Viral dynamics could also be affected if the duration of infectivity is affected, i.e. if prior infection with one HPV type would affect the time it takes to clear infection with another HPV type. In a population-based cohort study of >6000 women, baseline HPV seropositivity did Saracatinib clinical trial not affect the clearance rate of other HPV types [82]. Thus, it seems that the first prerequisite for type replacement – natural competition – does not apply and that type replacement is therefore unlikely. However, it should be pointed out that most

of the studies that have investigated viral type competition effects on incidence and/or clearance have had limited statistical power to detect small effects, particularly for rare HPV types. Viral escape mutants.  Apart from the risk of changes in population dynamics of already existing types, it is possible that viral mutations could

occur to generate new variants that are equally oncogenic but not recognized by vaccine-induced antibodies. However, the fact that HPV replicates using the cellular DNA polymerases and thus has a very slow mutation rate suggests that this risk is low. This is also indicated by the fact that viral variants of HPV16 from all over the world are neutralized by the same Ibrutinib manufacturer HPV monoclonal antibodies [83]. Attributable proportion/number of healthy women at risk. Because vaccination with HPV16/18 will prevent many women from dying of cervical cancer, there will be more women who

will be at risk for cervical cancer caused by other HPV types. The proportion of cases prevented if an HPV type is eliminated is therefore not exactly the same as also the proportion of positive cases, but is given by S*(1-1/RR), where S is the proportion of positive cases and RR is the relative risk. When HPV-related relative risks for cancer are increased about 100-fold, this effect is so small that it is usually ignored. However, for specific rare ‘oncogenic’ HPV types, the relative risks are not so high when compared to a reference category of all women without that specific HPV type. However, regarding the impact on HPV16/18 vaccination on cervical intraepithelial lesions, in particular low-grade lesions, RR is substantially lower, as they are caused proportionally more by other types. Therefore, HPV vaccination will have a smaller impact on low-grade abnormalities than the prevalence of HPV16/18 in these lesions [84,85]. Consideration of attributable proportions is therefore of particular relevance when discussing benefits and caveats of including additional HPV types in second-generation HPV vaccines. Monitoring of HPV vaccination programmes.  HPV differs from most other vaccine-preventable diseases in that the major diseases to be prevented occur many decades after infection.