Cervarix Provides Long Duration of Protection Against HPV 16 and 18

Roxanne Nelson

December 03, 2009

December 3, 2009 — The Cervarix vaccine, manufactured by GlaxoSmithKline, provides a high level of long-term protection against human papillomavirus (HPV) types 16 and 18. According to new data published online December 3 in The Lancet, the HPV 16/18 AS04-adjuvanted vaccine offered sustained protection and long-term efficacy for up to 6.4 years.

The researchers found that the vaccine was 95.3% effective against incident infection with HPV 16/18, and was 100% effective against 12-month persistent infection. Effectiveness against cervical intraepithelial neoplasia grade 2 and above (CIN2+) was 100% for lesions associated with HPV 16/18 and 71.9% for lesions independent of HPV.

They also noted that during months 63 to 76, antibody concentrations against HPV 16 and HPV 18 were at least 13 and 12 times higher, respectively, than concentrations recorded after clearance of a natural infection, as demonstrated in a previous study (Lancet. 2007;369:2161-2217).

How long immunogenicity will last is a very important question that our paper partially answers, explained study author Barbara Romanowski, MD, a clinical professor in the Division of Infectious Diseases at the University of Alberta in Edmonton. "Our results demonstrate that antibody levels are excellent after 6.4 years of follow-up, and a subset of these women will continue to be followed for at least 9.5 years," she told Medscape Oncology.

"Mathematical modeling suggests that the antibody levels might last at least 20 years, but this will have to be borne out with long-term follow-up studies," she added. "The key message of this study is that the bivalent HPV vaccine has high efficacy against HPV 16 and 18, and provides cross protection against other high-risk HPV strains. The vaccine is highly immunogenic and safe.

The US Food and Drug Administration approved Cervarix in October 2009 for use in the prevention of cervical cancer and precancerous lesions caused by HPV 16 and 18 in women 10 to 25 years of age. It has been commercially available in the European Union and other nations since 2007.

As previously reported by Medscape Oncology, large clinical trials found the vaccine to be 93% effective in preventing CIN2+ associated with HPV 16 and 18.

Affordability and Long Duration Needed for Poor Nations

The evidence from large phase 3 trials suggests that vaccinating girls before they reach adolescence against HPV 16 and 18 would be cost-effective in preventing cervical cancer in even the poorest countries, provided the cost of vaccination falls to US$10, writes Gary M Clifford, PhD, from the International Agency for Research on Cancer in Lyon, France, in an accompanying editorial.

However, he notes, "the greatest source of uncertainty with respect to the potential effect of HPV vaccines remains the duration of the immune response. If vaccine boosters are needed later, the complexity of program delivery, particularly in low-resource countries, increases considerably."

The GAVI Alliance, a global health partnership between the private and public sectors that subsidizes vaccines for the poorest nations, is currently reviewing HPV vaccine as a candidate for sustainable financing, he writes, but eligible countries will need to obtain the maximum benefit for every dose of HPV vaccine administered.

The target age for the vaccine is a balancing act — early enough to catch girls before sexual debut but late enough to provide an as-yet-unknown duration of immunity that will offer protection for as long as possible, writes Dr. Clifford.

The results of the current trial suggest that this window of protection is at least 6 years, he notes, adding that it "leads us to strongly suspect that, as these and other vaccinated women are followed up, the period of protection might be much longer."

Follow-Up Shows High Efficacy, Long Duration of Immune Response

The study was conducted by the GlaxoSmithKline Vaccine HPV-007 Study Group, and is an extended follow-up of an efficacy trial that began in 2001. The initial study examined 1113 women between the ages of 15 and 25 years (560 in the vaccine group and 553 in the placebo group). All participants had normal cervical cytology and were HPV 16/18 seronegative and oncogenic HPV DNA-negative (14 types) at initial screening.

The follow-up study took place at 27 sites in 3 countries between November 10, 2003 and August 9, 2007. Of the 1113 women in the initial study, 776 continued in the follow-up study, and 700 (90%) completed the study. Cervical samples were tested every 6 months for HPV DNA, primarily to assess the long-term effectiveness of the vaccine in the prevention of incident cervical infection with HPV 16, HPV 18, or both.

The researchers observed that high vaccine efficacy was achieved against any cytologic abnormal change of atypical squamous cells of undetermined significance or greater, or against low-grade squamous intraepithelial lesions or greater that were associated with HPV 16, HPV 18, or both.

The vaccine was 100% effective for both CIN1+ and CIN2+ associated with HPV 16, HPV 18, or both. None of the vaccine recipients had a CIN event during the 6.4 years of follow-up, and all new cases of CIN2+ that were identified during the follow-up period occurred in the placebo group.

An analysis of cytohistologic end points independent of HPV DNA in the lesion showed that there was an efficacy rate of 35.4% against any cytologic abnormal changes of atypical squamous cells of undetermined significance or greater, and an efficacy rate of 39.4% for low-grade squamous intraepithelial lesions or greater. They also noted that the vaccine was highly effective against any CIN1+ and CIN2+, and nearly all recipients (99%) remained seropositive for anti-HPV 16 and anti-HPV 18 total immunoglobulin G antibodies.

Safety profiles were similar between the vaccine and placebo groups. In the vaccine group, 30 women (8%) reported a serious adverse event, as did 37 women (10%) in the placebo group. None of the serious adverse events that were reported were judged to be related or possibly related to vaccination, the authors note, and there were no deaths.

The study was funded by GlaxoSmithKline Biologicals (Belgium). A number of study authors have disclosed relevant financial relationships; these are detailed in the paper.

Lancet. Published online December 3, 2009.


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