Starting from May 1, 2017 in Australia the National Cervical Screening Program will shift from cervical cytology every two years, to HPV DNA testing as the sole primary screening test every five years in women aged 25 to 74 years, together with the implementation of an active HPV vaccination program [1]. Conversely in Japan cervical screening using cytology every two years is still being recommended for population-based and opportunistic screening [2]. While Canadian guidelines also recommend cervical screening with cytology every 3 years [3], in Europe cervical cytology is recommended for women under 30-35 years, and HPV testing as the sole primary screening test every 5-10 years for women above 30-35 years [4]. Actually, guidelines do not represent the real situation in each European country. In the Netherlands, screening is well organised and relies on primary HPV testing every 5 years until 40 years of age and every 10 years for women aged 40 and beyond: no screening is provided for women under 30, nor over 60 years of age [5]. Other countries recommend cytology or HPV testing, and differences are marked even within the same country and sometimes within the same region. As a matter of fact in Italy there are regions employing cytology, other regions employing HPV DNA testing, and one local health unit employing HPV mRNA testing as the sole test, while some regions still do not implement organized screening programs [6]. In the U.S. guidelines for cervical cancer screening are well-structured and - in their effort to reach maximum cost-effectiveness - are articulated into several scenarios. Briefly, cytology alone every 3 years is recommended for women under 30 years, while women aged 30 to 65 years may either continue screening with cervical cytology every 3 years, or offered cotesting(cytology + HPV testing) if they want to be screened less frequently [7-9]. Interestingly, European guidelines insist that only one primary test (either cytology or HPV testing) should be used at any given age in cervical cancer screening. In the U.S. until more data and algorithm development will be available, it is judged premature to use HPV testing alone as a valid screening approach [10]. This is the reason why the latest edition of the CDC guidelines published in June 2015 state that HPV testing should not be performed in screening for cervical cancer as a stand-alone test (i.e., without a concurrent Pap test) [11].