Update on the 9-valent HPV Vaccine: Taking Prevention to a New Level
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 - 13th Annual Primary Care Today
Toronto, Ontario / May 6-9, 2015
Toronto - A new 9-valent vaccine against the human papilloma virus (HPV) has recently been approved by Health Canada and is indicated for use in young girls and women between 9 and 45 years of age as well as in boys and men between 9 and 26 years of age. Containing an additional 5 highly oncogenic HPV types over the quadrivalent vaccine, the 9-valent HPV vaccine promises to take prevention to a new level by offering protection against disease caused by these additional oncogenic types including cervical and anal cancer, precancerous or dysplastic lesions and genital warts. The additional protection against HPV-related disease is highly clinically relevant and primary care providers need to offer the vaccine to appropriate vaccine candidates and discuss its potential with individual patients of both genders. Lessons from an expert in immunization follow.
Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec
Just when primary care providers thought they knew everything there was to know about preventing human papilloma virus (HPV)-related disease, a new HPV vaccine has just been approved by Health Canada that now needs to be integrated into clinical practice.
The new “enhanced” HPV vaccine contains 5 additional high-risk oncogenic HPV types in addition to the four types already contained in the quadrivalent HPV vaccine. So while both vaccines contain HPV types 6 and 11 to prevent genital warts (GWs) as well as the two major high-risk oncogenic types 16 and 18, the 9-valent HPV vaccine (GARDASIL® 9) also contains HPV types 31, 33, 45, 52 and 58 and offers protection against cervical, vulvar, vaginal and anal cancers along with precancerous lesions caused by these additional five HPV types. So how much extra protection can physicians expect from the 9-valent or “nonavalent” vaccine compared to the quadrivalent vaccine?
“Overall, the new vaccine should cover another 10 to 20% of cancers because that is the amount of cancer those more rare subtypes cause,” Dr. Vivien Brown, Assistant Professor of Family & Community Medicine, University of Toronto, said in an interview. Dr. Brown was speaking about HPV prevention at a pre-conference symposium held in advance of “pri-med”, formerly known as Primary Care Today. That 10 to 20% additional protection translates into impressive numbers when compared to protection afforded by the quadrivalent vaccine.
For example, the enhanced vaccine should prevent between 90 and 95% of all cervical cancers compared with 70 to 75% provided by the quadrivalent vaccine. It is also expected to prevent between 75 to 80% of all cervical intraepithelial neoplasias (CIN) 2/3 and 50 to 60% of all CIN1 lesions compared with about 50% and 30 to 35%, respectively, for the quadrivalent vaccine. The five additional high-risk oncogenic types are also expected to prevent over 70% of vaginal cancers; over 75% of vaginal (VaIN) 3 lesions; 65% of vulvar cancers, and over 91% of vulvar (VIN) 3 lesions.
“This vaccine is highly efficacious,” Dr. Brown observed. “The numbers are robust and there is an excellent [immunological] response.” This is at least as true for males as it is for females, she added. Furthermore, protection against HPV infection appears to persist for a long time. Follow-up of the cohort of young girls who were originally vaccinated with the quadrivalent vaccine now extends to 10 years and there is no sign of waning protection yet, Dr. Brown said. There is also no question from any of the regulatory organizations which monitor the safety of vaccines that there are any safety concerns regarding either the quadrivalent or the nonavalent vaccine.
“Whether it’s the World Health Organization, the Food and Drug Administration in the US or any of the European agencies, everybody who’s looked at the risk of adverse events (AEs) from the quadrivalent vaccine has found no significant signal for any long-term risk and more than 40,000 million doses of the vaccine have been given world-wide,” Dr. Brown said.
Reduce HPV-related Disease
“We can also say with confidence that the vaccine reduces the risk of HPV-related disease,” Dr. Brown added. This is best demonstrated by the dramatic reduction in GWs now being reported in Australia. In 2007, Australia launched
their national HPV immunization program with over 85% uptake in young females. Five years into the national program, the Australians are reporting over a 72% decline in GWs in females between 21 and 30 years of age and over a 92% decline in GWs in females under the age of 21 compared with the pre-vaccination period.
Over the same 5-year follow-up, the incidence of GWs has also declined in heterosexual men whereas there has been no effect on the incidence of GWs in men who have sex with men (MSM) or bisexual men.
“We don’t spend money treating disease if we start preventing that disease and the Australians have shown us the way,” Dr. Brown said.
How to Use the 9-Valent Vaccine
How physicians should use the 9-valent HPV vaccine is still uncertain. Currently, the National Advisory Committee on Immunization (NACI) has not issued any recommendations regarding its use in either gender and physicians need to follow NACI recommendations when they are released. In the meantime, Dr. Brown herself suggests that if a patient is still naive to the quadrivalent vaccine, then physicians should favor the 9-valent vaccine as it offers significantly greater protection against the burden of HPV-related disease.
If a patient has already received one or two doses of the quadrivalent vaccine, Dr.Brown herself favors finishing off the 3-dose schedule with the 9-valent vaccine. Recommendations regarding the use of the 9-valent vaccine in patients who have not yet finished their 3-dose series with the quadrivalent vaccine have not yet been released. The group on which there is no data includes patients who have received all 3 doses of the quadrivalent vaccine. NACI is likely to address this issue when new guidelines emerge. From her own perspective, Dr. Brown felt there was “good enough benefit” from the 9-valent vaccine to offer it to patients even if they have finished the 3-dose quadrivalent vaccine series.
“There’s also no risk in receiving the nonavalent vaccine on top of the quadrivalent vaccine,” she added. The product monograph supports the safety of giving 3 doses of the 9 valent vaccine after a patient has received 3 doses of the quadrivalent vaccine. If a patient has already been exposed to an HPV type, neither vaccine is going to offer protection against that individual HPV type—but it will help protect recipients from infection with other HPV types. Furthermore, even women who have developed clinically significant HPV-related disease benefit from HPV vaccination following treatment of the disease.
This has been demonstrated in a number of cohorts, but in one cohort of women who were vaccinated after loop electrosurgical excision procedure for CIN2-3 disease (Gynecol Oncol. 2013;130:264-8), the risk of recurrence was almost 3 times higher at 7.2% for patients who did not receive the quadrivalent vaccine compared to 2.5% for those who did (P<0.01). The risk of new HPV disease in another cohort of patients previously treated for cervical disease also showed a 79% decrease of HPV 6, 11, 16 or 18-related disease following receipt of the quadrivalent vaccine (Joura et al. Annual International Papillomavirus Conference and Clinical Workshops. 2010).
“It’s also never too late to get the vaccine,” Dr. Brown noted. In Canada, HPV infection rates are highest in individuals under the age of 20 but they start to rise again after the age of 60. In the absence of Canadian recommendations, primary care providers need to discuss the advantages of the new vaccine with individual patients and let patients decide what course of action is best for them.
Lastly, there is the question of paying for the vaccine outside of a school-based program. “If the vaccine was important enough to get, surely the government would have funded it?” patients might ask. To this, Dr. Brown simply replies: “When you have a baby, you’re not allowed to leave the hospital without a car seat but nobody hands you a car seat, you have to buy it and there’s lots of recommendations we made that are unfunded,” she said. “If we eradicate HPV, we are going to prevent cancers and I think being able to prevent not just HPV infection but cancer is tremendously exciting and it’s tremendously responsible of young women and men to be immunized to protect themselves as well as their partner and that’s what this is all about.”