CALGARY, ALTA. — As an epidemiologist whose research focuses on the prevention of cervical cancer, Dr. Eduardo L. Franco spends a lot of his time dispelling arguments and protests from other health care professionals and patients that more research is needed before universal human papillomavirus vaccination can be recommended worldwide.
“Although clinical experience has just passed 6 years, the evidence base is one of the strongest in disease prevention,” Dr. Franco said at the annual meeting of the Society of Obstetricians and Gynaecologists of Canada. “The standard of proof is far more rigorous than that used in evaluation of candidate vaccines of the past. It may be the most scrutinized vaccine by the public and the media concerning need and safety.”
Prophylactic HPV vaccines include a quadrivalent form made by Merck & Co. that was licensed in the United States in June 2006 and a bivalent form made by GlaxoSmithKline that was submitted to the FDA in March 2007.
Dr. Franco, director of the division of cancer epidemiology at McGill University, Montreal, shared several examples of arguments against HPV vaccination that he encounters, followed by his counterargument for each.
One chief argument he hears is that the vaccine is too costly and unaffordable where it's most needed. However, he said, procurement programs such as the CDC's Vaccines for Children Program, the Global Alliance for Vaccines and Immunization, and the Pan American Health Organization's revolving fund should help to lower the cost. “Historically,” he added, “prices decline with time since deployment.”
Other common arguments against HPV vaccination include the following:
▸ There are no data on long-term duration of protection. In fact, to date, studies demonstrate a sustained antibody response with no indication that humoral immunity will wane before 10 years. “Even with lowered antibody titres, postvaccination protection has continued unabated,” said Dr. Franco, who also is a professor of epidemiology and oncology at McGill. “We did not wait for such proof before deploying other vaccines.”
▸ Protection is limited; vaccines cover only two oncogenic types. In fact, protection is against the two most important types (HPV 16 and 18), which translates into a protective fraction of 70% of all cervical cancers. That protection “is likely to be expanded via cross-protection,” he said. “In combination with tailored screening strategies, it may achieve unprecedented lifelong protection.”
▸ Screening will continue to be needed. True, Dr. Franco said, but recent progress on new technologies such as HPV testing with Pap triage “will permit extending screening intervals safely and cost effectively. Proper integration of primary and secondary prevention strategies is likely to reduce costs and improve cervical cancer control.”
▸ There is a risk of type replacement, which occurred with the pneumococcal vaccine. In fact, Dr. Franco said, type replacement is unlikely to occur because there is no epidemiologic proof that HPV types compete for specific niches. “Several studies have tested this hypothesis,” he noted. “The fraction of the population not exposed to HPV 16 or 18 is always high; exposure to HPV 16 or 18 does not constrain the pool of susceptible individuals who could acquire other HPVs.”
▸ We should not vaccinate preteens and teens; there are no efficacy data on patients aged 9-14 years. This age group is not at risk for lesions and monitoring them “would be unethical and unproductive,” Dr. Franco said. “Immunobridging” studies show that vaccine-induced humoral response in preteens is the highest among all groups, “which is sufficient justification for expectation of benefit,” he said.
▸ There is no proof yet that vaccination can reduce the risk of invasive cancers. Dr. Franco counters this notion by pointing out that absence of evidence is not evidence of absence. “Sensible judgment based on understanding of the natural history of HPV infection and cervical cancer indicates that prevention of precancerous lesions is an acceptable end point,” he explained.
▸ There is no cervical cancer epidemic. Dr. Franco asserts that the health costs, morbidity, and mortality associated with cervical cancer are sufficiently important to justify action and that the HPV vaccination is likely to exert protection against other neoplastic diseases such as oropharyngeal cancer and benign genital warts.
▸ More research is needed on safety. Dr. Franco responds to this argument by noting that the safety data on the HPV vaccine “are among the most well documented for any new vaccine. There was no waiting period for the adoption of other vaccines with lesser standards of proof. Inaction has a high cost in terms of morbidity and mortality that could have been averted.”