Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

PRIORITY PRESS - 26th International Papillomavirus Conference

Montreal, Quebec / July 3-8, 2010

According to Dr. Suzanne Garland, Director, Microbiological Research, Royal Women’s Hospital, Melbourne, Australia, genital warts (GWs) are the most common condition seen in sexual health services in the country. Multiple visits are often required to achieve reductions or clearance and they are also associated with a significant psychosocial burden.

In one study cited by Dr. Garland, levels of psychological stress were as high among women with GWs as those reported by women with high-grade cervical intraepithelial neoplasia (CIN). In Canada’s own PISCES (Psychological Impact of Cervical Screening and Condylomas: An Epidemiology Study), researchers found that 67% of women with a first episode of GWs experienced anxiety or depression compared with 32% of controls. Several health domains were also adversely affected in both men and women with a first or recurrent episode of GWs and their negative impact on health-related quality of life measures persisted as long as the lesions were present.

Successful Australian HPV Vaccination Campaign

An update of the previously reported Australian experience on the incidence of GWs following widespread uptake of the quadrivalent vaccine confirmed that vaccination of approximately 80% of young females has led to a rapid decline in GWs in that country. Between mid-2007 when the Australian national HPV vaccination campaign was introduced until the end of 2009, “There has been about a 60% decline in the incidence of GWs in females 27 years of age and younger, and about a 30% reduction in GWs in heterosexual men of the same age,” reported Dr. Andrew Grulich, University of New South Wales, Sydney, Australia. He added that this was “clear evidence of herd immunity,” as there has been no corresponding reduction in the incidence of GWs in older heterosexual men or in men who have sex with men (MSM).

The incidence of GWs peaks in women between the ages of 20 and 24, Dr. Daron Ferris, Medical College of Georgia, Augusta, told delegates. Adult women are not immune from HPV infection, however, and new infections from HPV 6 and 11—the primary cause of almost all GWs—persist in older women as well. On examination of end-of-study efficacy against the four HPV vaccine types in women between the ages of 24 and 45, Dr. Ferris and colleagues showed that the quadrivalent vaccine was 88.7% effective against persistent HPV infection, CIN or external genital lesions (EGL) and 100% effective against condyloma at a mean follow-up of 3.8 years (per-protocol analysis). “The study was not powered for the full analysis set,” Dr. Ferris cautioned. Nevertheless, what was essentially an intent-to-treat (ITT) analysis demonstrated that the quadrivalent vaccine was still 47.2% effective against persistent infection, CIN or EGL and 41.8% effective against condyloma.

It is widely acknowledged that HPV vaccination should be targeted to sexually-naive young girls between the ages of 11 and 13 years. “However, women who are older and who have missed the opportunity to get vaccinated at a young age often still want protection,” Dr. Elmar Joura, Medical University of Vienna, Austria, told delegates. Results from the pivotal FUTURE I and II studies showed that among women between the ages of 16 and 26 years who were seropositive for HPV at baseline, the quadrivalent vaccine was still 100% effective against CIN, GW and vulvar intraepithelial neoplasia (VIN) despite prior infection. “The vaccine generates a remarkably anamnestic response in women who are seropositive pre-vaccination and prevents re-infection or reactivation of HPV,” Dr. Joura observed, “Thus, women do benefit from vaccination after they have cleared a previous infection.” Similarly, the vaccine reduced persistent infection or any clinical end point related to HPV 6, 11, 16 and 18 by approximately 90%, CIN of any grade by 95% and EGL by 100% relative to placebo in women between the ages of 24 and 34 and in those between the ages of 35 to 45, Dr. Joura noted.

“We then looked at whether or not there was a reduction in HPV-related recurrent or new disease after treatment for cervical disease,” he continued. Irrespective of HPV type, results from this analysis showed that following treatment for cervical disease, the quadrivalent vaccine reduced any HPV-related disease by 46%, any cervical disease (CIN1+) by 48%, any CIN2+ disease by 65%, any GW/VIN or vaginal intraepithelial neoplasia (VaIN) by 47% and any HPV 6-, 11-, 16- or 18-related disease by 79%. The same analysis showed that after being diagnosed with GWs, VIN or VaIN at baseline, the quadrivalent vaccine reduced any HPV-related disease by 35%, any CIN1+ by 46%, any CIN2+ by 41%, any GW/VIN or VaIN by 23% and any HPV 6-, 11-, 16- or 18-related disease by 64%.

Dr. Joura concluded, “Vaccination of a woman with past or existing HPV-related disease is warranted and should be considered at an individual level.”

Male Vaccination

The Australian experience showing a decline of approximately 60% in the incidence of GWs following widespread uptake of the quadrivalent vaccine appears to have plateaued in 2010, suggesting that the only means by which to further reduce the burden of HPV-related disease is to vaccinate males. Certainly there has been a shift in favour of a “gender neutral” vaccination policy given with the high burden of HPV-related disease now being recognized in males.

As discussed by Dr. Anna Giuliano, Chair, Department of Epidemiology and Genetics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, the annual number of new cases of HPV-related cancers in US men totalled over 11,000 based on 2009 estimates. The percentage of HPV-related cancers affecting men ranges from about 25% for cancers of the oral cavity, oropharynx and larynx to 90% for anal cancer. In fact, in MSM, the incidence of anal cancer is 30-fold higher than in the heterosexual population and in MSM co-infected with HIV, the incidence of anal cancer is 80-fold higher, underscoring the importance of HPV prevention in men. “There is no association with age and HPV prevalence either,” stated Dr. Giuliano, “and this means that men remain at risk throughout their lifetime for HPV infection.” Unlike screening for cervical cancer in women, there is no routine screening available to detect and treat precancerous lesions in men, as she also noted, another argument in favour of vaccination in men. In the phase III trial testing the efficacy of the quadrivalent vaccine against HPV 6-, 11-, 16- and 18-related EGL in men, there were only three cases of EGLs in the vaccine group compared with 31 in the placebo group, for a vaccine efficacy of 90.4%.

At this year’s meeting, Dr. Joel Palefsky, Professor of Medicine, University of California, San Francisco, presented findings on the efficacy of the quadrivalent vaccine for the prevention of anal intraepithelial neoplasia (AIN) in MSM from the same study. For this substudy, 602 MSM between the ages of 16 and 26 years were randomized to the quadrivalent vaccine or placebo.

At a median follow-up of 2.5 years, the quadrivalent vaccine reduced HPV 6-, 11-, 16- and 18-related AIN and anal cancer by 77.5%, condyloma by 100% and AIN 2 or worse by 74.9% (per-protocol analysis). In the full analysis set (ITT), the vaccine still reduced any vaccine type HPV-related AIN or anal cancer by 50.3%, condyloma by 57.2% and any high-grade AIN (2 or worse) by 54.2%. As in the female studies, there were no serious safety signals in men receiving the vaccine, Dr. Palefsky reported. “The short follow-up time in this study spoke volumes about the high incidence of the HPV disease in MSM and the high efficacy of the vaccine. It is my belief that the HPV vaccine is a potentially important tool for the prevention of anal cancer in this at-risk population.”

Bivalent Vaccine

The bivalent HPV vaccine is also highly effective against HPV 16- and 18-related disease, as reflected in the results from the pivotal PATRICIA (Papilloma Trial Cervical Cancer in Young Adults) study. At a mean follow-up of 34.9 months, vaccine efficacy against CIN2+ associated with HPV 16 and 18 was 92.9% in the primary analysis and 98.1% in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types. Vaccine efficacy against CIN2+, regardless of HPV type, was 30.4% in the total vaccinated cohort (TVC) (all women, regardless of baseline HPV status) and 70.2% in the total non-vaccinated cohort.

Summary

Looking beyond cervical cancer and diseases that can be prevented in both males and females supports clinical decisions to vaccinate both genders. In addition, it was put forward by health care modellers that while it may not be cost-effective to vaccinate boys in a public program where there is a high coverage rate of females, gender-neutral vaccination may prove cost-effective when all potentially preventable HPV disease is included and cytology intervals prolonged in women.