Protocol v2.0: Changes were made to: • Align the documentation of persistent hrHPV infection inclusion criteria with clinical practice in the secondary care setting • Remove reference to focal CIN2 to align with standard of care in all countries in which the study is to be performed. Consequently, Pap smears will no longer be performed. • Update the target concentration of ChAdOx1-HPV to 8 x 1010 vp/mL as the drug product manufacture yield exceeded expectations. The delivered doses to the participants remain the same by use of a different injected volume. • Update the Investigational Medicinal Product (IMP) storage conditions to 2-8°C, as a result of recently reported stability data • Allow for sites to take only one cytobrush sample. Collection and analysis of a second sample will be performed only by those sites who can ensure delivery of a sample to the analytical laboratory within a 2-hour window from the sample being taken. • Mandate that the Investigator should notify the Sponsor within 24 hours of becoming aware of an SAE and clarify that SAEs should be reported via the SAE page of the eCRF • Ensure that colposcopy data collected is appropriate to the development of the study vaccines • Provide further clarity and correct typographical errors

In response to Medicines & Healthcare products Regulatory Agency (MHRA), UK assessment: • Clarification of the data to be reviewed by the SMC to support dose escalation between the groups has been added. • Clarification that review of the safety profile results and adverse events of the sentinel participant 72 hours after dosing in each group in the lead-in phase will be performed by the CRO Medical Monitor and a review memo will be sent to each of the sites participating in the lead-in phase to confirm that the 2nd and 3rd participant may be dosed has been added. • The dose of MVA-HPV administered to participants in Group C of the lead-in phase has been amended to 1 x 108pfu. • The study stopping/pausing rules have been updated to include two Grade 3 unsolicited adverse events occur that are considered related to study vaccine, regardless of type • The definition of post-menopausal status has been updated. • Clarification of the duration of contraception requirements has been added. In response to Federal Agency for Medicines and Health Products (FAMHP), Belgium assessment: • Clarification of the data to be reviewed by the SMC to support dose escalation between the groups and clarification that the dosing of a sentinel participant in the lead-in phase applies at both Day 0 and Day 28 has been added. • The dose of MVA-HPV administered to participants in Group C of the lead-in phase has been amended to 1 x 108pfu. • Clarification that progestogen-only hormonal contraceptives without inhibition of ovulation are not considered to be highly effective, has been added Clarification that the presence of blood dyscrasias will exclude a potential participant from the study. • The study stopping/pausing rules have been updated to include one Grade 3 adverse event considered related to the study vaccine, regardless of type, during the lead-in phase.

Changes were made to: • Update the study vaccine storage conditions to below -65°C to allow for a longer storage duration at investigator sites. Clarify the temperature record review process upon study vaccine shipment and clarify that additional study vaccine administration guidance is contained in the Pharmacy Manual. • Introduce individual participant stopping criteria to improve participant safety. • Introduce SARS-CoV-2 PCR testing at screening and prior to Day 0 and Day 28, if the participant is showing symptoms of COVID-19, or there has been known exposure, to improve participant safety. • Add an exclusion criterion of ‘Current infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as evidenced by PCR laboratory testing’ to improve participant safety. • Amend exclusion criterion 2 to align with the prednisone dose included in the list of concomitant medication to be avoided in Section 5.10

Changes were made to: • Update the Sponsor’s Authorised Representative to Margaret Marshall MD • Update the summary of clinical experience to reflect use of the ChAdOx1-vectored COVID-19 vaccine and Vaccitech access to study data • Update the study vaccine storage conditions to below -70°C to reflect current stability data. • Remove study-specific SARS-CoV-2 PCR testing to improve site staff and participant safety. Sites will follow their local SARS-CoV-2 public health guidance and procedures. • Amend inclusion criterion 4 to recognize sexual abstinence as an acceptable method of birth control only if the participant refrains from heterosexual intercourse during the entire study period and it is the usual lifestyle of the participant, in order to make it consistent with Heads of Medicines Agencies (HMA), Clinical Trials Facilitation Group (CTFG) guidance. • Amend exclusion criterion 5 to add an example of possible previous severe allergen. • Amend exclusion criterion 7 and Section 5.10 to reflect current known ChAdOx1 vaccine potential interactions. • Allow for study vaccinations to be administered within a window of ± 2 days • Reformat the study pausing/stopping rules to clarify meaning. • Add the solicited adverse event severity rating guidance provided to the participants. • Add a Belgium Co-ordinating Principal Investigator to the Safety Monitoring Committee