HPV Vaccination After Cervical Conization

In human papillomavirus (HPV) vaccine–naive patients undergoing cervical conization (cone biopsy) for cervical intraepithelial neoplasia (CIN), does HPV vaccination administered shortly before or after the procedure reduce recurrent high-grade cervical dysplasia compared with no HPV vaccination?

HPV vaccination administered to HPV vaccine–naive patients around the time of conization may reduce recurrent CIN grade 2 or higher (CIN 2+) at 24 to 36 months compared with no vaccination.¹ It is unclear whether HPV vaccination at the time of conization prevents CIN 3+ or whether invasive cervical cancer is reduced. Vaccine-related harms were incompletely reported, but those harms reported appeared to be mostly mild. (Strength of Recommendation: B, inconsistent or limited-quality patient-oriented evidence.)

Cervical cancer remains a major global health concern and is the fifth most commonly diagnosed cancer in women globally.² The American Cancer Society estimated there would be approximately 13,490 new cases of invasive cervical cancer and approximately 4,200 deaths from cervical cancer in 2026 in the United States.³

CIN, a precancerous condition typically caused by persistent infection with oncogenic HPV types, is treated to prevent progression to invasive cervical cancer, most often with excisional biopsy (eg, conization). After excisional treatment, patients remain at risk of recurrent CIN or invasive cervical cancer and require ongoing surveillance.

Primary prevention of cervical cancer is most commonly achieved via HPV vaccination before HPV exposure. Population-level evidence shows that HPV vaccination reduces cervical cancer incidence by approximately 80% when given at or before age 16 years, while also reducing high-grade cervical precancerous lesions (eg, CIN 2 or 3).⁴ Although prophylactic vaccination is highly effective for primary prevention, its role as an adjuvant strategy in HPV vaccine–naive patients around the time of conization for CIN 2 or 3 is uncertain.

This Cochrane review included 13 studies (two randomized controlled trials and 11 nonrandomized studies) including 21,453 HPV vaccine–naive patients undergoing conization for CIN.¹ Studies were conducted in Europe (10 studies), China, South Korea, and Iran; none were conducted in the United States.¹ HPV vaccines included bivalent, quadrivalent, and nonavalent formulations; comparator groups received no HPV vaccination.¹ Follow-up was up to 36 months in randomized trials and beyond 60 months in some nonrandomized studies. Follow-up settings (ie, primary care or specialty clinics) were not consistently reported.

Across the two randomized controlled trials (n = 420 participants), recurrent CIN 2+ at 24 to 36 months occurred in 233 per 1,000 patients who did not receive HPV vaccination and 93 per 1,000 patients who did receive vaccination (relative risk =0.40; low-certainty evidence; absolute risk reduction = 140 per 1,000 [14%]; number needed to treat = 8).1 Evidence from nonrandomized studies showed a similar direction of effect, and the review notes that direction of effect for CIN 2+ was generally consistent despite heterogeneity in effect size. However, evidence for CIN 3+ recurrence, persistent HPV infection, and invasive cervical cancer remains very uncertain, with inconsistent findings across nonrandomized studies.

Subgroup analyses identified no differences among vaccine types. Vaccine timing and dosing varied across studies (six studies reported that at least 68% of vaccinated participants received three doses, and several studies did not report on dosing completion). Optimal timing remains uncertain. The review authors could not conduct timing-based subgroup analyses, but one large nonrandomized study (n = 17,128) showed a lower recurrence risk among patients vaccinated before conization (within 3 months), whereas patients vaccinated after conization (up to 12 months) had a similar risk to unvaccinated patients.