Timing and deaths averted with one-time prevention campaigns: vaccination only, screening only, or both

Footnote Figure 1: Projection of the relative timing of health benefits, measured as deaths averted, accrued by vaccination and/or screening applied through one-time campaigns. Three scenarios were examined: 1) a one-time screening campaign providing effective management for approximately 25% of 30-to 49-year-old women in 2027 (i.e., 20 birth cohorts) (green line); 2) vaccinating 90% of 9-to 14-year-old girls in 2027 (i.e., 6 birth cohorts) with a bivalent HPV16/18 vaccination (orange line); and 3) both a screening campaign and HPV vaccination for respective birth cohorts in 2027 (blue line). We considered cervical cancer deaths averted over the lifetime of cohorts subject to the intervention, and conservatively assumed that deaths averted due to screening would only occur after age 50, to account for prevalent cancers. Projections were developed for the ∼65 LMIC with age-standardized cervical cancer incidence greater than 10 per 100,000 women.8 Even a relatively short-term intervention that combines screening and vaccination could avert over 1.2 million deaths over the lifetime of intervention cohorts, and implementation of effective screening campaigns could lead to reductions in cancer mortality almost immediately.

Risk-based PAVE screen-triage-treat strategy provides risk stratification to assist in the management of screening participants.

Note: hrHPV: refers to those HPV types considered as having a high potential capacity to induce cervical cancer when the infection is persistent over time. It includes HPV 16,18,45,31,33,45,52,58,39,51,56,59 and 68

Map of PAVE study sites

Schematic of PAVE protocol elements

Theoretical approach to compare the HPV AVE strategy and the standard of care (SOC) screening and triage outcome

Footnote: Figure 5 is a hypothetical example showing how PAVE and SOC will be compared. Under a specific specificity value (which will be determined by the SOC), we will compare the difference between the sensitivities of PAVE and SOC. In this example, we had three categories for HPV genotype groups and three categories for AVE (normal-indeterminate-precancer/cancer), and in total nine PAVE categories.

Site-specific primary triage and treatment protocols Biopsy and Treatment Protocols

Note: Prior to the PAVE study, El Salvador screened with primary HPV screening (clinician-collected CareHPV), Brazil and DR screened with cytology, and Cambodia, Eswatini, Honduras, Malawi, Nigeria, and Tanzania screened with VIA. All sites are introducing self-sampled HPV testing with ScreenFire as part of the PAVE protocol. In El Salvador, women are continuing to screen initially with both ScreenFire and CareHPV. Triage testing is performed in all women with HPV-positive results. In El Salvador, triage testing is also performed on 5% of those testing HPV negative.

HPV-AVE risk strata

The PAVE protocol will be compared to SOC VIA or colposcopy screen-triage protocols using the visual impressions recorded during the study. In SOC scenarios, participants are classified as positive or negative in the HPV test and as normal or abnormal in visual evaluations (e.g., VIA negative or positive, colposcopic impression less than high-grade or high-grade+) (Table 3).

Risk strata for participants with an HPV positive women and visual Standard of Care (SOC) as the triage (i.e. VIA, colposcopy) test

Note: Participants with a negative test for HPV will not have a VIA nor colposcopy assessment. see Table 1 for SOC at individual PAVE sites.