Overcoming barriers to HPV vaccination: non-inferiority of antibody response to human papillomavirus 16/18 vaccine in adolescents vaccinated with a two-dose vs. a three-dose schedule at 21 months.

For middle and low-income countries, the cost of HPV vaccines remains challenging. We conducted an open-label nonrandomized clinical trial evaluating immune response to the HPV-16/18 AS04-adjuvanted vaccine administered on a standard (months (M) 0-1-6) versus extended schedule (M 0-6-60) at 7, 21, 60, 72 and 120 months post-vaccination. Participants were females recruited in Morelos, Mexico: 474 girls aged 9-10 years and 500 women aged 18-24 years receiving a standard schedule, and 1026 girls aged 9-10 years receiving an extended schedule (currently the girls in the extended schedule had received only the first 2 doses). This report presents the interim analysis results for non-inferiority between the regimes conducted with the current available data at 21 months after the first dose, with serum antibodies assessed by ELISA. A pre-stated margin of non-inferiority was defined by post-vaccination geometric mean titer (GMT) ratio (upper 95% confidence interval [CI]≤2.0) between the standard and the two-dose schedule in girls at month 21. Immune response to the vaccine was strongest in adolescent girls and in the 3-dose group. Statistical non-inferiority of the two-dose versus three-dose groups was demonstrated. At 21 months, comparing the adolescent 2-dose versus 3-dose groups, the GMT ratio and 95% CI were 1.66 (1.55-1.81) and 1.67 (1.51-1.86) for HPV16 and 18, respectively. The two-dose regimen was non-inferior when compared to the three-dose response in same-age girls and with women aged 18-24 years after 21 months of follow-up. The reduction in the number of doses from the current three-dose schedule may lower overall costs associated with the vaccination and increase accessibility and compliance with the recommended dosing of the HPV vaccine.

From causality to prevention - the example of cervical cancer: my personal contribution to this fascinating history.

The history of the generation of an hypothesis linking human papillomavirus to cervical cancer, as well as a summary of the various molecular epidemiological studies undertaken to confirm such hypothesis are described.

Recommendations for cervical cancer prevention in Latin America and the Caribbean.

Cervical cancer control in the Latin America and Caribbean (LAC) region has been, and remains, a priority and a major public health challenge. It also provides the opportunity for the advancement of research into novel cervical cancer preventative tools including the use of prophylactic human papillomavirus (HPV) vaccines, HPV-based screening options and low technology visual inspection methods. The challenges for prevention are compounded because cervical cancer cases continue to cluster in the low socio-economic and rural populations, thus requiring strong political and social commitments to ensure effective implementation in the region. Although cytology-based screening activities exist in the majority of LAC countries, these have been largely based on opportunistic screening services. Evaluation of the impact of screening is often focused on assessing coverage of the population with Pap smears. However, regardless of the chosen technology a screening program requires a complex set of activities that must also be of high quality such us ensuring access of the underserved populations to the program, maintaining routine quality controls of the screening procedures and organizing the proper follow-up of women with abnormal screening results. The cost of the HPV vaccine and of the delivery infrastructure required is currently a significant obstacle for widespread introduction that will require collaborative resolve between public health organizations, governments and vaccine manufacturers. It is important to ensure that HPV vaccines are made available to the wider public, not only to those who can afford it. This monograph and the associated regional reports have carefully identified and discussed the many challenges and opportunities to be considered for policy decisions, in particular the complex interplay between vaccination strategies and subsequent screening requirements. An advanced cost-benefit analysis, using models calibrated to specific countries in the region, presents the range of options and relative costs thus providing evidence-based scientific guidance to governments and providers in the context of a significant and systematic international review effort.

Integration of human papillomavirus vaccination and cervical cancer screening in Latin America and the Caribbean.

Despite substantial efforts to control cervical cancer by screening, most Latin American and Caribbean countries continue to experience incidence rates of this disease that are much higher than those of other Western countries. The implementation of universal human papillomavirus (HPV) vaccination for young adolescent women is the best prospect for changing this situation. Even though there are financial challenges to overcome to implement such a policy, there is broad political support in the region for adopting universal HPV vaccination. The costs of implementing this policy could be largely alleviated by changing cervical cancer control practices that rely on inefficient use of resources presently allocated to cytology screening. In view of the strong evidence base concerning cervical cancer prevention technologies in the region and the expected impact of vaccination on the performance of cytology, we propose a reformulation of cervical cancer screening policies to be based on HPV testing using validated methods followed by cytologic triage. This approach would serve as the central component of a system that plays the dual role of providing screening and surveillance as integrated and complementary activities sharing centralized resources and coordination.