Human papillomavirus (HPV) testing is replacing cytological screening for cervical cancer. Our aim was to assess the expected benefits and harms of different cervical screening strategies. This study is sub-analysis of a previous cost-effectiveness study with a target population of unscreened women without cervical cancer aged ≥ 25 years. A recursive decision-tree with one-year cycles was used to model the life-long natural HPV history. Markov cohort simulations were used to assess the expected outcomes from the model. The outcomes of three strategies were compared with the absence of screening: HPV-testing on self-collected vaginal samples (Self-HPV) followed by colposcopy (Self-HPV/colpo), Self-HPV and triage with cytology (Self-HPV/PAP), cytology and triage with HPV (PAP/HPV). All screening strategies resulted in reductions in cancer cases and deaths. Self-HPV strategies were associated with a lower cancer incidence and mortality life-long, not only when performed every 3 years but also when Self-HPV was performed every 5 years vs cytology every 3 years. The gain in life expectancy obtained was 82 days with Self-HPV/colpo, 81 days with Self-HPV/PAP and 75 days with PAP/HPV compared to no screening. The number of lifetime total visits was greater with PAP/HPV compared with the Self-HPV strategies (13.13 vs < 3). The number of conizations remained relatively stable with the change of screening frequency and strategy. Self-HPV may represent a reasonable balance of harms and benefits when performed every 5 years compared to cytology every 3 years. Self-HPV/PAP yielded the most efficient harm to benefit ratio when using colposcopy as a proxy for harms.