Supplementary Digital Content 2. Study design.

Enrolled and Randomized

Injection 1 Injection 2 Injection 3

Vaccination phase completed Study completed

N=2499

n=992 n=930 n=871 Group 1

Bivalent rLP2086 + HPV4 n=999

n=864

n=848

n=990 n=924 n=869 Group 2

Bivalent rLP2086 + saline n=998

n=860

n=841

n=501 n=476 n=452 Group 3 Saline + HPV4

n=502

n=448

n=438

Reasons for withdrawal:

-No longer willing to participate, n=14 -Lost to follow-up, n=14 -No longer eligible, n=10 -Protocol violation, n=7 -Adverse event, n=3 -Other, n=5

Reasons for withdrawal:

-No longer willing to participate, n=56 -Lost to follow-up, n=29 -No longer eligible, n=13 -Protocol violation, n=10 -Adverse event, n=9 -Other, n=12

Reasons for withdrawal:

-No longer willing to participate, n=47 -Lost to follow-up, n=32 -No longer eligible, n=18 -Protocol violation, n=9 -Adverse event, n=11 -Other, n=13

Supplementary Digital Content 2. Study design.

Patients lost to follow-up were subjects who could no longer be contacted by telephone after multiple attempts and who did not respond to certified letters sent by the site.

HPV4=quadrivalent human papillomavirus vaccine.