Box 2.

Recommendation for future trials to address the uncertainties.

• Vaccinate prior to onset of sexual activity and begin assessment of endpoints at age of usual cervical screening once sexually active

• Make all clinical study reports including anonymised individual patient data publicly available

• Separate trials to assess the benefit in women already exposed to HPV, without restrictions based on risk factors

• Analyse data by country and study site

• Ensure the testing interval is in line with usual cervical screening protocols

• Continue follow-up for minimum 20 years from the time of sexual debut

• Power trials for primary composite outcome CIN3/AIS/cervical cancer due to oncogenic HPV types

• Define secondary outcome of persistent infection with HPV 16/18 at a minimum of 12 months

• Use standardised testing methods for HPV detection.

• Undertake a saline placebo-controlled efficacy trial of Gardasil-9 in previously unvaccinated participants, as it is difficult to draw conclusions on efficacy and risk of harms based on the trial comparing Gardasil-9 against Gardasil.