2 HPV vaccines, 7 questions that you need answered
The availability of two vaccines against human papillomavirus raises numerous questions about fine points of cervical cancer prevention
IN THIS ARTICLE
Dr. Harper: A smart clinician would ask the patient what she values. The physician is obligated to present the evidence and let her choose!
Dr. Lonky: What does the evidence suggest?
Dr. Felix: A clear recommendation between Cervarix and Gardasil is very difficult to make at this time, for the reasons already stated. Both vaccines provide 98% protection against HPV 16 and 18 for the prevention of CIN 2+ lesions.3,9 As we have discussed, both vaccines also provide protection against high-risk strains of HPV other than types 16 and 18.
In the Cervarix trial, there was an overall reduction of all CIN 2+ lesions that was higher as a percentage of total lesions than the reduction seen in the Gardasil trial.3,9 However, unlike Cervarix, Gardasil significantly reduced the rate of vaginal intraepithelial neoplasia (VaIN) and vulvar intraepithelial neoplasia (VIN).9
Dr. Harper: GlaxoSmithKline is analyzing its data on vulvar and vaginal protection, and it is likely that Cervarix will demonstrate some efficacy in this regard, too. But the economic burden of noncervical cancers is estimated to be only 8% of the economic burden of all HPV-related diseases.20 The prevention of cervical cancer is the dominant clinical and economic force for vaccination.
Dr. Felix: Clearly, the protection against genital warts demonstrated in the Gardasil trial will not be realized with Cervarix, as it does not offer immunization or cross-protection against HPV 6 or 11. Gardasil’s protection against HPV 6 and 11 prompted FDA approval of the vaccine for boys and men.21
According to the WHO, when counseling girls and women about the HPV vaccine, the clinician should weigh the possible value of a deep reduction in total CIN 2+ lesions provided by Cervarix against the reduction in VaIN, VIN, and genital warts provided by Gardasil.15 Boys and men will see clinically proven benefits only from Gardasil for the prevention of external genital warts. Other benefits are strictly theoretical.22,23
Dr. Harper: Vaccine protection must last at least 15 years to reduce the rate of cervical cancer. Otherwise, the development of cervical cancer will only be postponed, if boosters are not implemented.
It is now widely recognized that Cervarix induces high antibody titers, offering 100% efficacy even after 8.4 years, making it very likely that the protection it provides will continue for at least 15 years. It is also widely acknowledged by immunologists that Gardasil-induced titers for HPV 6, 11, and 18 are much shorter-lived, so protection is likely to wane 5 to 10 years after vaccination.
That means that Gardasil provides excellent protection against one cancer-causing type of HPV. In addition, it protects against genital warts caused by HPV types 6 and 11 for at least 5 years. In comparison, Cervarix protects against five cancer-causing types of HPV, thereby preventing about 90% of cervical cancers, and is likely to remain effective for at least 15 years.
There are 10 times as many women who have an abnormal Pap test as there are women who have genital warts, so one would think that Cervarix would be the vaccine of choice in preventing the life-threatening disease of cervical cancer.
Dr. Smith-McCune: I would agree that the choice should be discussed with patients—and with parents. If the objective is primarily to protect against cervical cancer precursors, then the bivalent vaccine may be the better choice, with the caveat that we can’t really compare the results from the vaccine trials for reasons discussed earlier, and there are no data from a randomized head-to-head trial comparing the two vaccines. If the decision involves a desire to reduce genital warts or vulvar and vaginal dysplasia, then the quadrivalent vaccine would be the better choice.
6. What impact do the vaccines have on screening?
Dr. Lonky: Do the vaccines have varying effects on our need to screen for, triage, and treat cervical cancer precursors?
Dr. Harper: The Pap smear has reduced the rate of cervical cancer in the United States by 75%—that rate is now at an all-time low of 8 cases for every 100,000 women. But the Pap smear is not perfect; there is a 30% false-negative rate among women who develop cervical cancer, and a large false-positive rate that involves referral to colposcopy for minimally abnormal cytology reports. And when CIN 2+ disease is detected, treatment is not without risk. Surgery increases the risk of reproductive morbidity in future pregnancies. Having protection against this outcome could be tremendously valuable for some women.
Compare the HPV vaccine, which has probable benefit but also the potential for serious adverse events, including demyelinating diseases that cause blindness, paralysis, and death in a small number of recipients.
