, the observation ended at 24 months (F). For the first outcome, we evaluated the results at 18 months (D) to reflect timely well-child care receipt.

FIGURE 1

Study timeline. The observation period was the time from the index well-visit (A) to the subsequent well-visit (E). If the child had no subsequent well-visit, the observation ended at 24 months (F). For the first outcome, we evaluated the results at 18 months (D) to reflect timely well-child care receipt.

Close modal

Among the 17 000 adolescents (47% female; 52% 11–12 years; mean (SD) age 12.9 (1.8) years; mean (SD) of 2 (1.5) acute or chronic visits between the index and subsequent well-visit), only 3.3% of 11–12 year olds and 3.0% of 13–17 year olds received an initial HPV vaccine at an acute or chronic visit. Many more, 26.0% of 11–12 year olds and 25.0% of 13–17 year olds, received a second or third (“subsequent”) HPV vaccine at an acute or chronic visit. Across all ages and doses, vaccinating at acute or chronic visits was not associated with a statistically significant reduction or delay in well-visits (Table 1). Only among those 11–12 years who received a subsequent dose of HPV vaccine at an acute or chronic visit were differences statistically significant; 61% of those vaccinated had a well-visit within 18 months of the index well-visit versus 69% for those who did not receive an HPV vaccine at an acute or chronic visit, an 8% point difference (95% confidence interval [CI]: 1.0%–15.0%). This difference represented a 0.50 month (2.63 vs 3.12; 95% CI: 0.12–0.85) delay in time to a subsequent well-visit.

TABLE 1

Receipt of Subsequent Well-visits in the Retrospective Cohort Analysis

Category By Age at Index VisitRMST at 18 mo From Index Visit (HPV not given versus given,) Difference (95% CI)aCumulative Incidence at 18 mo From Index Visit (HPV not given versus given), Difference (95% CI)b
All adolescents, all HPV vaccine doses 2.74 vs 2.93, +0.19 (−0.12, +0.49) 0.66 vs 0.63, +0.02 (−0.03, +0.07) 
11–12 y, initial dose 2.29 vs 2.59, +0.30 (−0.18, +0.79) 0.75 vs 0.68, +0.07 (−0.01, +0.14) 
11–12 y, subsequent dose 2.63 vs 3.12, +0.50 (+0.12, +0.85) 0.69 vs 0.61, +0.08 (+0.01, +0.15) 
13–17 y, initial dose 2.95 vs 2.82, −0.13 (−0.72, +0.46) 0.61 vs 0.65, −0.04 (−0.14, +0.07) 
13–17 y, subsequent dose 3.32 vs 3.46, +0.14 (−0.12, +0.40) 0.55 vs 0.54, +0.01 (−0.04, +0.06) 
Category By Age at Index VisitRMST at 18 mo From Index Visit (HPV not given versus given,) Difference (95% CI)aCumulative Incidence at 18 mo From Index Visit (HPV not given versus given), Difference (95% CI)b
All adolescents, all HPV vaccine doses 2.74 vs 2.93, +0.19 (−0.12, +0.49) 0.66 vs 0.63, +0.02 (−0.03, +0.07) 
11–12 y, initial dose 2.29 vs 2.59, +0.30 (−0.18, +0.79) 0.75 vs 0.68, +0.07 (−0.01, +0.14) 
11–12 y, subsequent dose 2.63 vs 3.12, +0.50 (+0.12, +0.85) 0.69 vs 0.61, +0.08 (+0.01, +0.15) 
13–17 y, initial dose 2.95 vs 2.82, −0.13 (−0.72, +0.46) 0.61 vs 0.65, −0.04 (−0.14, +0.07) 
13–17 y, subsequent dose 3.32 vs 3.46, +0.14 (−0.12, +0.40) 0.55 vs 0.54, +0.01 (−0.04, +0.06) 

Differences have been rounded to the nearest hundredth.

a

RMST: restricted mean survival time in months. Longer times mean more delay in next well-visit.

b

Cumulative incidence: the predicted chances of a well-visit at a given follow-up time, with larger values meaning more children have a well-visit as of the follow-up time.

In this retrospective analysis, 11–12 year olds receiving a subsequent dose of HPV vaccine at an acute or chronic visit had a modest reduction in subsequent well-visits and a small delay in the timing of those well-visits. For adolescents 13–17 years of age, and for initial HPV vaccination at acute or chronic visits in all age groups, we found no decrease in attendance or delay in subsequent well-visits following HPV vaccination. Among all adolescents, vaccination at acute or chronic visits occurred infrequently.

Before this study, little was known regarding whether HPV vaccination at acute and chronic visits reduces subsequent receipt of preventive care. Two possible explanations for our findings for those 11–12 years for subsequent doses are: (1) providers may have vaccinated adolescents they felt were unlikely to return for well-visits, and (2) parents may have mistakenly thought vaccination substituted for a well-visit or felt a subsequent well visit was less important if their child had recently been vaccinated. Since we found that administering subsequent HPV vaccine doses at acute and chronic visits for 11–12 year olds may modestly reduce the attendance or delay the timing of subsequent well-visits, vaccination at acute or chronic visits should be accompanied by scheduling the next well-visit and emphasizing its value. Across all ages and doses, vaccinating at acute and chronic visits did not cause a statistically significant reduction or delay in well-visits, findings that may reassure clinicians. Of greater concern is the persistence of missed opportunities for HPV vaccination at acute and chronic visits that leave children at risk for HPV-related cancers.

Data came from 37 practices (18 states) which were part of a subsequent HPV vaccine intervention trial, and overall HPV vaccination rates were higher than those nationally; thus, findings might not generalize to a nationwide sample.

In our study, high rates of missed opportunities and our overall findings suggest that the benefits of capturing all vaccination opportunities likely outweigh the modest risk of potential delay or decrease in subsequent preventive care.7,9,10 

Dr Fiks conceptualized the design of the study, drafted the manuscript, and led the review and revision of the manuscript; Dr Szilagyi conceptualized the design of the study and reviewed and revised the manuscript; Ms Hannan drafted and revised the manuscript and provided administrative and technical support; Dr Humiston, Ms Breck, Ms Kelly, Dr Grundmeier, Dr Wright, Ms Albertin, Dr Shone, Ms Steffes, Dr Rand, Dr Kominski, Dr Abney, and Dr McFarland all provided substantial contributions to the conception, design, execution, and interpretation of the work, and revised the manuscript; Drs Stephens-Shields and Localio contributed to the design, performed all data analyses, contributed substantially to the interpretation of the data, and revised the manuscript; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

The overarching randomized trial was registered with ClinicalTrials.gov under NCT03599557.

FUNDING: This study was funded by the National Cancer Institute of the National Institutes of Health under Award Number R01CA202261. Additional infrastructure funding was provided by the American Academy of Pediatrics and the Health Resources and Services Administration of the US Department of Health and Human Services under UA6MC15585, National Research Network to Improve Child Health and U5DMC39344 - Pediatric Research Network Program. The information, content, and/or conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by the Health Resources and Services Administration, Department of Health and Human Services, or US Government. Funded by the National Institutes of Health (NIH).

CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no conflicts of interest to disclose.

HPV

human papillomavirus

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Supplementary data