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Herpes Papillomavirus (HPV) and Varicella-zoster Virus (VZV) Vaccination. Ellen Barbouche, MD Primary Care Conference 18 April 2007. Learning Objectives. No financial disclosures Review HPV and VZV vaccination efficacy, adverse effects, and guidelines. Case 1.
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Herpes Papillomavirus (HPV) and Varicella-zoster Virus (VZV) Vaccination Ellen Barbouche, MD Primary Care Conference 18 April 2007
Learning Objectives No financial disclosures Review HPV and VZV vaccination efficacy, adverse effects, and guidelines
Case 1 • 24 year old female for preventive health exam • “Should I get that HPV vaccine?” • History of cervical dysplasia treated with cryosurgery • On oral contraceptive
HPV virulence • Low risk types (6 and 11) cause low grade cervical cell changes and genital warts • High risk types detected in 99% of cervical cancers • Types 16 and 18 cause 70% of cervical cancers • HPV associated with cancers of vulva, vagina, penis, anus, oral cavity and pharynx
Risk of HPV Transmission • Most consistent predictor of HPV infection is number of sexual partners • Females age 15-19 with median 1.4 lifetime male partners; age 20-24 median is 2.8 • Of sexually active women, 5.7% of 9th graders & 20.2% of 12th graders had >4 sex partners
HPV Natural History • 70% of new infections clear within 1 year, 90% within 2 years • Persistent infection varies by HPV type
HPV prevention • Correct and consistent condom use reduces HPV rates by 70% • Abstinence • Quadrivalent (types 6,11,16,18) vaccine
HPV Vaccine Administration • 3 dose series: now, 2 month and 6 months • Contains no thimerosal or antibiotic
HPV Vaccine Efficacy • 95.2% efficacy against CIN 1, CIN 2/3, or adenocarcinoma in situ • 98.9% against HPV 6,11,16, or 18 genital warts • 89.5% against persistent HPV infection • 100% effective against other types in women previously HPV exposed • Duration of protection studies now at 3 years
HPV Vaccine Immunogenicity • After completion of 3 doses, >99.9% of participants had antibody to all 4 HPV types • Antibody titers after vaccination are higher than those after natural infection
HPV Vaccine Adverse Events • 83.9% pain • 2.8% severe pain • 2% swelling • 0.9% erythema • 4% fever • <0.1% serious events, vaccine equal to placebo
HPV Cost Effectiveness • Assume $377 per dose series, 90% lifetime efficacy: 58% reduction in lifetime cervical cancer risk and $24,300 per quality-adjusted life-year (QALY) • Assume $300 per dose series, $100 booster at 10 years, same efficacy: 62% reduction in lifetime cervical cancer risk and $14,600 per QALY
HPV Vaccine Recommendations • Routine vaccination at 11-12 years • Catch up vaccination for age 13-26 Would you vaccinate Case 1?
Case 2 • 71 year old male for hypertension follow up • “Should I get that shingles vaccination?” • Meds: Aspirin and Atenolol • PMH: HTN and THA
Varicella-Zoster Virus (VZV) • Reactivation of latent VZV causes herpes zoster (shingles) • Risk of zoster increases with increasing age, beginning at 50 • Zoster develops in 30% of people over lifetime, and up to 50% of 85 year olds
VZV Infectivity in US(prior to use of primary varicella vaccination)
VZV Complications • Cranial or peripheral verve palsies • Encephalitis • Myelitis • Post-herpetic neuralgia • Most likely to occur if host > age 50 • Of people > age 60 with zoster, 40% have post-herpetic neuralgia
Host Factors in Latent VZV Infection and Reactivation Kimberlin D and Whitley R. N Engl J Med 2007;356:1338-1343
VZV Vaccine Strength • Varivax 1,350 plaque-forming units/dose • Proquad (MMR + VZV) 9,772 pfu/dose • Zostavax 19,400 pfu/dose • Higher titer due to decreased cell-mediated immunity in older population
VZV Vaccine Efficacy Evidence • 38,546 subjects over age 60 followed for 3 years • Incidence of zoster 5.4 vs. 11.1 cases per 1,000 person-years, vaccinated vs. placebo (51% decrease) • Post-herpetic neuralgia: 0.5 vs.1.4 cases per 1,000 person-years, vaccinated vs. placebo (67% decrease)
Adverse Effects of VZV Vaccine(All % vaccinated vs. placebo) • Injection site phenomena: • Varicella-like rash (0.1% vs. 0.04%) • Erythema (36% vs. 7%) • Pain or tenderness (35% vs. 9%) • Swelling (26% vs. 5%) • Pruritus (7% vs. 1%) • Cardiac events (0.6% vs. 0.4%)
VZV Vaccine Contraindications • Prior anaphylactic reactions to gelatin, neomycin or other vaccine component • Immunodeficiency condition or immune suppressive therapy • Active, untreated tuberculosis • Pregnancy
VZV Vaccine Cost • $14,877-$34,852 per QALY (assumes $150 per vaccination) • 17 vaccinations to prevent single case of zoster • Cost per prevented case $3,330 • 31 vaccinations to prevent single case of post-herpetic neuralgia • Cost per prevented case $6,405
VZV Vaccine Questions • Vaccinate 50-59 year olds • Shifting VZV epidemiology • Primary vaccination • Duration of zoster vaccine efficacy • Immunocompromised quagmire • Diabetes mellitus • Steroids • Anticipated immunesuppression • Prior zoster
VZV Vaccine Recommendations • Single dose to adults age > 60, regardless of prior varicella history Would you vaccinate Case 2?
Bibliography Markowitz, LE et al. Quadrivalent Human Papillomavirus Vaccine. MMWR. 2007:56(RR02);1-24. Kimberlin, DW and Whitney, RJ. Varicella-zoster Vaccine for the Prevention of Herpes Zoster. NEJM. 2007;356:1338-43.