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THE JOURNAL OF FAMILY PRACTICE Michael E. Pichichero, MD Who should get Department of Microbiology and Immunology, Pediatrics, the HPV vaccine? and Medicine, University of Rochester Medical Center, Elmwood Pediatric Group, Latest recommendations from ACIP and others Rochester, NY Practice recommendations have not started sexual activity—are the • Consider recommending HPV vaccine for primary targets of immunization. How- 11- and 12-year-old girls in your practice, ever, the US Food and Drug Administra- before sexual activity puts them at risk tion also approved the use of Gardasil of viral infection (A). The FDA has also for girls as young as 9. Girls this age may approved the HPV vaccine for women require other vaccines, such as meningo- up to 26 years of age. ® Dowdencoccal conjugate Health and tetanus-diphtheria- Media acellular pertussis, and experience thus • If women older than 26 years ask to be far indicates no negative immune effects vaccinated, make sureCopyright they understandFor personalwith co-administration use only of vaccines.1,2 it is an off-label use for them (A). According to one study, vaccination Strength of recommendation (SOR) of the entire US population of 12-year-old A Good-quality patient-oriented evidence girls would prevent more than 200,000 B Inconsistent or limited-quality patient-oriented evidence C Consensus, usual practice, opinion, disease-oriented HPV infections, 100,000 abnormal Pap IN THiS ARTiCLE evidence, case series tests, and 3300 cases of cervical cancer.3 z How vaccination Parental as well as health care provider resexual adolescent girls and acceptance of HPV vaccines for adoles- prevents cervical sexually active women can now cents will be critical to the success of the cancer Plower their lifetime risk of cervical vaccination effort (see “What makes FPs Page 199 cancer, thanks to a newly available quad- recommend the HPV vaccine” on page rivalent vaccine (Gardasil) directed at hu- 201).4 z How HPV infection man papillomavirus (HPV). This gives us Practical issues. As with any new vac- progresses the opportunity to educate parents and cine added to the childhood/adolescent to cervical cancer adolescents (the primary target group for vaccination schedule, a host of issues will Page 200 the vaccine), many of whom remain un- need to be resolved to ensure adequate informed about the direct link between coverage. Factors likely to influence use of HPV infection and cervical cancer. HPV vaccine among adolescents are cost Ethical, cultural, social, and religious and reimbursement, and adherence to the issues that will require attention1 are be- 3-dose regimen that spans 6 months. yond the scope of this article. The American Academy of Pediatrics’ Committee on Infectious Diseases and the CORR e S p ON de NC e Advisory Committee on Immunization Michael E. Pichichero, MD, Elmwood Pediatric Group, 601 z Who should receive Practices (ACIP) recommends universal Elmwood Avenue, Box 672, the HPV vaccine? use of the HPV vaccine for girls, with a Rochester, NY 14642 Pre-adolescent and adolescent girls focus on 11- to 12-year-olds. The vaccine Michael_pichichero@ Girls ages 11 to 12 years—most of whom is also recommended for 13- to 26-year- urmc.rochester.edu www.jfponline.com VOL 56, NO 3 / MARCH 2007 197 For mass reproduction, content licensing and permissions contact Dowden Health Media. THE JOURNAL OF FAMILY PRACTICE TABLe z The rationale behind Factors that put women the recommendations at risk for HPV infection HPV transmission occurs easily with skin- to-skin contact.8–11 HPV can infect the Young age (peak age group: 20–24 years) external genitalia during non-intercourse Lifetime number of sexual partners sexual activities, including manual and First sexual intercourse at early age oral genital contact. Sexual intercourse is the most frequent mode of infection of Male partner sexual behavior the cervix. Condoms may help protect Smoking against transmission of HPV but are not 8,12 Oral contraceptive use fully effective. Adolescents are particularly vulnerable to Uncircumcised male partners HPV, but respond best to vaccine. The cervix Sources: Winer et al 2003;8 Schiffman and Castle is especially susceptible to HPV infection 2003;14 Insinga et al 2003.15 in adolescence because the squamous columnar cell junction transformation old girls and women who have received zone is more exposed. The adult cervix or completed the 3-dose vaccine series. is less susceptible to HPV than the ado- Why not vaccinate boys? HPV infec- lescent cervix because of the smaller area tion is highly prevalent in sexually ac- of cervical ectopy comprised of columnar tive men.5 The efficacy of vaccinating epithelial cells.13 However, in adolescents, boys against HPV infection is currently the immune response to HPV exposure is being explored.6 However, one model greater than in than adults. has suggested that vaccinating adoles- Risk for acquiring HPV infection. Risk cent males with a bivalent HPV vac- factors for acquiring HPV infection are cine would only slightly reduce the in- listed in the TaBLE.8,14,15 According to the cidence of cervical cancer cases beyond Centers for Disease Control and Preven- that achieved by vaccination of adoles- tion, sexually active men and women FAST TRACK cent girls, and with an extremely high have a 50% lifetime risk of acquiring Any sexually active cost-effectiveness ratio compared with HPV infection.16 An estimated 6.2 mil- female-only vaccination.5 lion people in the US become infected patient may benefit with HPV each year,16 and approximate- from vaccination Women ≤26 years ly 20 million currently harbor HPV infec- and should have Indications under FDA approval also in- tions.17 This estimate includes more than the opportunity clude women up to 26 years. Even adults 9 million sexually active adolescents and who have been sexually active for years young adults 15 to 24 years of age, the to receive it may not have been exposed to all high- group in which nearly 75% of new HPV risk HPV covered by the vaccine. infections occur.18 Among women <25 years of age, between 28% and 46% are Are women older infected with HPV.19,20 than 26 years eligible? Infection cannot always be cleared. Though FDA approval of the vaccine is Most HPV infections (whether high-risk for females aged 9 to 26 years, a recent or low-risk type) are asymptomatic and working group on HPV prevention con- are efficiently cleared (ie, no detection of cluded that any sexually active person DNA for a specific HPV type) by the im- may benefit from vaccination and should mune system.21,22 However, if the infec- have the opportunity to receive the vac- tion cannot be cleared or controlled by cine.1 Importantly, women older than 26 the immune system, it may become a per- years who request the vaccine should be sistent infection. made fully aware of its off-label applica- Persistent infection with HPV in- tion in their case. creases the probability of progression 198 VOL 56, NO 3 / MARCH 2007 THe JOURNaL OF FamILY PRactIce Who should get the HPV vaccine? How vaccination prevents cervical cancer Antibody Human papillomavirus Cervical cells Virus-like particle TOdd BuCK © 2006 After HPV vaccination, neutralizing antibodies are secreted from memory B cells, and bind to their target HPV type, preventing infection before it occurs, thereby blocking the For more about the initial step toward development of cervical cancer. 15 high-risk oncogenic types. Papillomaviruses such as HPV are nonenveloped, development of double-stranded, DNA viruses. They infect cutaneous and mucosal epithelial tissues. More HPV vaccines than 100 HPV types have been identified,3 about 30 to 40 of which are spread by sexual Go to our website at contact.4 Of the many known HPVs, only 15 are high-risk oncogenic types (16, 18, 31, 33, www.jfponline.com 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, and 73) that can cause cervical cancer.5.6 Of these high-risk oncogenic types, HPV 16 and 18 account for about 70% of all cervical cancers.7 The new HPV vaccines (Gardasil and Cervarix) both contain virosomal antigens to vaccinate against HPV types 16 and 18. Persistent infection with these high-risk HPV types is necessary for the development of cervical cancer. Chronic infection with low-risk HPV types (eg, HPV 6 or 11) may lead to the development of anogenital warts and other low- grade genital abnormalities, as well as laryngeal cancer or recurrent respiratory papilloma- tosis. Gardasil also contains virosome antigens for these 2 HPV types. Warts on the hands are usually attributable to HPV 7.8 to high-grade cervical intraepithelial Viral integration is a necessary step neoplasia (CIN) and invasive carcino- in the malignant transformation of HPV ma (FIGURE).18–19 Evidence also increas- infection; infection may progress from ingly shows that high-risk HPV types residential to episomal, and, finally, to likely cause anal, penile, scrotal, vul- an integrated form. Residential infection var, vaginal, and some head and neck typically occurs a minimum of 6 weeks cancers.25 from exposure, can persist without de- www.jfponline.com VOL 56, NO 3 / MARCH 2007 199 THE JOURNAL OF FAMILY PRACTICE FIGURe How HPV infection progresses to cervical cancer 0–1 Year 0–5 Years 0–20 Years Continuing infection CIN 2/3 Invasive cervical cancer Initial HPV infection CIN 1 Cleared HPV infection Adapted with permission from Pinto and Crum 2000 23 and Schlecht et al 2001.24 tection for decades, and can be low risk z The case for vaccination or high risk. In the episomal state, virally plus screening active HPV is located in the cell nucleus, It will likely take at least a decade to as- separate from the human DNA.