HPV Vaccination. Dr. Vivien Tsu PATH. HPV Vaccination 1

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1 HPV Vaccination Dr. Vivien Tsu PATH HPV Vaccination 1

2 HPV vaccine overview 1 First vaccines to focus on a female cancer. Prepared from virus-like particles (VLPs). VLPs are non-infectious. Two vaccines currently available (Merck & Co., Inc. and GlaxoSmithKline products). Current HPV vaccines are designed to protect against HPV-16 and -18; one also protects against low-risk types -6 and -11 The advent of HPV vaccines provides an unprecedented opportunity for the prevention of cervical cancer, especially in countries where screening has not provided the benefit that it has in wealthier countries. These are the first vaccines to focus on a woman s cancer. The HPV vaccines are prepared from virus-like particles (VLPs) that use recombinant DNA technology. They don t contain the full DNA, so there s no way for them to be infectious. Two vaccines are currently available from Merck and from GlaxoSmithKline. These vaccines are designed to protect against the two most important HPV types 16 and 18 that cause more than 70 percent of cervical cancers. One vaccine also includes low-risk types 6 and 11, which are unlikely to cause cancer, but do cause 90 percent of genital warts. HPV Vaccination 2

3 HPV vaccine overview 2 Both vaccines require three doses over six months. Both provide protection for at least five years, likely much longer. Both are expensive in the private market, but prices will decrease when international agencies negotiate publicsector terms. Both vaccines require three doses over a six-month period. We have good, strong evidence that they protect for at least five years, but it seems very likely that they will protect much longer than that. Both are expensive in the private market and in wealthy countries right now, but we expect those prices to decrease rapidly when negotiations for public-sector prices are done. Both manufacturers have indicated that they are willing to tier their prices so that low-income countries can benefit. HPV Vaccination 3

4 HPV vaccine: safe and effective Both vaccines are very safe: Well-tolerated with minor local side effects (soreness), some fainting. No serious adverse events seen in clinical trials or post-marketing. Efficacy >90% in women not previously infected with HPV type 16 or 18. Efficacy is much lower in sexually experienced women. Best to vaccinate prior to sexual debut (young adolescents). Preliminary evidence suggests that both vaccines provide cross-protection against additional cancer-causing HPV types. Both vaccines have proven very safe, both in the clinical trials, and in the postmarketing surveillance of the more than 20 million doses that have been delivered so far. They re well tolerated, with just minor side effects sore arm and redness and a few girls have also reported feeling light-headed or have fainted. There have been no serious adverse events in any of the trials that we ve seen so far. The efficacy the protective ability of these vaccines against cervical lesions has proven to be very high for the types that are included in the vaccine and among women who haven t previously been infected by those types. Efficacy is much lower, though, in sexually experienced women because many of them will have already been infected. Therefore, we know that it s best to vaccinate girls before sexual experience, before they ve had any risk of being infected by these types of HPV. There s also some preliminary evidence that suggests that there s crossprotection even to types that are not included in the vaccine. HPV Vaccination 4

5 HPV vaccine strategies in low-resource settings Focus on older girls and young women who have not yet become sexually active. Catch-up campaigns for adult women are not likely to be cost-effective. Not yet clear if the vaccine protects men against HPV-caused cancers. Computer modelling suggests it is more cost-effective to invest in higher coverage among girls, rather than including boys. Our focus has been on older girls and young women who are not yet sexually active. We think that catch-up campaigns for adult women are not likely to be costeffective, because a high proportion of them may have already been infected with the types in the vaccine. It s not yet clear whether the vaccine will protect men against HPV-caused cancers, and it will be a couple of years before we have that information. Computer modeling, though, suggests that it s more cost-effective to invest in higher coverage for girls than to divert those doses of vaccine to covering boys, who may not benefit. HPV Vaccination 5

6 Integration of HPV vaccination and screening Current strategy Proposed strategy Schiffman M, Castle P. New England Journal of Medicine. 2005;353: Even with effective vaccination, we know that women will still need screening as they re in their thirties and forties. What would an integrated approach to screening look like, then? We can see on the slide that the current strategy has been repeated Pap smears, done all through the woman s life, from the age of sexual debut through her fifties. A new strategy would be to vaccinate these girls before they re sexually active, and then screen them only a few times in adult life. Computer modeling has suggested that this may be a much more efficient approach, and will actually be more effective and prevent more cancers. HPV Vaccination 6

7 HPV vaccination challenges Vaccine is expensive; subsidization required for low-resource settings. May need new systems for reaching girls in schools and other non-traditional venues. Low levels of provider and community understanding of need for vaccine. Difficult to explain: Partial efficacy of vaccine. Importance of three doses. Why given only to girls? Why at that early age? We know there will be challenges with HPV vaccination. As I mentioned, the vaccine is expensive, and some kind of subsidy is going to be required for lowresource countries. We also will probably need to develop new systems for reaching girls in schools, or in other non-traditional settings, because girls don t currently receive vaccines at this age. There are also low levels of provider and community understanding of the need for vaccine, or even of the burden of cervical cancer that occurs in their communities. The vaccine is also difficult to explain to some audiences. The partial efficacy of the vaccine, in other words, is that it only includes some of the types that cause cancer and not all of the types, the importance of having three doses to get full protection from the vaccine, the question of why the vaccine is given only to girls and not to boys, and why it s given at that early age. All of these need full explanation to communities and families so that they can support and feel comfortable with the vaccine. HPV Vaccination 7

8 Outstanding questions Duration of protection? Vaccination of HIV-positive girls? Co-administration with other vaccines? Alternative dosage schedules? Extent of cross-protection against other HPV types? Ultimate public-sector price? Will the GAVI Alliance and other development partners offer HPV vaccine? There are some outstanding questions that we don t have answers for yet, although research is under way to get them. The duration of protection is uncertain, although we expect it will be quite long. We don t know yet whether HIV-positive girls and young women will get full benefit from the vaccine. While we know the vaccine can be administered with at least one other vaccine hepatitis B we don t know yet whether it can be administered with other vaccines of interest. We don t know whether a schedule other than the three doses in six months could also be effective, so that countries might have more flexibility in how they design their programs. We don t know the extent of protection across other HPV types and how much we might benefit from that cross protection. The ultimate price in the public sector is uncertain, until negotiations are completed, and we don t know yet whether the GAVI Alliance and other development partners will offer the HPV vaccine. HPV Vaccination 8

9 Encouraging Signs Many communities are motivated: cancer, reproductive health, women s health, adolescent health, and immunization. Groups are mobilizing to educate and advocate for HPV vaccination. The World Health Organization, PATH, Harvard University, the International Agency for Research on Cancer, and others are coordinating efforts. International technical and financing bodies also are focusing on HPV vaccination. Despite these challenges and the questions that still remain, there are encouraging signs. Many communities of interest are motivated to increase access to the vaccine. The cancer community is involved in this, the reproductive health community is interested, women s health groups are interested, as are adolescent health groups. And immunization programs also recognize their role. Groups are mobilizing to educate and advocate for vaccination. Organizations like the World Health Organization, PATH, Harvard University, and the International Agency for Research on Cancer, among others, are coordinating their efforts on research and programmatic work to answer some of the outstanding questions. International technical and financing bodies also are focusing on HPV quite actively now. In summary, we have promising new HPV vaccines, we have feasible methods of delivering them to the girls who need them, and we have growing support from the communities, the countries, and the international agencies that will enable us to provide them and to reduce the burden of cervical cancer that falls so heavily on the developing world. HPV Vaccination 9