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Adjuvant Human Papillomavirus Vaccination for Patients Undergoing Treatment for Cervical Intraepithelial Neoplasia 2+

  • Practice Advisory PA
  • July 2023

This Practice Advisory was developed by the American College of Obstetricians and Gynecologists with the assistance of Lee-may Chen, MD, and Amy J. Park, MD.

This Practice Advisory serves as an update to Committee Opinion No. 809, Human Papillomavirus Vaccination, originally published in 2020 1 .


Background

The human papillomavirus (HPV)—associated with the development of cervical dysplasia and cancer, in addition to anal, vulvar, and vaginal dysplasias and cancers, genital warts, and oropharyngeal cancer—continues to be a significant cause of preventable morbidity and mortality. Even after surgical treatment, recurrence rates for cervical intraepithelial neoplasia grade 2 or 3 (CIN 2+) range from 10% to 14% 2 . Recent data from meta-analyses and observational studies demonstrate that adjuvant HPV vaccination in the setting of surgically-managed CIN 2+ in previously unvaccinated individuals reduces the recurrence of cervical dysplasia 3 4 5 6 . A meta-analysis of 11 studies (n=21,310) that compared adjuvant HPV vaccination with surgery alone reported a 65% overall risk reduction of new or persistent CIN 2+ with adjuvant HPV vaccination 3 . Another systematic review and meta-analysis of 22 papers also found evidence on the benefit of adjuvant HPV vaccination, especially for CIN 2+ related to HPV genotypes 16 or 18 4 . Additionally, according to a decision analysis published in 2023, adjuvant HPV vaccination for CIN 2+ results in improved quality of life and cost savings due to fewer recurrences of CIN, Pap tests, colposcopies, and repeat excisional procedures 7 . Data from randomized controlled trials are expected to be published in the future.

For individuals who are immunocompromised, the role of “catch-up” vaccination is less clear because of concerns about the effectiveness of HPV vaccination to reduce subsequent CIN 2+ in patients with human immunodeficiency virus, a history of solid organ transplantation, or those taking recently prescribed immunosuppressive medications 8 . More data are needed for these populations.

Updated ACOG Recommendation

Based on data on the benefit of adjunct HPV vaccination, ACOG recommends adherence to the current Centers for Disease Control and Prevention (CDC) recommendations for vaccinations of individuals aged 9–26 years, and to consider adjuvant HPV vaccination for immunocompetent previously unvaccinated people aged 27–45 years who are undergoing treatment for CIN 2+. This recommendation is in alignment with guidance developed by the American Society for Colposcopy and Cervical Pathology 9 . (For details on ACOG’s recommendation on shared clinical decision making for individuals aged 27–45 years who are previously unvaccinated and are not undergoing treatment for CIN 2+, see ACOG Committee Opinion No. 809, Human Papillomavirus Vaccination 1 ).

Implementation Considerations

Clinicians should consider stocking the HPV vaccine in the office in order to increase access to vaccination. If in-office vaccination is not feasible, then a compilation of resources (eg, the local health department) can aid the patient in obtaining the vaccine. Currently, the only HPV vaccine available in the United States is the nine-valent vaccine with the following schedule and dosing 10 :

  • For those younger than age 15 years: two doses spaced 6–12 months apart
  • For those age 15 years and older: a three-dose schedule with the initial dose followed by the second dose at 1–2 months, and third dose at 6 months after the initial dose

There are some data to suggest that initiating vaccination 0–3 months prior to conization rather than 0–12 months post-conization is more effective in reducing persistent or recurrent high-grade cervical intraepithelial lesions (0.9% vs 6.5%; P=.047) 11 . However, at this time, the optimal timing of adjuvant HPV vaccination remains unknown. Large randomized controlled trials that will inform future practice recommendations are ongoing.

Additional Resources

These materials are for information purposes only and are not meant to be comprehensive. Referral to these resources does not imply ACOG’s endorsement of the organization, the organization’s website, or the content of the resource. The resources may change without notice.

Please contact [email protected] with any questions.


References

  1. Human papillomavirus vaccination. ACOG Committee Opinion No. 809. American College of Obstetricians and Gynecologists. Obstet Gynecol 2020;136:e15-21. doi: 10.1097/AOG.0000000000004000
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  2. Kocken M, Helmerhorst TJ, Berkhof J, Louwers JA, Nobbenhuis MA, Bais AG, et al. Risk of recurrent high-grade cervical intraepithelial neoplasia after successful treatment: a long-term multi-cohort study. Lancet Oncol 2011;12:441-50. doi: 10.1016/S1470-2045(11)70078-X
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  3. Di Donato V, Caruso G, Petrillo M, Kontopantelis E, Palaia I, Perniola G, et al. Adjuvant HPV vaccination to prevent recurrent cervical dysplasia after surgical treatment: a meta-analysis. Vaccines (Basel) 2021;9:410. doi: 10.3390/vaccines9050410
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  4. Kechagias KS, Kalliala I, Bowden SJ, Athanasiou A, Paraskevaidi M, Paraskevaidis E, et al. Role of human papillomavirus (HPV) vaccination on HPV infection and recurrence of HPV related disease after local surgical treatment: systematic review and meta-analysis. BMJ 2022;378:e070135. doi: 10.1136/bmj-2022-070135
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  5. Karimi-Zarchi M, Allahqoli L, Nehmati A, Kashi AM, Taghipour-Zahir S, Alkatout I. Can the prophylactic quadrivalent HPV vaccine be used as a therapeutic agent in women with CIN? A randomized trial. BMC Public Health 2020;20:274. doi: 10.1186/s12889-020-8371-z
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  6. Lichter K, Krause D, Xu J, Tsai SH, Hage C, Weston E, et al. Adjuvant human papillomavirus vaccine to reduce recurrent cervical dysplasia in unvaccinated women: a systematic review and meta-analysis [published erratum appears in Obstet Gynecol 2020;135:1489]. Obstet Gynecol 2020;135:1070-83. doi: 10.1097/AOG.0000000000003833
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  7. Chaiken SR, Bruegl AS, Caughey AB, Emerson J, Munro EG. Adjuvant human papillomavirus vaccination after excisional procedure for cervical intraepithelial neoplasia: a cost-effectiveness analysis. Obstet Gynecol 2023;141:756-63. doi: 10.1097/AOG.0000000000005106
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  8. Silverberg MJ, Leyden WA, Lam JO, Chao CR, Gregorich SE, Huchko MJ, et al. Effectiveness of 'catch-up' human papillomavirus vaccination to prevent cervical neoplasia in immunosuppressed and non-immunosuppressed women. Vaccine 2020;38:4520-3. doi: 10.1016/j.vaccine.2020.05.004
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  9. Sharpless KE, Marcus JZ, Kuroki LM, Wiser AL, Flowers L. Adjuvant human papillomavirus vaccine for patients undergoing treatment for cervical intraepithelial neoplasia. ASCCP Committee Opinion. J Low Genit Tract Dis 2023;27:93-6. doi: 10.1097/LGT.0000000000000703
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  10. Centers of Disease Control and Prevention. HPV vaccine schedule and dosing. Accessed May 15, 2023. Available at: https://www.cdc.gov/hpv/hcp/schedules-recommendations.html
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  11. Henere C, Torné A, Llupià A, Aldea M, Martí C, Glickman A, et al. HPV vaccination in women with cervical intraepithelial neoplasia undergoing excisional treatment: insights into unsolved questions. Vaccines (Basel) 2022;10:887. doi: 10.3390/vaccines10060887
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The American College of Obstetricians and Gynecologists recognizes and supports the gender diversity of all patients who seek obstetric and gynecologic care. In original portions of this document, authors seek to use gender-inclusive language or gender-neutral language. When describing research findings, this document uses gender terminology reported by investigators. To review ACOG’s policy on inclusive language, see https://www.acog.org/clinical-information/policy-and-position-statements/statements-of-policy/2022/inclusive-language.


A Practice Advisory is a brief, focused statement issued to communicate a change in ACOG guidance or information on an emergent clinical issue (eg, clinical study, scientific report, draft regulation). A Practice Advisory constitutes ACOG clinical guidance and is issued only online for Fellows but may also be used by patients and the media. Practice Advisories are reviewed periodically for reaffirmation, revision, withdrawal or incorporation into other ACOG guidelines. This information is designed as an educational resource to aid clinicians in providing obstetric and gynecologic care, and use of this information is voluntary. This information should not be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. It is not intended to substitute for the independent professional judgment of the treating clinician. Variations in practice may be warranted when, in the reasonable judgment of the treating clinician, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology. The American College of Obstetricians and Gynecologists reviews its publications regularly; however, its publications may not reflect the most recent evidence. Any updates to this document can be found on www.acog.org/clinical.

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