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

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

3. 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

4. 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

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

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

7. 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)

8. 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

9. 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.

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

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

12. 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

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

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

15. 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

16. 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

17. 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

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

19. 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