About 500,000 new cases of cervical cancer and 250,000 related Pifithrin-�� deaths are estimated to occur yearly worldwide [27]. Incidence and mortality

crude rates are 16.0 and 8.9 per 100,000 per year (age standardised rates 16.2 and 9.0, respectively) worldwide [28]. In Italy the mean incidence of cervical cancer is 9.8 cases per 100,000 women per year (nearly 3500 new cases yearly) and the adjusted mortality rate is 2.2 deaths per 100,000 women per year [28]. In Italy, in 2005, 116 organised screening programs were activated with a diffusion of 66.7% (Fig. 1). The diffusion of screening programs has increased, mainly in Central Regions, throughout the years but only 13 regions have started, in 2005, a complete screening program involving all the regional target population [29]. The adhesion find more to screening programs was nevertheless scant, under 40% [29]. A part of screening programs, the majority of women attended to regular Pap test in a private setting. According to ISTAT survey, 70.9% of women from 25 to 64 years submitted to pap test

at least one time in own life and 82.5% of them repeated pap test more than once even though only 13.7% every three years [10]. PASSI survey showed that 78.2% of women from 25 to 64 years were screened at least once in their life and 69.5% made the Pap test every three years as recommended [11]. The current strategies to treat CIN1 and CIN 2/3 in Italy are as follows: women affected by CIN1 are generally (more than

60%) followed up with yearly Pap test and colposcopy whereas those affected by CIN 2/3 are treated, and than followed up with six-monthly Pap test, colposcopy and HPV test. The total cost of a yearly follow Carnitine dehydrogenase up derived from the sum of the following costs: • Pap test: about 15 €; From the analysis of the Italian SDO database, hospitalisation mean costs related to in situ cervical cancer and invasive cervical cancer were estimated 1745.87 € and 2616.16 €, respectively. Considering national CIN prevalence, the annual cost to manage CIN could be considered between 18 and 30 million €. The cervical cancer management cost could be estimated in around 40 million €. Both quadrivalent and bivalent HPV vaccines have shown in clinical trials high efficacy against persistent HPV infections and precancerous lesions (CIN2+) together with a good safety profile. The bivalent vaccine showed in the phase III clinical trial interim analysis a cross-protection effect against oncogenic HPV genotypes, other than 16 and 18 [18] (27% efficacy on persistent infections). Studies included in the meta-analysis [30] were the following: 1. Brown et al., published on Vaccine in 2004 [31]. All the studies were clinical trials evaluating vaccine efficacy and were judged of good quality according to JADAD scale (JADAD score ≥ 3). Considering all the studies, a 10-fold decreased risk of HPV 16 persistent infection was observed in vaccinated subjects (RR: 0.10, 95%CI: 0.07–0.15) (data not shown).