Nearly 20 years after HPV vaccines were introduced, fewer than one in three eligible adolescent girls worldwide has ever been vaccinated. The barrier isn’t the science — it’s supply, access, and multi-dose schedules. If a single shot delivers the same protection as two, the public health implications are enormous.The ESCUDDO trial (Kreimer et al., NEJM 2025) enrolled over 20,000 girls across Costa Rica, randomized them to one or two doses of either the bivalent or nonavalent HPV vaccine, and followed them for five years. One dose was noninferior to two doses for both vaccines, with greater than 97% effectiveness against persistent HPV 16/18 infection. In this episode, I walk through the design, the noninferiority results, the nuances worth knowing, and — as always — why it didn’t score a perfect 10.━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━📊 KEY FINDINGS→ 1 dose noninferior to 2 doses for both bivalent (Cervarix) and nonavalent (Gardasil 9) → Vaccine effectiveness ≥97% against persistent HPV 16/18 in all four groups — effectively identical across one- and two-dose arms→ Rate difference (nonavalent): +0.21 infections/100 (95% CI −0.09 to 0.51) — upper bound well inside the 1.25/100 noninferiority margin→ Bivalent cross-protection against HPV 31: 38% with 1 dose vs. 83% with 2 doses — secondary finding, doesn’t change the headline, but clinically worth knowing→ Safety: 7 serious adverse events possibly related to vaccination out of 20,330 participants — no pattern, no signal📊 Castelli Coefficient: 8/10━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━🔗 LINKS & RESOURCESFull paper (NEJM): https://doi.org/10.1056/NEJMoa2506765ClinicalTrials.gov: NCT03180034Full citation: Kreimer AR, Porras C, Liu D, et al. Noninferiority of One HPV Vaccine Dose to Two Doses. N Engl J Med. 2025;393:2421-33. DOI: 10.1056/NEJMoa2506765━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━⚕️ ABOUT DISPENSE AS WRITTENEvidence-based medicine without the fluff. Every video ends with the Castelli Coefficient — a verdict that incorporates study design, statistical validity, and clinical applicability. No pharmaceutical sponsorships. No conflicts of interest. Just the data.Gregory Castelli, PharmD, FCCP, BCPS, BC-ADM, CDCESAssociate Professor | Evidence-Based Medicine EducatorYouTube: @dispenseaswrittenInstagram / TikTok: @gregcastellipharmdX / Twitter: @gregcastellirxEmail: dispensingevidence@gmail.com━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━⚠️ LEGAL DISCLAIMERThe content provided in this video is for educational and informational purposes only. It is intended for healthcare professionals and medical students as a supplement to — not a substitute for — clinical judgment, professional training, and the individualized care of patients.Nothing in this video constitutes medical advice, and it should not be used as the basis for any clinical decision regarding an individual patient. Always consult current clinical guidelines, institutional protocols, and your own clinical judgment when making treatment decisions.Gregory Castelli, PharmD, is speaking in his personal capacity as an educator. The views expressed do not represent the official positions of any institution or affiliated organization.This channel has no affiliation with, and has received no funding or compensation from, any pharmaceutical manufacturer, device company, insurance company, or other commercial entity with a financial interest in the content discussed.Use of trade names is for identification purposes only and does not constitute endorsement.━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━#DispenseAsWritten #EvidenceBasedMedicine #EBM #MedEd #PrimaryCare #FamilyMedicine #InternalMedicine #PharmD