October 01, 2014
By Will Boggs MD
NEW YORK - In a phase III trial, the bivalent human papillomavirus (HPV) 16/18 vaccine protected women over age 25 from HPV infection and cervical abnormalities related not just to the vaccine types but also to HPV types 31 and 45.
"We were pleased but not surprised to see high vaccine efficacy against HPV 16 and 18 six-month persistent infections in women over 25 years," Dr. S. Rachel Skinner from the University of Sydney, Westmead, New South Wales, Australia told Reuters Health by email. "This was the case for women in our according-to-protocol (ATP) cohort, who did not have evidence of prior exposure to these types. We were however, surprised to see moderately high vaccine efficacy against both HPV 31 and 45, two other important causes of cervical cancer worldwide."
The main population for prophylactic HPV vaccination is adolescent girls who have not yet been exposed to the virus, but HPV vaccines are licensed for use in some countries for women up to age 45. The quadrivalent HPV 6/11/16/18 has already been proven efficacious in women aged 24 to 45 years.
In the VIVIANE study, Dr. Skinner and colleagues tested the HPV 16/18 vaccine in 5752 women older than 25 (2881 assigned to vaccine, 2871 controls). The trial is ongoing and is planned to last for seven years.
The primary endpoint was vaccine efficacy against a combined endpoint of six-month persistent infection with HPV 16 or HPV 18 or CIN grade 1 or greater associated with HPV 16/18.
The vaccine was 81.1% effective for the combined primary endpoint and 82.9% effective for six-month persistent infection with HPV 16/18, the researchers reported September 2nd online in The Lancet.
The vaccine was effective in women in the ATP cohort for efficacy who were seropositive and DNA-negative for HPV 16 or HPV 18 or both at baseline.
In stratified analyses, the vaccine was effective against six-month persistent infection in women aged 26 to 35 or 36 to 45. Moreover, the researchers report significant vaccine efficacy against ASC-US+ associated with HPV 16/18 in all cohorts, including those with previous HPV infection or disease. There was also significant cross-protection against HPV 31 and HPV 45.
The overall vaccine efficacy for protection against CIN1+, regardless of HPV DNA status, was 14.9%. Among women who were DNA-negative at baseline, however, its efficacy was 91.1%.
All initially seronegative women seroconverted for HPV 16 and HPV 18 by month seven (one month after the third dose).
Injection site symptoms were more common in the vaccine group than in the control group, but overall there was no difference between the groups in adverse events.
"At this stage, we do not recommend vaccination of all women over 25 years, en mass, as public monies should be targeted to achieving high uptake in the younger age group, in particular young adolescents, where maximal public health benefit can be achieved," Dr. Skinner said. "However, should an individual woman over 25 years who may have missed out on mass vaccination, seek the vaccine through her doctor, we recommend vaccination. We believe she has a reasonable chance of benefit."
"The chance of benefit will be greater the younger the woman: women aged 26-35 will obtain greater benefit than women over 40, for example," Dr. Skinner said. "We did not see evidence of vaccine benefit to women over 45 years."
"There is no reason to withhold vaccine from women who request it," Dr. Skinner said. "This is so for women regardless of whether they have a history of HPV infection or disease. Any existing lesions should be treated of course, but vaccination may also be given, as they will prevent infection or reinfection with HPV 16 and or 18 in the future."
She added, "We do not think that women should be screened for HPV DNA prior to vaccination. Evidence of current infection with HPV does not preclude benefit from vaccination. Any test for HPV is unlikely to be specific for vaccine types, and in any case, infection with both types is very unlikely."
Dr. Philip E. Castle from the Global Coalition Against Cervical Cancer in Arlington, Virginia, who coauthored an editorial with Dr. Kathleen M. Schmeler from the University of Texas MD Anderson Cancer Center in Houston, told Reuters Health by email, "There are now multiple studies with both HPV vaccines in younger (
Dr. Castle added, "There have been unfortunate rumors and unsubstantiated public comments about the safety of HPV vaccination. The World Health Organization's Global Advisory Committee on Vaccine Safety stated on March 12, 2014, 'We continue to closely monitor the safety of HPV vaccines and, based on a careful examination of the available evidence, continue to affirm that its benefit-risk profile remains favorable. The Committee is concerned, however, by the claims of harm that are being raised on the basis of anecdotal observations and reports in the absence of biological or epidemiological substantiation.'"
Dr. Hugo C. Turner from Imperial College London, London, UK recently investigated the cost-effectiveness of HPV vaccine in women previously exposed to HPV. He told Reuters Health, "These results provide important insights regarding how the HPV 16/18 vaccine is efficacious in women older than 25, and support previous findings in suggesting that it is effective for women who are currently not infected, irrespective of their history of exposure. This has important implications for clinicians and the public in making informed recommendations and decisions."
GlaxoSmithKline Biologicals SA funded the VIVIANE trial, employed seven of the 28 authors named on the report, and provided funding for all investigators at the clinical study sites through their institutions.
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