The Evolving Adult Immunization Platform William Schaffner, MD Vanderbilt University School of Medicine Nashville, TN

When meditating over a disease, I never think of finding a remedy for it, but, instead, a means of preventing it. Louis Pasteur (1822-1895)

Infant/Childhood immunization – one of the top public health success stories of the 20th century Diphtheria, tetanus, measles, mumps, rubella, polio, H. influenzae B, hepatitis B reduced by over 99% Pertussis, hepatitis A, select pneumococcal, varicella, rotavirus, influenza being reduced

Invigoration of Adult Immunization Build on success of infant/childhood, adolescent program New vaccines targeted at adults Recognition of the burden of adult vaccine-preventable disease

Burden of Adult Vaccine-Preventable Disease Influenza: 10-20% of US population affected annually 200,000 hospitalizations 36,000 deaths (average) Pneumococcal: 2,000-5000 meningitis 40,000+ bloodstream infections 150,000-300,000 pneumonia Pertussis: 1 million Cervical cancer: 10,000 Shingles: 1 million Adult deaths from vaccine-preventable diseases: 43,000

Reported Pertussis Cases ≥ 19 yrs 11–18 yrs < 11 yrs Reported Pertussis Cases 2004 provisional data

Tdap Vaccine Tetanus-Diphtheria – acellular Pertussis Licensed as one-time booster dose through age 64 Use Tdap at time of regular 10-year booster Individual protection against pertussis, tetanus, diphtheria Reduce community outbreaks Interrupt transmission to vulnerable infants by vaccinating adults (cocoon)

Human Papillomavirus Vaccine (Cervical Cancer) Licensed vaccine against 4 virus types (6, 11, 16, 18) for females 9-26 years Papillomavirus infection is precursor to cervical cancer Types 16, 18 account for 70% of cervical cancers Virus is transmitted by sexual contact Over half of women are infected during their lifetime Three-dose series

Invasive Cervical Cancer Cleared HPV Infection (~80%) Natural History of HPV Infection and Potential Progression to Cervical Cancer1 0–1 Year 0–5 Years 1–20 Years Initial HPV Infection Continuing Infection CIN 2/3 Invasive Cervical Cancer CIN 1 Key Point Infection with HPV will typically clear, but some infections with high-risk HPV types may ultimately lead to cervical cancer via a number of intermediate steps.   Background Following initial HPV infection, the course of progression to cervical cancer depends on the type of HPV. Low-risk HPV types (such as HPV 6 or 11) have a negligible risk of progressing but may persist.1 Overall, the majority of HPV infections spontaneously clear within the first 24 months.2 High-risk types (such as types HPV 16 and 18) are often associated with CIN 2 or higher lesions. The strong association of HPV 16 with CIN 2 or greater suggests that lesions caused by this infection evolve to CIN 2 without a prolonged period as CIN 1.1   Approximately 57% of low-grade lesions (CIN 1) will regress, 32% will persist, and 11% will progress. The risk of developing invasive cancer is estimated to be 1% in patients with CIN 1. Approximately 43% of CIN 2 lesions will regress, 35% will persist, 22% will progress to CIN 3, and 5% will progress to invasive cancer. The likelihood of CIN 3 regressing is about 32%, persistence is <56%, and rate of progression to invasive cancer is >12%.3 In studies of women with HPV infection who developed CIN 2 or 3, the initial abnormal smear was interpreted as CIN 2 or 3 in two thirds of cases,1,4 indicating that most CIN 3 lesions do not evolve from CIN 1.1 In a large, prospective study, mean times of progression from mild, moderate, or severe dysplasia to development of carcinoma in situ (CIS) were 58, 38, and 12 months, respectively.5    In general, CIN occurs at least a decade earlier than invasive cancer, supporting a concept of the temporal evolution of cervical cancer.3 Based on a Markov model that approximated age-specific incidence of cervical cancer and HPV infection-associated events, the peak prevalence of low-grade squamous intraepithelial lesions (LSIL) is at 28 years of age, at 42 years of age for HSIL, and at 48 years of age for cervical cancer.6 References 1. Pinto AP, Crum CP. Natural history of cervical neoplasia: Defining progression and its consequence. Clin Obstet Gynecol. 2000;43:352–362. 2. Ho GYF, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural history of cervicovaginal papillomavirus infection in young women. N Engl J Med. 1998;338:423–428. 3. Ostor AG. Natural history of cervical intraepithelial neoplasia: A critical review. Int J Gynecol Pathol. 1993;12:186–192. 4. Koutsky LA, Holmes KK, Critchlow CW, Stevens CE, Paavonen J, et al. A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection. N Engl J Med. 1992;327:1272–1278. 5. Richart RM, Barron BA. A follow-up study of patients with cervical dysplasia. Am J Obstet Gynecol. 1969;105:386–393. 6. Myers ER, McCrory DC, Nanda K, Bastian L, Matchar DB. Mathematical model for the natural history of human papillomavirus infection and cervical carcinogenesis. Am J Epidemiol. 2000;151:1158–1171. Cleared HPV Infection (~80%) 1. Pinto AP, Crum CP. Clin Obstet Gynecol. 2000;43:352–362.

HPV Vaccine Trial Randomized, placebo-controlled, double blind 27,000 volunteers 100% effective vs. CIN 2/3

Human Papillomavirus Vaccine CDC’s Advisory Committee on Immunization Practices (ACIP) June 29, 2006 Recommendations: Routine immunization of females at 11-12 years May be started as young as 9 years at discretion of provider/parent Vaccination of females up to age 26

Herpes Zoster (shingles) Vaccine Licensed for persons 60+ years of age Shingles – localized rash due to reactivation of latent chickenpox (varicella) virus Post-Shingles pain – extreme, debilitating pain lasting for months Vaccine licensed for persons 60+ years of age High potency live, attenuated varicella vaccine Boosts immunity

Shingles Prevention Study - 1 Randomized, placebo-controlled, double blind vaccine trial 38,546 volunteers at 22 sites; adults 60+

Shingles Prevention Study - 2 95% of volunteers completed study Follow-up <1 - 4.9 years; average 3 years Shingles reduced 51% 60-69 years 64% 70-79 years 41% 80+ 18% Post-shingles pain: 67%

Reported Acute Hepatitis B Incidence By Age Group: United States, 1990-2004 ≥20 years 94% decline 71% decline 12-19 years Cases per 100,000 <12 years Year

Reported Acute Hepatitis B Incidence By Age and Sex: United States, 2004 0.1 0.1 <5 Female Male 5-9 0.0 0.1 0.1 0.1 10-14 15-19 1.1 0.4 20-24 3.1 3.1 25-29 4.2 5.2 30-34 4.0 4.9 Age Group (Yrs) 35-39 4.4 5.4 40-44 3.6 4.9 45-49 2.7 4.0 50-54 2.0 3.2 55-59 1.3 2.9 60+ 0.8 1.4 Rate per 100,000

Hepatitis B Vaccine: ACIP Recommendations Expanded Risk Groups Sexual Transmission All sexually active persons not in a mutually monogamous relationship Persons evaluated or treated for STDs Men who have sex with men Sex partners of HBsAg-positive persons

Adult Immunization Influenza Tdap Pneumococcal HPV (cervical cancer) Hepatitis B Shingles Special circumstances, e.g. Travel, Health Care Worker

Adult Immunization Challenges Inadequate payment for vaccines and administration in both public programs and private medical insurance Lack of knowledge – both patients and providers Poor public health and private infrastructure for vaccine delivery