Two Cervical Cancer Vaccines

1. Two prophylactic HPV vaccines, Cervarix™ (GlaxoSmithKline) and Gardasil™ (Merck) have been licensed for use. Both have been tested in large randomised placebo-controlled trials involving thousands of women from different countries across the world.
2. Impressive protection against persistent vaccine-specific HPV infection has been demonstrated over short- to medium-term follow-up periods. Long-term follow-up data are still required to answer the question of longevity of immune protection and whether booster vaccination(s) will be necessary, and at what time interval.
3. Because of ethical and consent issues, efficacy cannot be determined among pre-adolescent girls, but is assumed by extrapolating data from the young women involved in the original vaccination trials. These suggest higher immune responses following vaccination among young adolescent girls (and boys) when compared with young adults, suggesting that vaccination at this younger age may result either in longer sustained immunity, improved long-term clinical efficacy, or both.
4. It is difficult to assess the impact of an immunisation strategy when many factors are still unknown. 
5. The coverage for the third dose is critical as the vaccine is locally painful and girls may be reluctant to complete the course.
6. The vaccines remain prohibitively expensive - universal HPV vaccination is unlikely in resource-poor countries lacking organised screening programmes, where cervical cancer remains a major cause of cancer-related death in women, and vaccination would be most beneficial. Those countries providing HPV vaccination at the moment have more efficient cervical screening programmes and lower cervical cancer rates than those yet to introduce it.
7. Merck was the first of two pharmaceutical companies to license its vaccine in October 2006, giving it a commercial head start. This quadrivalent vaccine confers immunity against the two oncogenic strains of HPV responsible for 70% of cervical cancers (HPV 16 and 18), as well as two strains that together cause 90% of genital warts (HPV 6 and 11). To many, a vaccine that protects against four strains has appeared to be inherently ‘better’ than one protecting against two strains.15 The bivalent vaccine Cervarix did not become available until almost a year later, in September 2007. Cervarix protects against HPV types 16 and 18, but does not prevent genital warts.
8. Insofar as Cervarix does not prevent genital warts, its use may amount to a ‘missed opportunity’. Genital warts are a very common sexually transmitted viral infection responsible for unsightly lesions that are both difficult and costly to treat. Women with genital warts also risk spread of the infection to the respiratory tract of their newborn infant during childbirth. Recurrent respiratory papillomatosis is a rare, but chronic, debilitating disease characterised by hoarseness, stridor and respiratory distress in the newborn, and requires lifelong repeated surgical intervention and prolonged hospital stays, even causing death in a minority of cases.
9. Published data do not distinguish either vaccine as superior in terms of clinical effectiveness or toxicity. However, recent data released by GlaxoSmithKline from their head-to-head comparison of the two vaccines reported that Cervarix induced significantly higher HPV 16 and 18 serum neutralising antibody titres, as well as higher levels of neutralising antibodies in cervicovaginal secretions and circulating HPV 16 and 18-specific memory B-cells. These results would suggest that a longer duration of protection against HPV infection may be conferred by Cervarix. Declining antibody levels post-vaccination may not, however, indicate a loss of protection, as immunological memory may persist at low levels, and is difficult to measure. Natural viral challenge may be sufficient to ‘boost’ declining serological responses, although booster vaccination is superior.
10. Future cervical screening. Cervical cancer develops after an infection period of a decade or more, and up to 30% of cervical cancers are caused by HPV types not included in either vaccine. Although some degree of cross-protection against similar high-risk HPV types has been presumed from trial data, vaccinated women are still clearly at risk of contracting other oncogenic HPV types that can cause cervical cancer, and cervical screening will still be necessary, even for vaccinated women.
11. Safety scares. In general, both Cervarix and Gardasil appear to be safe and well tolerated. Injection site adverse events, including pain, swelling and redness, have been reported more frequently by women receiving the vaccine, compared with those receiving placebo in clinical trials. Cervarix is recognised to be a more painful inoculation than Gardasil, but even so, most side effects disappear within the first day or two.
12. There have been no deaths attributable to either vaccine in any of the clinical trials to date. Pregnancy and congenital anomaly data have been reported for Gardasil, but not for Cervarix. Higher rates of congenital anomalies unrelated to type have been observed.
13. Maintaining high vaccine coverage. Interim results for the uptake of the third dose has shown a drop in coverage from 83% at the first dose to 74% for dose 3. Whether girls who receive only the first two doses of the vaccine will show sufficient immunity against HPV to prevent subsequent infection remains unclear.
14. The effect of mistimed doses is not fully understood. Data from hepatitis B vaccination studies suggest that longer intervals between second and third doses of the HPV vaccine may not be detrimental to the strength of the immunity generated, presumably as long as HPV exposure does not occur during the delay.