# Presentation: 671272

## Human Papillomavirus (HPV) and HPV Vaccine

**Revised December 2006**
**Update April 2007**

**Epidemiology and Prevention of Vaccine-Preventable Diseases**
**National Immunization Program**
**Centers for Disease Control and Prevention**

## Human Papillomavirus (HPV)

**Small DNA virus**
**More than 100 types identified based on the genetic sequence of the outer capsid protein L1**
**40 types infect the mucosal epithelium**

## Human Papillomavirus Types and Disease Association

**nonmucosal/cutaneous**
**(~60 types)**

** ****skin warts (hands and feet)**

**mucosal/genital(~40 types)**

**high-risk types**
**16, 18, 31, 45**
**(and others)**

**low-risk types**
**6, 11**
**(and others)**

**low grade cervical            ****	****abnormalities**
**cancer precursors**
**anogenital cancers**

**low grade cervical**
** ****abnormalities**
**genital warts**
**laryngeal papillomas**

## HPV-Associated Disease

| Type | Women | Men |
| --- | --- | --- |
| 16/18 | 70% of Cervical Cancer
70% of Anal/genital Cancer | 70% of Anal Cancer
Transmission to women |
| 6/11 | 90% of Genital Warts
90% of RRP lesions | 90% of Genital Warts
90% of RRP lesions
Transmission to women |

**HPV-Associated Disease**

## Natural History of HPV Infection

**Within 1 Year**

**1-5 Years**

**Up to Decades**

**Initial****HPV Infection**

**Persistent**
**Infection**

**CIN 2/3**

**Cervical Cancer**

**CIN 1**

**Cleared HPV Infection**

**Natural History of HPV Infection**

## HPV Clinical Features

**Most HPV infections are asymptomatic and result in no clinical disease**
**Clinical manifestations of HPV infection include:**
**anogenital warts**
**recurrent respiratory papillomatosis**
**cervical cancer precursors (cervical intraepithelial neoplasia**
**Cancer (cervical, anal, vaginal, vulvar, penile, and some head and neck cancer)**

## Cancer Attributable to HPV - 2002

**Cervical**
**Anal**
**Vulvar/vaginal**
**Penile**
**Oral/pharynx**

**Cancer Attributable to HPV - 2002**

**Estimated**
_**Cases**_
**12,000**
**3,700**
**4,480**
**1,000**
**10,000**

**Attributable**
_**Fraction**_
**100%**
**90%**
**40%**
**40%**
**12%**

## HPV-associated Conditions

_**HPV 16, 18**_
**Cervical cancer**
** ****- High/low grade cervical **
**    ****abnormalities**
**Anal, Vulvar, Vaginal, Penile          **
**Head and neck cancers            **
_**HPV 6, 11**_
**Low grade cervical **
** ****abnormalities**
**Genital warts**
**RRP**

**Estimated %**
**70%**
**30%-50%**
**10%**

**10%**
**90%**
**90%**

## HPV Epidemiology

**Reservoir****	****	****	****Human**** **
**Transmission****	****	****Direct contact,**
**	****	****	****	****	****	****usually sexual**
**Temporal****	****	****	****None**** pattern****	****	****	**
**Communicability****	****Presumed to be high**

## HPV Disease Burden in the United States

**Anogenital HPV is the most common sexually transmitted infection in the US**
**Estimated 20 million currently infected**
**6.2 million new infections/year**
**Common among adolescents and young adults**
**Estimated 80% of sexually active women will have been infected by age 50**
**Infection also common in men**

## Cervical Cancer Disease Burden in the United States 

**Cervical Cancer Disease Burden in the United States **

**The National Cancer Institute estimates that in 2007:**
**11,150 new cervical cancer cases **
**3,670 cervical cancer deaths**
**Almost 100% of these cervical cancer cases will be caused by one of the 40 HPV types that infect the mucosa**

## Cervical Cancer Screening

**Cervical cancer screening – no change **
**30% of cervical cancers caused by HPV types not prevented by the quadrivalent HPV vaccine**
**Vaccinated females could subsequently be infected with non-vaccine HPV types  **
**Sexually active females could have been infected prior to vaccination **
**Providers should educate women about the importance of cervical cancer screening **

## Human Papillomavirus Vaccine

**HPV L1 major capsid protein of the virus is antigen used for immunization **
**L1 protein expressed in yeast cells using recombinant technology**
**L1 proteins self-assemble into virus-like particles (VLP)**
**Noninfectious and nononcogenic**

## HPV Vaccine Efficacy*

| Endpoint |    Efficacy |
| --- | --- |
| HPV 16/18-related
CIN2/3 or AIS
 |   100 |
| HPV 6/11/16/18
related CIN
 |   95 |
| HPV 6/11/16/18
related genital warts |   99 |

***Among 16-26 year old females. ****CIN – cervical intraepithelial neoplasia; AIS – adenocarcinoma *****in situ***

## High efficacy among females without evidence of infection with vaccine HPV types
No evidence of efficacy against disease caused by vaccine types or which participants were infected at the time of vaccination 
Prior infection with one HPV type did not diminish efficacy of the vaccine against other vaccine HPV types

**No evidence of efficacy against disease caused by vaccine types or which participants were infected at the time of vaccination **
**Prior infection with one HPV type did not diminish efficacy of the vaccine against other vaccine HPV types**

**HPV Vaccine Efficacy**

## Correct and consistent condom use may have a protective effect on HPV acquisition, reduce the risk for HPV-associated diseases, and mitigate the adverse consequences of infection with HPV.

**This statement is required by section 317 of the**
**Public Health Service Act, 42 U.S.C., 243 **

## Routine HPV Vaccination Recommendations 

**ACIP recommends routine vaccination of females 11-12 years of age **
**The vaccination series can be started as young as 9 years of age at the clinician’s discretion**
**“****Catch-up” vaccination recommended for females 13 through 26 years of age**

***MMWR***** 2007;56(RR-2):1-24**

## HPV Vaccination Schedule 

**Routine schedule is 0, 2, 6 months**
**Minimum intervals**
**4 weeks between doses 1 and 2 **
**12 weeks between doses 2 and 3**
**Do not restart the series if the schedule is interrupted**
**Administer at same visit as other age-appropriate vaccines (e.g., Tdap, MCV)**

***MMWR***** 2007;56(RR-2):1-24**

## Quadrivalent HPV Vaccine 

**HPV vaccine should not be administered to males and women older than 26 years**
**Limited safety and immunogenicity data available**
**No clinical efficacy data**
**Off-label use not recommended**
**Studies of clinical efficacy in progress now**

## HPV VaccineSpecial Situations*

**Equivocal or abnormal Pap test**
**Positive HPV DNA test**
**Genital warts**
**Immunosuppression **
**Breastfeeding**

** *****Vaccine can be administered****  **

## HPV Vaccine – Special Situations*

**Females 26 years of age or younger with an equivocal or abnormal Pap test, positive HPV DNA, or genital warts may be vaccinated**
**Vaccine will have no effect on existing disease or infection**
**Females 26 years of age or younger who are lactating/breastfeeding or are immunocompromised may be vaccinated**
**Not recommended for pregnant women**

***MMWR***** 2007;56(RR-2):1-24**

## HPV VaccineAdverse Reactions

**Local reactions****	****	****84%**
**   ****(pain, swelling)**
**Fever ****	****	****	****	****	****10%***
**No serious adverse reactions reported**

***similar to reports in placebo recipients (9%)**

## HPV VaccineContraindications and Precautions

**Contraindication**
**Severe allergic reaction to a vaccine component or following a prior dose **
**Precaution**
**Moderate or severe acute illnesses (defer until symptoms improve)**

## HPV Vaccination During Pregnancy 

**Initiation of the vaccine series should be delayed until after completion of pregnancy**
**If a woman is found to be pregnant after initiating the vaccination series, remaining doses should be delayed until after the pregnancy  **
**If a vaccine dose has been administered during pregnancy, there is no indication for intervention**
**Women vaccinated during pregnancy should be reported to Merck registry (800.986.8999)**

***MMWR***** 2007;56(RR-2):1-24**

## HPV Vaccine Storage and Handling

**Store at 36°F-46°F (2°C-8°C)**
**Protect from light**
**Do not expose to freezing temperature**
**Remove from refrigeration immediately before administration**

## National Immunization ProgramContact Information

**Telephone****	****	****800.CDC.INFO**** **
**Email****	****	****	****nipinfo@cdc.gov**** **
**Website****	****	****www.cdc.gov/nip**