HPV Vaccine: Conventional View

These are the latest conventional guidelines for the HPV vaccine, recommended routinely for 11-12 year old girls. I will separately post a counterpoint view by holistic gynecologist Christiane Northrup, MD. SG

Guidelines Issued for HPV Vaccine Use to Prevent Cervical Cancer

News Author: Laurie Barclay, MD
CME Author: Penny Murata, MD

January 25, 2007 — The American Cancer Society (ACS) has issued guidelines for the use of the prophylactic human papillomavirus (HPV) vaccine to prevent cervical intraepithelial neoplasia (CIN) and cervical cancer. The new guidelines, published in the January/February issue of CA: Cancer Journal for Clinicians, address who should be vaccinated and at what age, and summarize policy and implementation issues and implications for screening, based on a formal review of the available evidence.
"Cervical cancer screening has successfully decreased squamous cell cervical cancer incidence and mortality," write Debbie Saslow, PhD, of the American Cancer Society in Atlanta, Georgia, and colleagues. The American Cancer Society (ACS) Guideline for the Early Detection of Cervical Cancer was last reviewed and updated in 2002; for the first time, those recommendations incorporated options including liquid-based cytology and human papillomavirus (HPV) DNA testing. Since that time, two vaccines against the most common cancer-causing HPV types have been developed and tested in clinical trials."
A panel of experts reviewed numerous studies published on the efficacy of these vaccines as well as issues related to policy and implementation.
Specific recommendations for HPV vaccination are as follows:
1. Routine HPV vaccination is recommended for girls 11 and 12 years old.
2. Girls as young as age 9 years can receive HPV vaccination.

3. HPV vaccination is also recommended for teenaged girls 13 to 18 years old to catch up on missed vaccine or to complete the vaccination series.

4. The evidence is insufficient at this time to recommend for or against universal vaccination of women 19 to 26 years old in the general population. A decision about whether to vaccinate a woman 19 to 26 years old should be based on an informed discussion between the woman and her healthcare provider regarding her risk for previous HPV exposure and her potential benefit from vaccination. Ideally, the HPV vaccine should be administered before potential exposure to genital HPV through sexual intercourse, because the potential benefit is likely to decrease with an increasing number of lifetime sexual partners.

5. HPV vaccination is not currently recommended for women older than age 26 years or for males.

6. Screening for CIN and cervical cancer should continue in both vaccinated and unvaccinated women, according to current ACS early detection guidelines.
"If duration of immunity is substantial or can be extended adequately through booster vaccinations, the high vaccine efficacy observed in Phase II and III studies suggests that female populations receiving prophylactic immunization will experience a reduction in the morbidity and mortality associated with HPV-related anogenital diseases," the authors write. "The promise of prophylactic vaccines from a broad public health perspective, however, can be realized only if vaccination can be achieved for those groups of women for whom access to cervical cancer screening services is most problematic."
Other screening recommendations are for a preventive healthcare visit, in which vaccination is discussed or offered; this represents an appropriate opportunity to offer Papanicolaou test screening to sexually active patients. HPV testing is not recommended before vaccination.
To foster vaccine implementation and use, the authors recommend public health and policy efforts to ensure access and encourage high HPV vaccine coverage for all racial, ethnic, and socioeconomic groups. To maximize adherence to vaccination recommendations, strategies should include coadministration with other recommended adolescent vaccines, once sufficient safety data are available.
The use of noncomprehensive visits, such as minor illness visits, camp/sports physical visits, and alternative vaccination sites is encouraged for adolescents unable to access comprehensive preventive care.
The guidelines mandate education of providers, policymakers, parents, adolescents, and young women about cervical cancer prevention and early detection, including the need for regular screening even after vaccination.
Recommended research directions consists of ongoing research and surveillance in diverse populations, including research on duration of protective immunity, population- and lesion-based changes in type-specific prevalence for the full spectrum of carcinogenic and noncarcinogenic genital HPV types, changes in Papanicolaou test performance characteristics, changes in screening practices and behaviors, comprehensive surveillance for reproductive toxicities, increasing vaccine coverage and acceptability, and impact on safe sexual behavior.
Other research goals include evaluation of the safety and efficacy of prophylactic HPV vaccine for the prevention of other anogenital cancers and head and neck cancers in males, as well as in females, and designs for sustainable vaccination programs in less-developed countries.
"The protective effect of vaccination that is successfully provided to adolescent and young women who are unlikely to undergo regular Pap [Papanicolaou] screening will be of greater magnitude than that provided to women who will undergo regular screening regardless," the authors conclude. "Even as HPV vaccination for the prevention of cervical cancer is introduced and promoted, it remains critical that women undergo regular screening regardless of whether they have been vaccinated."
CA Cancer J Clin. 2007;57:7-28.
Clinical Context
According to a report by Pagliusi published by the World Health Organization, cervical cancer is the second most common cause of cancer death worldwide. In the December 1999 issue of Clinical Obstetrics and Gynecology, Sawaya and Washington noted that the incidence of cervical cancer would be 2 to 3 per 100,000 even with optimal screening. HPV types 16 and 18 cause 70% of cervical cancers, according to Munoz and colleagues in the February 6, 2003, issue of The New England Journal of Medicine, and 50% to 60% of CIN grade 2 and 3, according to Clifford and colleagues in the July 7, 2003, issue of the British Journal of Cancer.
Two HPV vaccines have been developed to decrease HPV-related cervical, penile, vulvar, vaginal, and anal precancerous and cancerous lesions, genital warts, and laryngeal papillomatosis: Gardasil (Merck & Co, Inc) is a quadrivalent vaccine to prevent HPV types 6, 11, 16, and 18; and Cervarix (GlaxoSmithKline) is a bivalent vaccine to prevent HPV types 16 and 18.
An expert panel organized by the ACS reviewed the published and unpublished data on HPV vaccines and the prevention of cervical cancer and precancerous lesions. Panel members put forth expert opinions in cases of insufficient evidence. The recommendations were discussed and voted on by the ACS Gynecologic Cancer Advisory Group and the National Board of Directors. The ACS guidelines focus mainly on Gardasil, which is licensed by the US Food and Drug Administration.
Study Highlights
• Cervical cancer incidence is higher in some groups because of social, cultural, and healthcare access barriers.
• Progression from HPV infection to invasive cancer takes an average of 20 years.
• Genital HPV transmission usually occurs within a few years after onset of vaginal or anal intercourse.
• Study enrollment criteria limited the lifetime number of sex partners (mean, 2; maximum, 4) and histories of cervical abnormalities.
• 2 Gardasil phase 3 efficacy substudies were conducted on women who complied with vaccine regimen and did not have type-specific HPV infection:
• Females 15 to 26 years old had 100% vaccine efficacy in prevention of HPV 16/18-related CIN 2/3 and adenocarcinoma in situ.
• Females 16 to 23 years old had 100% vaccine efficacy in prevention of HPV 6/11/16/18-related external genital warts, vulvar/vaginal intraepithelial neoplasia, and cervical lesions with follow-up of 1.5 years.
• Results from intent-to-treat analyses of Gardasil included women who received at least a 1 vaccine dose and had current or past HPV infection, according to polymerase chain reaction or serology
• Cervarix had 100% efficacy in preventing HPV 16/18-related CIN in females 15 to 25 years old followed up to 4.5 years
• Safety results for Gardasil and Cervarix from phase 2b randomized controlled trials:
• Injection site adverse events were more common and intense in Gardasil vs placebo subjects (83% vs 73%) and more common in Cervarix vs placebo subjects (94% vs 88%).
• Most common systemic adverse events occurred in 69% of both Gardasil and placebo subjects and in 86% of both Cervarix and placebo subjects.
• Serious vaccine-related events occurred in 5 Gardasil and 2 placebo subjects.
• Up to 0.2% of subjects discontinued study because of adverse events.
• No vaccine-related deaths occurred in Gardasil or Cervarix subjects.
• In women who became pregnant within 30 days' postvaccination, congenital anomalies occurred in 5 of Gardasil group and none of placebo; no data were published for Cervarix subjects.
• Pregnancy registry postmarketing to further evaluate effects has been proposed.
• Duration of vaccine-related HPV immunity is not known.
• Youngest subjects were 9 years old for safety and immunogenicity studies, 16 years old for Gardasil efficacy studies, and 15 years old for Cervarix efficacy studies.
• Insufficient evidence exists to recommend for or against routine vaccination for women 19 to 26 years old, but those who have not had sexual intercourse would benefit from vaccine. Efficacy data for HPV 16/18-related CIN 2/3 in women with more than 4 lifetime sex partners are lacking.
• Male subjects 9 to 15 years old were included in Gardasil safety, immunogenicity, and ongoing efficacy trials; male vaccination might not be cost-effective in cervical cancer prevention, but might be more effective in low-vaccination areas.
• Current cervical cancer screening recommendations should continue.
• Vaccination effects on cervical cancer rates will not be apparent until subjects reach the age of 48 years, the median age of cervical cancer diagnosis.
• HPV testing before vaccination is not recommended.
• Recommendations for vaccine implementation include distribution to underserved areas through free programs and at routine healthcare visits for girls at age 11 or 12 years.
• Limitations of HPV vaccines include lack of protection against all carcinogenic HPV types, noncompliance, and need for studies in HIV-infected people.
Pearls for Practice
• HPV vaccine is recommended routinely for girls 11 and 12 years old and for catch-up for teenaged girls 13 to 18 years old. It can be given to girls as young as 9 years. However, data are inadequate to support universal HPV vaccine for women 19 to 26 years old, but the vaccine is likely less beneficial in females with more lifetime sexual partners.
• Females who are vaccinated and unvaccinated with HPV vaccine should continue to undergo screening for CIN and cancer, as recommended in current ACS guidelines.