So here is the study that has caused everyone to talk about this. It has a list of what I think are the conclusions/takeaways at the end if you just want to skip to that.
Both the quadrivalent and bivalent human papillomavirus (HPV
) vaccines are highly effective in preventing cervical intraepithelial neoplasia grade II to III or adenocarcinoma in situ in women not infected with the relevant HPV
type before vaccination. However, the effect of the HPV
quadrivalent vaccine on disease progression and future risk for disease in women with precancer or cervical disease is not known.
This study involves women who have been vaccinated with the quadrivalent HPV
vaccine and who have received cervical surgery or have been diagnosed with genital warts or vulvar disease. The study authors examined the effect of the vaccine on disease progression and future risk for HPV
STUDY SYNOPSIS AND PERSPECTIVEHPV
vaccination substantially reduced the risk for subsequent HPV
disease in women who already had 1 bout of HPV
-related disease, according to a study published online March 27 in BMJ.
"These are, to our knowledge, the first results in vaccinated women who have undergone treatment for HPV
-related disease," write the authors, headed by Elmar Joura, MD, from the Medical University of Vienna in Austria.
The data come from a subgroup of women who participated in trials of the quadrivalent HPV
vaccine Gardasil (Merck & Co).
Women who had HPV
infection at the time of vaccination and who developed cervical, vulvar, or vaginal HPV
disease had a substantially reduced risk of developing subsequent HPV
-related disease after the first definitive treatment.HPV
vaccination substantially reduced the risk for subsequent HPV
disease — not only that caused by the 4 viral strains in the quadrivalent vaccine (HPV
subtypes 6, 11, 16, and 18), but also that caused by other strains of HPV
This study "reinforces much of what we already know about the protective properties of the quadrivalent vaccine, including cross-protection against nonvaccine HPV
types and vaccine benefit despite HPV
exposure," writes Jane Kim, assistant professor of health decision science at Harvard School of Public Health, Boston, Massachusetts, in an accompanying editorial.
Subgroup of Women
The study analyzed data collected from 2 large company-sponsored placebo-controlled trials of Gardasil, known as FUTURE I and FUTURE II. Together, they involved 17,622 women 15 to 26 years of age who were randomized to receive 3 doses of the quadrivalent HPV
vaccine or placebo. They were subsequently followed for approximately 4 years.
The analysis focused on a subgroup of 2054 women who participated in these trials and who were subsequently treated for cervical, vulval, or vaginal disease.
More than half of this subgroup (1350 women) underwent cervical surgery (which included any method used to treat cervical disease) — 763 from the placebo group and 587 from the vaccine group.
The researchers calculate that the incidence of any subsequent HPV
-related disease in the cervix was 6.6 in the vaccine group and 12.2 in the placebo group — a reduction of 46.2% with vaccination.
When only high-grade disease of the cervix was considered, this reduction is even greater; vaccination reduced the risk for any subsequent high-grade disease of the cervix by 64.9%.
The remaining women in the subgroup (229 in the vaccine group and 475 in the placebo group) were subsequently diagnosed with either genital warts or vulvar or vaginal intraepithelial neoplasia. Here, the incidence of any subsequent HPV
-related disease was 20.1 in the vaccine group and 31.0 in the placebo group — a reduction of 35.2% with vaccination.
This was primarily driven by a reduction in the incidence of genital warts (63% reduction after vaccination), the authors note.
In all cases, the reduction was for all subtypes of HPV
-related disease, including strains of HPV
virus that were not included in the vaccine.
New Findings Welcome
These findings are "welcome," Dr. Kim writes.
This study "moves us closer to understanding the full scope of benefits from HPV
vaccination by showing for the first time that vaccine protection against disease can endure beyond the management of HPV
-related disease in women already vaccinated," she adds.
However, Dr. Kim takes issue with some of the conclusions drawn by the authors.
This study corroborates previous findings that the benefits of vaccination are not limited to the primary target group of young sexually naïve girls, Dr. Kim explains. The findings highlight the importance of vaccinating at an early age, when exposure to HPV
is minimal, to maximize protection against all HPV
types targeted by the vaccine.
Most important, she adds, this study examines a unique subgroup of women who were vaccinated before their first treatment for HPV
-related disease. The authors suggest that these results could be generalized to women who are considering HPV
vaccination after treatment for HPV
-related disease, but Dr. Kim disagrees, and suggests that more data are needed.
"Only surveillance of vaccinated populations in the real world can provide clear evidence of the effectiveness of the vaccine in women who have been treated before vaccination," Dr. Kim writes. "As we await this information, it is important to emphasize to providers and decision makers that generalizations of study findings are premature."
The study was funded by Merck & Co. Dr. Joura reports receiving advisory board fees from Merck; and lecture fees from Merck, Sanofi Pasteur MSD, and GlaxoSmithKline. Several coauthors are employees of Merck & Co, and several report receiving funding from Merck and GlaxoSmithKline for HPV
vaccine studies, and from other pharmaceutical companies. Dr. Kim has disclosed no relevant financial relationships.
BMJ. Published online March 27, 2012. Abstract, Editorial
This is a retrospective cohort study of women in the FUTURE I and FUTURE II trials — randomized, double-blind, placebo-controlled trials testing the efficacy of the HPV
quadrivalent vaccine covered HPV
types 6, 11, 16, and 18.
Included in this study were women who were not pregnant, who had a lifetime number of no more than 4 sexual partners, and who had undergone either cervical surgery or were diagnosed with cervical or vulvar disease.
The studies did not include baseline HPV
testing or clinical examination before randomization, so women with ongoing HPV
disease were permitted.
Women were randomly assigned to receive either 3 doses of quadrivalent HPV
vaccine or placebo at day 1, month 2, and month 6.
Cytology specimens were classified using the Bethesda System 2001, using ThinPrep (Cytyc; Boston, Massachusetts).
All participants were required to use contraception and were tested for pregnancy before each vaccine administration.
The outcome was the average time from diagnosis of disease to treatment of genital warts or vulvar or vaginal intraepithelial neoplasia.
The 2 trials collectively diagnosed and treated 17,622 women.
1350 women qualified for the cervical surgery, and 704 for the second (diagnosis of vulvar or vaginal disease) analysis.
Mean age was 19.7 years, two thirds were white, and from 12.9% to 21.4% were Hispanic.
More placebo recipients (n = 763) than vaccine recipients (n = 587) underwent cervical surgery for disease because of any HPV
Among women who underwent cervical surgery, more of those in the vaccine group had higher prevalence of squamous intraepithelial lesions at baseline and a higher prevalence of HPV
DNA compared with placebo.
Placebo recipients were at increased risk for developing HPV
Within 1.3 years after the vaccination, the incidence of any subsequent disease among placebo recipients was 12.2 per 100 person-years at risk, and 5.2% developed subsequent high-grade cervical, vulvar, or vaginal disease.
Compared with those who underwent surgery, those with genital warts or vulvar or vaginal intraepithelial disease were 3 times more likely to develop HPV
During a mean of 1.2 years of follow-up, 13.0% of those with initial vulvar or vaginal disease developed high-grade cervical, vulvar, or vaginal disease.
Vaccination with the quadrivalent HPV
vaccine was associated with significant reduction in risk for any subsequent HPV
-related disease in women who underwent cervical surgery, irrespective of causal HPV
The risk reduction was 46.2% overall.
The risk reduction was 48.3% for any cervical disease, 64.9% for any high-grade cervical disease, and 63.0% for genital warts.
Vaccination was also associated with a significant reduction (79.1%) in any subsequent disease related to vaccine HPV
types and with an 89.0% reduction in genital warts related to vaccine types.
After a diagnosis of genital warts or vulvar or vaginal intraepithelial neoplasia, the quadrivalent vaccine was associated with a significant reduction in risk for any HPV
-related disease, regardless of HPV
The incidence of any HPV
-related disease was 20.1 and 30.1 per 100 person-years for vaccine and placebo recipients, respectively (risk reduction, 35.2%).
For disease related to HPV
vaccine types, the risk reduction was 64.4%.
The average time to first diagnosis of genital warts after vaccination was 1.4 years in the vaccine group and 2.1 years in the placebo group.
Vaccination was associated with 46.8% less recurrence of genital warts related to HPV
vaccine types, but this reduction was not statistically significant.
The authors conclude that the quadrivalent HPV
vaccine was associated with reduced incidence of any subsequent cervical, vaginal, or vulvar intraepithelial cancer in women previously diagnosed and treated for disease, and that this reduction was effective for both HPV
vaccine and nonvaccine types.
They also note that the vaccine did not reduce progression of infection of the preexisting HPV
infection in women who were already infected with HPV
at the time of vaccination.
The benefits of HPV
vaccine are not limited to young, sexually naive women and may be used as prophylaxis in older women with preexisting cervical, vaginal, or vulvar disease.
The quadrivalent HPV
vaccine is associated with reduced risk for subsequent HPV
-related disease for the vaccine and nonvaccine HPV
types in women who undergo cervical surgery.
Among women with genital warts or cervical, vulvar, or vaginal disease, the quadrivalent HPV
vaccine is associated with reduced future risk for vaccine and nonvaccine HPV