Reports

New Options Emerging for Cholesterol Lowering in Patients Not Adequately Controlled on Statins
Early Diagnosis and Treatment of Risk Factors for Osteoporosis Offer Major Opportunity Reduce Fracture Risk in China

Dramatic Reductions in Cervical Cancer Possible with New 9-valent HPV Vaccine

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 - 29th International Papillomavirus Conference (HPV 2014)

Seattle, Washington / August 21-25, 2014

Seattle -  Worldwide, the human papilloma virus (HPV) causes over 600,000 cases of cancer in men and women every year, cervical cancer by far and away being the most common. Prevention of approximately 70% of all cervical cancer is now possible with vaccination against HPV types 16 and 18. However, at least 20% of cervical cancer is caused by 5 other HPV types including 31, 33, 45, 52, and 58. A new 9-valent HPV vaccine has been tested in young women and found to be non-inferior to the quadrivalent vaccine against the 4 HPV types contained in both vaccines. In addition, the 9-valent HPV vaccine is highly protective against HPV-related disease caused by the additional 5 HPV types. Debate continues about the potential efficacy of using a 2-dose rather than the currently recommended 3-dose schedule but in the meantime, the impact of widespread uptake of the quadrivalent vaccine has already been well documented in Australia and elsewhere. The best policy to prevent HPV-related disease in men is to offer a gender-neutral vaccine policy, speakers here agreed, and some provinces are beginning to do so in recognition of the need to protect males from HPV-related disease as well as females.

Chief Medical Editor: Dr. Léna Coïc, Montréal, Quebec

“There is an enormously large reservoir of HPV in the world,” Dr.  Xavier Bosch, Chief of the Cancer Epidemiology and Registration Unit, Catalan Institute of Oncology, Barcelona, Spain reminded delegates here. Out of all of the diseases HPV causes, “cervical cancer is the most important of them,” he added. The key types of HPV that are driving cervical cancer differ slightly world-wide but approximately 70% of cervical cancer is caused by high-risk oncogenic types 16 and 18, with approximately 20% caused by HPV types 31, 33, 45, 52 and 58.

“These 5 additional HPV types are estimated to contribute to 100,000 cases of cervical cancer each year,” Dr. Bosch observed. Looking at the potential impact that the new 9-valent HPV vaccine could have, Dr. Bosch first noted that the 9 HPV types contained in the vaccine contribute to about 90% of cervical cancer world-wide—suggesting that the 9-valent vaccine would confer about 20% more protection against cervical cancer than vaccines against HPV types 16 and 18 alone. 

The degree to which the same 5 HPV types contribute to other kinds of cancer ranges from about 15% for cancer of the vulva and vagina to about 5% for anal cancer. Dr. Bosch also calculated that the 9-valent vaccine would confer an additional 30% protection against cervical intraepithelial neoplasia (CIN) 2 and 3, and about 20% more protection against CIN1.  Thus, the predicted impact of the 9-valent vaccine containing HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58 if given to a vaccine-naïve cohort in a gender-neutral program would reduce the lifetime risk of cervical cancer by 90%; all HPV-related cancers in men and women by 77%; high-grade cervical dysplasia by 80%, and genital warts (GWs) in men and women by 90%.

“And the 9-valent vaccine should work equally well in any region of the world despite variability of HPV types in some countries,” Dr. Bosch affirmed.

V503 Vaccine Trial Results

In the pivotal phase III trial, over 14,000 young women between 16 and 26 years of age were randomized either to the quadrivalent vaccine or to the new 9-valent HPV vaccine (V503). Subjects were followed for one year. As noted by Dr. Elmar Joura, Associate Professor of Obstetrics and Gynecology, Medical University of Vienna, Austria, the study was conducted as a non-inferiority trial to demonstrate potential equivalency between the quadrivalent vaccine and the 9-valent formulation. At month 7, following receipt of 3 doses of each vaccine, virtually identical geometric mean antibody titers against HPV 6, 11, 16 and 18 were seen between the two vaccines.

The 9-valent vaccine also reduced the combined incidence of high-grade cervical, vulvar and vaginal disease caused by HPV types 31, 33, 45, 52 and 58 by 97%. The same level of protection was also observed against the combined incidence of cervical, vulvar, and vaginal disease of any grade caused by the same 5 HPV types, while the vaccine was 96% effective against persistent HPV infection at 6 months.

“Results were very consistent,” Dr. Joura said. Furthermore, there was a 97% reduction in the need for biopsies of lesions caused by the 5 HPV types and an 87.5% reduction in definitive therapy. The vaccine has a good safety profile as the women in the study tolerated the vaccine very well.”

Two Versus Three Doses

Alternative dose schedules were also discussed by several speakers including giving 9 to 14-year-olds only 2 doses of the HPV vaccine 6 months apart instead of the currently recommended 3-dose schedule. This is in part to address cost issues and poor uptake rates of the HPV vaccine in countries such as the US where only about one-third of girls and one-fifth of boys have received all 3 doses of the HPV vaccine. Immunogenicity data suggest that the 2-dose schedule may be non-inferior to the 3-dose schedule, at least in young girls.

As reported by Dobson et al. (JAMA 2012:309:1793-802), among girls who received 2 doses of HPV vaccine 6 months apart, responses to HPV-16 and HPV-18 one month after the last dose were noninferior to those of young women who received 3 doses of the vaccine within 6 months. However, as the authors point out, because of the loss of noninferiority to some genotypes at 24 to 36 months with the 2-dose regimen, more data on the duration of protection are needed before reduced-dose schedules can be recommended. There is also no clinical efficacy data supporting the 2-dose regimen at this point in time.

The World Health Organization recently recommended the 2-dose schedule given 6 months apart for girls under the age of 15.

Rapid and Dramatic Changes

The fact that the quadrivalent vaccine has been associated with rapid and dramatic changes in the prevalence of HPV-associated lesions is best illustrated by the Australian experience. As reported by Dr. Julie Brotherton, from the National HPV Vaccination Program Register, Australia, 6 years after the initiation of the HPV program in Australia, “we have detected a substantial fall in vaccine-targeted HPV genotypes in vaccinated women; a lower prevalence of vaccine-targeted types in unvaccinated women—suggesting herd immunity—and a possible indication of cross-protection”.

Australian colleagues under Smith et al. also reported that there has been a “marked decline” in hospital admissions involving a diagnosis of GWs in young people following the launch of the HPV vaccination program in 2007. Here in Canada, Dr. Marc Steben, Public Health Institute of Quebec, Montreal, and colleagues reported that there has been a significant 45% decline in the incidence of GWs in women under the age of 20 as well as a significant 19% decline among women 20 to 24 years of age (P<0.0001) since the quadrivalent vaccine was introduced as part of a public program in September 2008.

A smaller but still significant 21% decline in GWs has also been seen among males under the age of 20 across the same time interval. As was reported by Manitoba-based researchers, the incidence of GWs in men is rising in the province, especially in urban areas, and suggests that HPV immunization programs that include boys may be required to reduce the burden of HPV-related disease in males.

Indeed, HPV-related cancers in men are common both in the US and globally, as discussed by Dr. Joel Palefsky, Professor of Medicine, University of California at San Francisco. Unlike cervical cancer screening, however, there is no screening program to pick up early HPV infection in males. “So that leaves us with primary prevention,”
Dr. Palefsky said. The quadrivalent vaccine has already been shown to protect men against anogenital infection and cancerous precursor anal lesions.

“The good news is that this vaccine would be expected to have a very substantial impact on these cancers in men because such a high proportion of them are associated with HPV 16,” Dr. Palefsky observed. “So I think the best approach to reducing the burden of male cancer is to be very aggressive about implementing vaccination in boys.”

Currently in Canada, only Prince Edward Island offers a school-based HPV vaccination program for boys. However, Alberta is about to launch a similar program as public acceptance of male vaccination against HPV gains momentum. 

 

 

We Appreciate Your Feedback

Please take 30 seconds to help us better understand your educational needs.