LOS ANGELES—Vaccines designed to protect against human papillomavirus (HPV)—and thus protect against cervical cancer—are showing sustained protection at 5 years, according to long-term data for Merck's FDA-approved vaccine, Gardasil, and the GlaxoSmithKline AS04 candidate vaccine presented at the 2007American Association of Cancer Research Annual Meeting (abstracts LB-187 and 4900).
Gardasil, a quadrivalent vaccine designed to protect against HPV types 16, 18, 6, and 11, was shown to provide nearly 100% protection against cervical intraepithelial neoplasia (CIN) 2/3 and adenocarcinoma in situ caused by HPV types 16 and 18 at a follow-up time of 3 or more years after inoculation, reported Darron Brown, MD, professor of medicine, microbiology and immunology, Indiana University School of Medicine, Indianapolis.
Gardasil targets the HPV types responsible for the majority of clinical HPV disease, Dr. Brown said. Types 16/18 are responsible for 70% of cases of cervical cancer, anal/genital cancer, and vulvar and vaginal neoplasia, and 25% of CIN 1. Types 6/11 are responsible for 90% of cases of genital warts and recurrent respiratory papillomatosis, and 10% to 15% of CIN 1. Males are carriers for all four HPV types.
Dr. Brown's report encompassed 3 to 5 years of follow-up of the Gardasil trials. In the combined database of more than 20,000 patients, there has been only one case of CIN 2/3 related to HPV types 16/18 or 6/11. "The one patient who developed CIN 3 had HPV type 52, a cousin of HPV 16, upon enrollment, and she had an abnormal Pap smear at 28 months," he said. "Her biopsy was positive for both HPV 52 and 16, but in a second specimen obtained during the LEEP procedure, only HPV 52 was demonstrated. Whether this was a laboratory error or she was contaminated with HPV 16 is hard to say. She was counted as a positive case."
In an analysis of the general study population of randomized subjects who received at least one dose—which included subjects with pre-existing infection with one of the four HPV types, protocol violators, and subjects with fewer than three doses—efficacy was 44%, which is "still a considerable degree of efficacy," he said. Almost all cases in the vaccine arm occurred in women with prior infection with HPV 16/18. Efficacy against all high-grade disease (due to vaccine and also nonvaccine types) was 18%. "This shows that HPV is already a prevalent infection in this age group," Dr. Brown commented. "We need to vaccinate before there is a chance of infection."
The cross-protective effect of Gardasil against other HPV types is currently being studied. Preliminary studies show that antibodies triggered by the vaccine neutralized HPV types 31 and 45 as well, which are genetically related. "This is important since 30% of cervical cancer is caused by types other than HPV 16/18," Dr. Brown noted.GSK Candidate Vaccine
Investigators reported the same high degree of sustained efficacy with the GSK candidate vaccine AS04. The vaccine also provided significant cross-protection for HPV types 45 and 31, reported Stanley Gall, MD, professor of obstetrics, gynecology, and women's health, and of public health and information sciences, University of Louisville, Kentucky.
