[MUSIC] I'm going to start with some epidemiology data about cervical cancer. Cervical cancer is the fourth cancer among women. We had 530,000 new cases of cervical cancer worldwide in 2012, and it represents 13% of all cancer among women. And it represents also the fourth cause of death among women. Most, the great majority of cases and deaths occur in developing countries. In fact, 87% of deaths have been in developing countries in 2012. The Papanicolaou test had been introduced firstly in 1941. And it's consisting in a test where you take some material during gynecological visit, and then you put on a slide and read with the microscope and look for some morphological changes in the cells. Very soon it became the main test we use to detect cervical cancer, pre-invasive cancer lesions, and then being used in many countries as a screening test. And since, starting already during the late 50s, early 60s, we could started to see an amazing decrease of incidents of mortality for cervical cancer in all all the cancers that implemented such screening programs. So although there had never been the formal randomized trials that evaluated the effectiveness and efficacy of the PAP test as a screening test, there are no doubts that it is, thanks to this test, that we have served such a degree in most countries. We had also some new findings lately about cervical cancer and the beginning of the 90s, we finally, without any doubt, linked the permanent infection with the Human Papilloma Virus, HPV virus in the development of cervical cancer. In fact, in 1994, the International Agency of Research for Cancer declared at least 12 types of HPV viruses as carcinogenic. And two of them, the HPV 16 and HPV 18, are considered responsible for at least 70% of all cervical cancer worldwide. And after that, around 2006 and 2007, there were two vaccines, HPV vaccines, that have been released and a lot of countries started some immunization programs, worldwide. At least 52 countries in 2015 had implemented such programs. 41% in high and 15% in low or medium income countries. So we have a lot of tools that we can use to reduce the burden of this disease n using vaccination as a primary prevention tools or screening test as a secondary prevention tools. So the vaccination of pre-adolescent and adolescent girls has been proven effective against the lesions that the HPV virus causes. Of course, we don't have still the long term results on cervical cancer because of the longer natural history of this cancer. We have to wait at least 20, 25 years before that. Then we have the Pap test with sensitivities around 53% and specificity 96% for lesions like cervical intraepithelial lesions 2 and plus, we saw already had a big effect in reducing incidents and mortality for this cancer. The problem with the test though is that in its high quality and collection phase, it's a quite repetitive test and so it can lead to a lot of errors during the interpretation of the slides and is also highly subjective. So as we have seen in other tests, the HPV DNA test has an actually a much higher sensitivity of between 20-45% higher than for the PAP test to detect seeing 2 plus lesions, although the specificities is a little bit lower. And this test has been proven also to be more effective to reduce the incidence of the cervical cancer for five years after one test in life and to reduce mortality after 80 years. And then we have also another possibility, which is the VIA, which is the Visual Inspection with Acetic Acid, which is being used mostly in less developed regions, particularly India and Uganda. Again, successful programs with the VIA, and the so called see and treat strategy which, it's very useful on those regions where the access to clinics is difficult and the follow up of women is also difficult. So once the woman is seen in the clinic and is found positive the VIA, she's being treated. So we have several strategies, and then it depends really on one thing. It depends on the burden of disease, and it depends on the resources of the country to choose which one to choose. And in situation where the universal vaccination is deferred for a long time, it's obviously the case to keep the screening program which is in place, the PAP test screening program, and not change it. And this is probably the case in most developed countries, while in developing countries this is probably not possible, so other strategies using the VIA or HPV test should be chosen. Also because they need a less frequent test, and the the intervals between the tests are much larger. Even in situation in those countries, though, where a universal vaccination against HPV infection is implemented, we still need to keep these screening programs to screen the women that have never been vaccinated because they are too old, they are not in the target age for screening. And to screen also the women that been vaccinated, because they been vaccinated only against two types of HPV virus, so they can still get infected with the other ones. So once again, depending on the level of the resources, it can be chosen to keep the PAP test program, whatever it is, already in place or to use the other strategies according to the capacity. So to conclude, we have a very important public health problem, very important particularly, in less developed countries. But we have a lot of tools. We have one tool that can let the primary prevention, which is the vaccination, the universal vaccination. And then we have some screening tests, Pap test, HPV test, VIA, that can be used, that need to be used for, in both cases either with the vaccination or without the vaccination. And the choice of all these strategies depends on the burden of disease and the availability of resources. [MUSIC]