Phase III clinical trials of human papilloma virus (HPV) vaccination have shown !95% efficacy against HPV16/18 associated cervical intraepithelial neoplasia (CIN) Grade 2/3. Long-term surveillance is, however, needed to determine the overall vaccine efficacy (VE) against CIN3 and invasive cervical carcinoma (ICC) person years for the HPV6/11/16/18, original placebo and reference cohorts, after excluding cases discovered during the clinical follow-up and individuals not at risk. The numbers of CIN3 and ICC cases identified were 0 and 0, 3 and 0, 59 and 3 for the HPV6/11/16/18, placebo and the unvaccinated reference cohorts. The corresponding CIN3 incidence rates were 0/ 100,000 (95% confidence interval 0.0-106.5), 87.1/100,000 (95% CI 17.9-254.5) and 93.8/100,000 (95% CI 71.4-121), respectively. Long-term surveillance up to 8 years (and longer) post vaccination of the HPV6/11/16/18 vaccine and placebo cohorts, and the unvaccinated reference cohort (not exposed to interventions) for the most stringent efficacy end-points by passive cancer registry-based follow-up is feasible..Cervical cancer has an estimated worldwide incidence of 530,000 which with an incidence of 15.2/100,000 women years makes it the third most common cancer in women 1 and one of the most important causes of premature death in women. High-risk (hr) human papillomavirus (HPV) types, most notably HPV types 16 and 18 are responsible for approximately 70% of cervical cancers. 2,3 Screening programs implemented since 1960s have decreased both incidence and mortality of cervical cancer in the developed countries. As hrHPVs play a necessary role in the development of neoplastic cervical lesions, 4,5 vaccination against hrHPV infections has the potential to prevent both invasive cervical cancer (ICC) and cervical intraepithelial neoplasia (CIN). Phase III clinical trials on quadrivalent HPV6/ 11/16/18 vaccine (Gardasil TM ) have demonstrated >95% vaccine efficacy (VE) against persistent HPV16/18 infections and associated high grade cervical intraepithelial neoplasia (CIN2þ) lesions. 6,7 Even though significant overall protection against CIN2/3 has been demonstrated, a question remains about the actual effectiveness of HPV6/11/16/18 vaccination against cervical cancer, 8,9 and VE against the surrogate endpoints needs to be verified by VE data using the most stringent end-points: CIN3 and ICC that are superior to the unstable and somewhat irreproducible CIN2 end-point mostly used in the clinical trials. 10,11 Understanding the long-term protection of HPV vaccination against high-grade cervical precancer (CIN3) including carcinoma in situ or against ICC requires follow-up of the vaccinated and placebo cohorts over an extensive period of time, and comparison of the follow-up results with those of a population-based, similarly aged, randomized reference cohort