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HPV-16/18 vaccine (Gardasil, Cervarix)

Tradename: Gardasil, Cervarix [13] Indications: 1) Gardasil 9 [34] approved for prevention of cervical cancer caused by HPV types 16, 18, 31, 33, 45, 52 & 58, & for prevention of genital warts caused by HPV types 6 or 11 - earlier Gardasil active against HPV types 6, 11, 16, 18; & Cervarix against HPV types 16, 18 2) routine administration to all females 9-26 years of age* a) start age 11 or 12 [17] b) final dose can be completed after 26 years of age if vaccinated late 3) efficacious in women 24-years of age 4) may not be cost-effective in women > 30 years of age [11] 5) FDA approved for use in males (Gardasil) [12] a) can prevent anal intraepithelial neoplasia in men who have sex with men [20] b) recommended for boys age 11 & 12 years [21,22,23] c) recommended for males age 13-21 years (13-26 years) [64] who have not yet been immunized or have not finished the 3-dose series [17,22,23] d) failure of herd immunity from vaccination of girls to better protect men is due to lack of protection for men who have sex with men [40] 6) FDA-approved for use in adults up to 45 years of age [57] - extending recommended age to 45 years would only slightly lower rates of HPV-associated disease, but greatly increase costs [61] 7) prevents some if not most cases of cervical cancer - 3 full doses reduces risk of high-grade cervical lesions by 46%; number needed to treat = 125 [30] 8) reduces burden of genital warts (Gardasil) in men & women [14,18] 9) may help treat oral warts (case report) [42] 10) HIV1 infection (CD4 count > 200/uL) 11) vaccine programs also advantageous for unvaccinated people through herd immunity [59] * in Scotland, efforts to vaccinate 12 & 13 year old girls has resulted in a 90% reduction in the prevalence of cervical intraepithelial neoplasa grade 3 or worse findings on cervical smears at age 20; prevalence was 0.59% among unvaccinated versus 0.06% in vaccinated 20 year old women [58] Contraindications: - does NOT eliminate need for Pap Smears - current recommendations for 9 valent vaccine require only HPV DNA testing (see screening for cervical cancer) - not cost-effective after age 30 - safe during pregnancy [53] - no increase in risk of spontaneous abortion, stillbirth, major birth defect, low birth weight, or preterm birth [53] Benefit/risk: - risk for cervical cancer reduced by 88% among women who were immunized before age 17 [63] - risk of progression of cervical intraepithelial neoplasia lowest in girls vaccinated prior to age 15 years [66] - number needed to treat (NNT) - 800 boys age 12 would need to be vaccinated to prevent 1 cancer (at a 60% coverage rate for girls) [40] - HPV vaccine with both direct efficancy & herd immunity after 15 years [65] Epidemiology: - 57% of girls & 35% of boys have received at least 1 dose of HPV vaccine [40] - incidence of HPV declined by more than 1/2 in girls after introduction of HPV vaccine [26] - reduced incidence of cervical dypsplasia in girls age 14-17 years (NNT = 175) [39]* - prevalence of HPV types (6, 11, 16, & 18) has dropped 64% in girls 14-19 years since thex HPV vaccine was introduced [43] * why were Pap smears done on girls of this age? Dosage: - 2 IM injections separated by 6-12 months for children who start HPV vaccination between ages 9 & 14 [48,50,52] - 2 doses as good & more cost-effective than 3 [19,25,29,35,48,54] - after 24 months, antibody levels against HPV type 16 the same for 2 doses vs 3 doses [25], but for HPV type 18, antibody levels lower for 2 doses vs 3 doses [25] - women < 26 years & men 21 years who began HPV vaccination before age 15 & received 2 doses at least 5 months apart do not need another dose [51] - 3 IM injections for females 15-26 & for males 15-21 years of age & for immunocompromised patients - 2nd dose 1-2 months after 1st dose & the 3rd dose 6 months after 1st dose [50] - 1 or 2 doses may be as effective as 3 doses preventing cervical HPV type 16/18 infections [41] - a single dose may be effective [62] - 9-valent vaccine available - complete series with 9-valent vaccine [42] - cost of quality-adjusted years of life for vaccination with 9-valent vaccine after completion of quadrivalent vaccine is estimated to be > $100,000 [42] (more for women > 18 years of age; may be no benefit for men) Shelf life of 3 years (refrigerated) Adverse effects: 1) no serious adverse effects reported by manufacturer 2) about as safe as any other vaccine [10] - no serious adverse effects [27] 3) incidence of adverse effects: 0.054% [10] 3) pain a) known as the most painful childhood vaccination b) inability to drive with or sleep on the affected arm for up to a day [8] c) pain may be diminished if administered prior to other vaccines administered the same visit [33] 4) fainting, syncope (0.008%) 5) vomiting, dehydration 6) venous thromboembolism (0.002%) [10] - no increased risk for venous thromboembolism [31] 7) Guillain-Barre syndrome 8) no increased risk of miscarriage after HPV vaccine [16] 9) does not increase sexual activity in teenage girls [24] - does not increase sexually-transmitted disease in teenage girls [36] Mechanism of action: - the investigational vaccines contained human papilloma virus type 16-like particles [1] or type 16 & type 18 virus particles [2] - it is NOT a live virus vaccine - Cervarix uses a different adjuvant than Gardasil which might give longer immunity; it also seems to offer more cross-protection against some HPV types that are not included in the vaccine - Gardasil provides protection against HPV 6 & 11, causative agents of genital warts in men & women Notes: - cost $120/dose ($360 for series) - brief messaging to parents may promote HPV vaccination [46] - announcing that adolescents are due for HPV vaccination may be more effective than a conversation with families in promoting HPV vaccination [49] - screening cervical cancer may be less frequent for women who have completed HPV vaccination (see screening for cervical cancer) [47] - legislation to increase HPV vaccination does not seem to affect adolescent sexual behavior [56]

General

vaccine

References

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  4. CDC Advisory Committe on Immunization Practices
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  8. Associated Press, Jan 4, 2008
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