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

Sexual Activity

Risk of HPV Transmission Most consistent predictor of HPV infection is number of sexual partners –Females age with median 1.4 lifetime male partners; age median is 2.8 –Of sexually active women, 5.7% of 9 th graders & 20.2% of 12 th 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 years Catch up vaccination for age 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

Kimberlin D and Whitley R. N Engl J Med 2007;356: Host Factors in Latent VZV Infection and Reactivation

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 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, vaccinations to prevent single case of post-herpetic neuralgia –Cost per prevented case $6,405

VZV Vaccine Questions Vaccinate 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: