Phase2 trial (ph2,1v).

Methods	Phase IIb, randomised, double‐blind, placebo‐controlled trial
Participants	2392 women (1194 in the vaccine arm and 1198 in the placebo arm) from 16 centres in the USA Age range: 16 to 23 years Inclusion criteria: young women who were HPV16 DNA negative at enrolment and month 7, were HPV16 seronegative at enrolment, had had no other vaccination ±1 month around each dose. Virgins were enrolled if they were seeking contraception Exclusion criteria: pregnancy, history of abnormal Pap smears, more than 5 sexual partners
Interventions	Vaccine: monovalent HPV16 L1 virus‐like particles Placebo: visually indistinguishable aluminium adjuvant placebo
Outcomes	Safety, immunogenicity and efficacy (persistent HPV16 infection and histological lesions of CIN 1+,2+ and 3+)
Notes	Reports: Koutsky 2002; Mao 2006 and Rowhani‐Rahbar 2009 Last report average follow‐up time: 8.5 years (Rowhani‐Rahbar 2009)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Study participants were randomised in a 1:1 ratio to receive vaccine or placebo. Permuted blocks were used to ensure similar numbers of participants in each arm
Allocation concealment (selection bias)	Low risk	Allocation sequence was generated by computer, allocation numbers were assigned at each centre. No further details were provided regarding the concealment of allocation
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants and study staff were blinded to the group assignments
Blinding of outcome assessment (detection bias) All outcomes	Low risk	An independent masked group of 4 pathologists reviewed the slides without knowledge of other clinical or laboratory data
Incomplete outcome data (attrition bias) All outcomes	Low risk	Besides the per‐protocol (PP) analysis (HPV16 DNA negative at enrolment and during vaccination, HPV16 seronegative at enrolment, 3 doses received, no protocol violations) also modified‐intention‐to‐treat (MITT‐1 [HPV16 DNA negative and seronegative at enrolment, at least 1 dose received], MITT‐2 (including also women being HPV16 DNA positive at enrolment) analyses were performed. Unrestricted susceptible population and ITT analysis done. Exclusions and reasons for exclusions were described and were balanced over the trial arms.
Selective reporting (reporting bias)	Low risk	All outcomes (safety, immunogenicity and efficacy) were presented