Elimination of cervical cancer from Europe
Dr. Xavier Bosch presented the core concept and an estimate of the impact of the HPV-FASTER strategy [1]. Putting HPV vaccination of adult women (up to 45 years of age) in perspective, Dr. Bosch noted that the reported efficacy of the prophylactic HPV vaccines against cervical HPV infection and associated diseases has ranged between 85% and 100% in adult women provided they are HPV negative at the time of vaccination.
Between 2006 and 2016 the target populations for vaccination have expanded to include both genders in several developed countries and several catch-up cohorts in many countries. However, in spite of 10 years since vaccine introduction, the coverage of HPV vaccination of adolescent girls in the developing parts of the world remains low to anecdotal.
Vaccination of adult women in the public program extended to age 26 in Australia, and the European licensing expands from age 9 onwards without any upper age limit. Further, the composition of one of the currently available vaccines includes and provides protection against 9 HPV types (7 high-risk types and 2 low-risk types), and two-dose vaccination is now considered sufficient for individuals below the age of 15 years of age provided that the second dose is delivered 6-12 months apart. The two-dose indication extends, to date, to girls or boys below the age of 15 that are immunocompetent. However, two-dose trials are under way in middle aged women and even one–dose trials have been initiated in order to fully explore the protection power of these vaccines. Public programs also benefit from negotiated prices of the vaccine. Therefore, the costs of the vaccination programs are reduced as compared to the 2006 indications. In countries with extensive vaccination coverage, screening programs have accelerated their transition from cytology-based to HPV-based testing as their primary option and ongoing studies are trying to define their optimal protocols for age at screening initiation, frequency and interval duration between screening rounds and the adequate triage options for HPV positive women in the different settings and human development strata.
The master concept of the HPV-FASTER project claims that a woman in the middle age groups that is found HPV-negative and has received a broad spectrum HPV vaccine, has a subsequent very low risk of cervical cancer. Under these very low risk estimates, the requirements of further HPV screening are likely to be minimal and necessarily HPV based. The bare minimum of an HPV-FASTER strategy proposes that vaccination expands to middle aged women (ages to be determined in the 40 to 45 range) and is paired with at least one HPV screening and treatment episode in the ages 30 to 35.
Figure 1 shows, in a schematic way, the HPV-FASTER strategy and the expected impact in disease reduction. HPV vaccination is offered to women from 9 to 30 years of age in a routine program, expecting a 90+% protection among HPV- negative women. Between ages 30 and 45+ the percentage of HPV-positive women is between 5 to 10% and these women will be also offered vaccination paired with one HPV testing episode. Using current technology, only a marginal proportion (less than 5%) of the HPV-positive women will be missed by a validated HPV DNA/mRNA test. The screen-detected HPV-positive women will enter a triage and follow-up protocol until HPV clearance or if a CIN2+ lesion is identified into pertinent treatment and follow-up. In developing populations, screen and treat protocols need to be evaluated.
This algorithm is expected to provide at least 60% protection against invasive cervical disease with two/three lifetime visits, which is one of the anticipated requirements for sustainability of preventive programs in most underdeveloped areas of the world. The net impact of the FASTER strategy is to accelerate the protection gained from available interventions – probably not only against cervical cancer but also against all other HPV-associated cancers. An HPV- FASTER feasibility project is ongoing under the FP-7 CoheaHR network to test the logistical, acceptance/compliance, and safety issues of the strategy in European countries. Similar projects are underway in Mexico and Australia.
Figure 1. The HPV-FASTER core concept and expected impact. The proposal of the HPV-FASTER is to offer HPV vaccination to women in a broad age range of 9 to up to 45 years, paired with at least one HPV screening test at any age at or above 30 years. Vaccination will be offered irrespective of HPV-infection status. HPV screening needs to be complemented with a triage/diagnostic assessment among women who screen HPV positive and treatment of the pre-neoplastic cases is mandatory. Screen-and-treat protocols can be considered in some populations. Modified from [1].