Currently Approved Prophylactic HPV Vaccines

Diane M Harper

Disclosures

Expert Rev Vaccines. 2009;8(12):1663-1679. 

In This Article

Expert Commentary

The HPV vaccines neutralize type-specific HPV infections prior to engulfment into the basal cells of the epithelium. Therefore, the vaccines should provide benefit to any epithelium that is at risk for HPV infection, with cervical cancer being the most prevalent HPV-associated cancer. Other cancers less closely associated with HPV occur in the vagina, vulva, penis, anus and oropharynx.[7] Results from the HPV vaccine trials to prevent CIN and cervical cancer should theoretically translate into some level of partial protection from these other HPV-associated cancers. Specific long-term cancer registries or ecologic epidemiological data will be needed to determine the extent of impact, potentially quite small, of the HPV vaccines on these cancers several decades from now.

Likewise, the benefit of Gardasil for the prevention of the noncancerous but lethal juvenile respiratory papillomatosis, caused at minimum by HPV-6 and -11, will require decades of follow-up to ascertain whether efficacy occurs and whether the duration of vaccine efficacy truly prevents this disease or merely prolongs the number and frequency of surgeries with no difference in overall survival. To prevent this disease, the prophylactic vaccines will have to prevent the autoinoculation from the original field infection to prevent further disease. The long-term impact on genital wart prevention could prevent some nonlethal HPV infections. The disutility of genital warts is the replacement of a normally functioning protective epithelium with warty tissue that can be both disfiguring and highly disruptive to normal life activities. Serious doubts about Gardasil's long-term protection are raised by the surprisingly lower efficacy in preventing genital warts of any HPV type, and the rapid fall in antibody titers that do not respond uniformly well to the anamnestic challenge.

Vaccination of 12–15-year-old girls has certainly been shown by cost–effectiveness models to have the potential to reduce cervical cancer incidence many decades in the future.[38–43] The scientific evidence supporting this program is the immunobridging principle and the generally good safety profile, with only rare debilitating neurologic adverse events reported. Despite no efficacy data and no evidence for duration of efficacy past the first decade, public-health bodies recommend young adolescent female vaccination. Should the duration be less than 15 years, cervical cancers will only be postponed at a great cost, not prevented. In addition, there has been very limited public acceptance of vaccinating 10–12-year-olds, with the greatest proportion of vaccinees being 16–20 years of age.[55,69]

But there are millions of women under 26 years of age who are already sexually active and who may derive immediate benefit from vaccination based on induced antibody titers that exceed the bridging titers induced in adolescents. HPV vaccines cannot stop the progression of HPV disease outcomes in cells already infected with HPV, but induced antibodies should be able to neutralize autoinfecting HPV virions from the original field infection, thereby disrupting the infectious cycle and preventing the recurrence of CIN and anogenital cancers that currently occurs at frequencies up to 12-times the general population rate of disease and as long as 20 years out from the original infection.[26,70–72]

In industrialized countries with organized screening, regardless of whether you choose to vaccinate or which vaccine you choose to use for vaccination, the most important message to relay to women is the continued need for cervical cancer screening exams. The vaccines do not replace Pap testing. The incidence of cervical cancer will increase if screening is forgotten after vaccination. The decision to vaccinate in countries with organized, well-attended screening programs must be made by the individual herself or as a shared decision with her provider. Furthermore, the benefits of reducing the number of abnormal Pap screens, the number of colposcopies and the number of excisional treatments necessary must be weighed against the risks of missing screening exams, booster needs and small but real serious side effects, including death. The incidence of cervical cancer will not be reduced by vaccination alone or vaccination in combination with screening (Figure 5).

Figure 5.

Maximal potential effect of screening, vaccination, both or neither on the incidence of cervical cancer in the USA. The lowest incidence Pap screening can achieve in the nonvaccinated population is two to three per 100,000.[76] Currently, in the USA, the Pap screening program identifies on average seven per 100,000 new women with cervical cancer every year.[108] Without any screening or vaccination, the yearly incidence rate of cervical cancer will quickly approach 50 per 100,000.[77] Assuming 100% vaccine coverage, and lifetime efficacy, the incidence of cervical cancer will be higher (in the case of Gardasil®, twice as high) than the rate currently achieved by screening only if vaccinated women cease their Pap screening. Screening and vaccination will not reduce the incidence of cervical cancer by any measurable degree,[78] but will provide reassurance to lengthen the screening interval.
*Data from [108].Data from [78].
§Data from [77].

In countries without well-attended, organized screening, the lasting effects of HPV vaccination will be completely dependent on the duration of vaccine efficacy and the population coverage achieved, with the potential to save hundreds of thousands of women's lives, balanced against the very small risk of serious adverse events.

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....