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Quadrivalent Human Papillomavirus Vaccine as a Travel Vaccine
Abstract & Commentary
By Michele Barry, MD, FACP
Professor of Medicine and Global Health Yale University School of Medicine
Dr. Barry receives no funding from any issue related to this commentary. She is a consultant for Ford Foundation and had received funding from Johnson and Johnson and Sanofi-Pasteur.
Synopsis: In June, 2006, the FDA licensed the first human papillomavirus vaccine (HPV) to prevent cervical cancer and other HPV associated cancers: vaginal, urethral and oral tumors. Is this yet another travel vaccine for our patients?
Source: Markowitz LE, et al. Quadrivalent human papillomavirus vaccine. Recommendations of the advisory committee on immunization practices. MMWR March 23, 2007;Vol.56/RR-2.
HPV is the most common sexually transmitted infection in the United States; an estimated 6.2 million persons are newly infected every year. Although over 100 HPV types have been identified the quadrivalent vaccine Gardasil® made by Merck protects against 4 HPV types (6, 11, 16, 18). However, types 16 and 18 are responsible for 70% of cervical cancers and types 6 and 11 are associated with 90% of all genital warts. This prophylactic vaccine made from non-infectious HPV-derived particles is recommended for females ages 9 - 26 years. Ideally the vaccine should be administered before onset of sexual activity. Administration of the Merck vaccine, which has no thimerosal, the organomercury preservative, requires 2 booster doses (0.5 ml intramuscularly) at 2 and 4 months. Duration of efficacy thus far has only been demonstrated for 5 years — future booster doses may be needed. The vaccine is available in a single dose vial or a prefilled syringe. Storage is at 2° C - 8° C (36° F - 46° F) and it should not be frozen. Vaccination can be administered for women with abnormal pap smears who are HPV positive to protect against other HPV infections, but it will not help or change the medical course of these abnormal pap smears. The private sector list price of the vaccine is $119.75 per dose — $360 for the full 3 vaccine doses.
During these times of globalization, college and high school students are traveling the world and are inundating travel health clinics. Experience of freedom while being away from home and school leads to increased sexual activity sometimes called "situational disinhibition".1 The travel clinic visit presents the perfect time to offer HPV vaccine as trips often coincide with increased sexual activity with new partners or travel companions. Unfortunately, the students' traveling schedules often do not allow enough time for full immunization, but certainly a first dose and educational materials about the benefits of full vaccination can be offered. Such educational materials can instruct the traveler that in addition to cervical cancer, HPV infection is also associated with anogenital cancers such as cancer of the vulva, vagina, penis and anus. Studies support a role for HPV also causing a subset of oral cavity and pharyngeal cancers. HPVs are non-enveloped double-stranded DNA viruses that are classified as "types" designated on the basis of nucleotide sequences with numbers assigned in order of their discovery.
Genital HPV infection is primarily transmitted soon after an individual's sexual activity begins. One study has shown that 14.3% of women aged 18-25 with one lifetime sex partner, 22.3% with 2 lifetime partners and 31% with more than 3 lifetime partners had HPV infection.2 A 2002 National Survey in the United States revealed that 40% of females in the U.S. were sexually active by age 16 and 70% by age 18.3 The majority of HPV infections are transient and asymptomatic and cause no clinical problems; 70% of new HPV infection clears within one year. Persistent infection with high- risk cancer-inducing types is one consequence of infection that vaccination may prevent.
The longest follow-up of the phase II trial of women vaccinated has been 5 years and reveals that antibody titers plateau by about 24 months but there is no evidence of waning efficacy in preventing cervical cancers at this point, ie, 95.8% efficacy (CI 83.8-99.5%) Follow-up studies by Merck to determine boosting intervals in the 5,500 women enrolled will be continued for at least 14 years by following Pap testing results and serologic testing linked to vaccine and cancer registries. Adverse effects to vaccination were mostly local pain, with reporting of fever in less than 5.0%. There were no reports of anaphylaxis. In the future, Cervarix® a GlaxoSmithKline HPV vaccine submitted to the FDA and pending approval has a different adjuvant and may require less boosting.
Wynia at the AMA has written an interesting article on how public health and public trust were affected by an aggressive stance and lobbying effort by Merck with release of Gardasil®.4 His opinion is that a Merck donation of funds to Texas Governor Rick Perry, at the time of his state law mandating vaccination, was inappropriate and self-defeating. He contended that public health decisions should be delegated to the public health community, and public trust relies on a clear separation between those making money on vaccines and those making decisions about which vaccines to require or recommend.
The backlash against the Merck campaign will have seriously held back effective HPV vaccination should religious conservatives partner with patient advocacy groups and vaccine phobics to question how vaccines are required prior to school entry. Wynia ends by describing the lesson learned from this story: public trust relies upon the public health community making unbiased and fully disclosed decisions without lobbying or market pressures. For this associate editor and commentator, the take-home message from this event is that pharmaceutical companies should not be allowed to influence government in such public health decisions through either funding or lobbying.