Journal of Vaccine Research 2024, Vol.14, No.6, 307-315 http://medscipublisher.com/index.php/jvr 310 (Kamolratanakul and Pitisuttithum, 2021). Other side effects, like fever, headache, and feeling tired, were also reported. However, these reactions happened at similar rates for all three vaccines. 4.2 Incidence of rare and severe side effects Serious side effects after HPV vaccination are very rare. Large reviews and studies have found no strong evidence that the vaccines increase the risk of serious health problems, such as demyelinating diseases or nervous system conditions like complex regional pain syndrome or postural orthostatic tachycardia syndrome (Arbyn and Xu, 2018). A Cochrane review of clinical trials also showed that people who received HPV vaccines did not have higher rates of severe side effects or negative pregnancy outcomes compared to those who received a placebo (Ciavattini et al., 2020). Overall, the vaccines are considered very safe based on current research. 4.3 Safety studies of vaccines in special populations There isn’t much safety data on HPV vaccines for pregnant women, but the studies so far are encouraging. Research shows that the bivalent and quadrivalent vaccines don’t raise the risk of miscarriage, birth defects, or other pregnancy-related problems compared to women who didn’t get the vaccine. Still, HPV vaccines aren’t recommended during pregnancy. If someone becomes pregnant while getting the vaccine series, the remaining shots should wait until after the baby is born (Phillips et al., 2018). For people with weak immune systems-like those with HIV-there are fewer studies. But the available research shows that HPV vaccines are safe for them and still help the body build an immune response. The nonavalent vaccine, in particular, has been shown to offer strong protection against HPV in these groups. 5 Vaccination Schedule and Cost-Effectiveness Analysis of the Three HPV Vaccines 5.1 Differences in dosage and intervals between vaccinations and clinical adaptability The bivalent, quadrivalent, and nonavalent HPV vaccines each have different dosing schedules. At first, the bivalent and quadrivalent vaccines were given in three doses. But newer studies have shown that two doses can work just as well for younger people. For example, girls aged 9 to 15 had similar antibody levels whether they got two or three doses, even five years after vaccination (Phua et al., 2021). Also, giving the doses farther apart—like 6 or 12 months—can lead to stronger immune responses than shorter gaps, such as 2 or 6 months. The nonavalent vaccine, which protects against more HPV types, is also given in two doses for younger people. For older individuals or those with weaker immune systems, a three-dose schedule is still recommended. Some studies have even tested mixed schedules, like one dose of the nonavalent vaccine followed by one dose of the bivalent. These mixed approaches have shown good results, with all participants developing antibodies to all nine HPV types in the nonavalent vaccine. 5.2 Economic and cost-effectiveness comparisons of vaccines Cost-effectiveness studies have shown that two-dose HPV vaccine schedules are usually more affordable than three-dose schedules—as long as the protection lasts at least 20 years. For example, a study in the UK found that using two doses of the bivalent or quadrivalent vaccines was highly cost-effective. Adding a third dose only made sense if it provided lifetime protection (Jit et al., 2015). When comparing the bivalent and quadrivalent vaccines, the quadrivalent vaccine often turns out to be more cost-effective. This is because it also protects against anogenital warts. A study using a transmission model found the quadrivalent vaccine was more economical than the bivalent one—unless the bivalent vaccine gave longer-lasting protection and the local burden of genital warts was very low (Bergman et al., 2019). The nonavalent vaccine, which covers more HPV types, has also been shown to be cost-effective. In a study from Canada, it remained cost-effective even when assuming shorter protection time and slightly lower effectiveness than the quadrivalent vaccine. However, to stay cost-effective, the price per dose of the nonavalent vaccine needs to stay below a certain limit.
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