Reports

Insights Into Tight Rheumatoid Arthritis Control and Treating-to-Target Approaches
Success of Biologics in Rheumatoid Arthritis: From Efficacy of IL-6 Inhibition to Validation of Targeting New Inflammatory Pathways

Reducing the Burden of HPV Disease Through Successful Vaccine Uptake

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 - EUROGIN 2011 European Research Organization on Genital Infection and Neoplasia Congress

Lisbon, Portugal / May 8-11, 2011

Three years into the most successful adolescent vaccination program ever launched in Australia, a marked decline in genital warts (GWs) continues to be observed among vaccine-eligible Australian women, researchers reported during the scientific sessions. Herd immunity has also been reported among heterosexual (HS) men and even non-resident young women as well.

From July 2007 when the national quadrivalent human papillomavirus (HPV) vaccine program was launched, “We have seen a 73% decline in the proportion of young Australian women presenting with GWs to our sexual health clinics (SHCs) and there is no sign of that decline abating,” Prof. Basil Donovan, Program Head, National Centre in HIV Epidemiology and Clinical Research, Sydney, Australia, told EUROGIN delegates.

There has been a corresponding 35% decline in GWs among HS men, he added, a reflection of herd immunity. “We attribute this decline in GWs to the quadrivalent HPV vaccination program and we think we will continue to see a decline as the [largely vaccinated] school cohort moves through our SHCs,” Prof. Donovan confirmed. He added, “Hopefully, it heralds a drop in HPV-related cancer as well.”

Other Health Benefits Due to HPV Decline

A hint that HPV-related high-grade cervical dysplasias are declining as a result of widespread vaccine uptake is now evident in the state of Victoria. “Since the start of the vaccine program, there has been a decline in high-grade cervical abnormalities in our very youngest women (<18 years),” reported Dr. Julia Brotherton, Medical Director, National HPV Vaccination Program Register, Melbourne, Australia, “and there also appears to be a trend towards a decline among the 18- to 20-year-olds now, too.”

Since pre-vaccine years, there has been a 14% decline in high-grade-cervical abnormalities per quarter. As Dr. Brotherton noted, this trend is not confined only to Victoria. In Queensland, for example, researchers are reporting a 43% reduction in high-grade cervical abnormalities in females between the ages of 15 and 19. “It’s only ecological data but it does suggest something is happening,” she noted.

Corroborating Evidence from Trials

What some are calling “a cascade of health benefits” from HPV vaccination are directly quantifiable based on clinical trial data as well. In the HPV-naive cohort enrolled in the FUTURE trials, Dr. Daron Ferris, Professor of Obstetrics and Gynecology, Georgia Health Sciences University, Augusta, noted that there was a 20% reduction in colposcopy; a 22% reduction in cervical biopsies; a 42% reduction in cervical excisions; and a 43% reduction in procedures for external genital lesions (EGLs), including vulvar and vaginal neoplasias and condylomas in women between the ages of 15 and 26. Among women between the ages of 24 and 45 who were already exposed to HPV, effects on each of these end points were more modest but still encouraging. The quadrivalent vaccine is in fact approved for women up to age 45.

End-of-study results from the bivalent vaccine trial showed that over a median follow-up of 43.7 months, the vaccine was 99% effective against vaccine type-specific cervical intraepithelial neoplasia =grade 2 (CIN2+) in the total vaccinated population. The bivalent vaccine was also largely effective against CIN2+ irrespective of HPV type.

“It’s important to realize that these trials were conducted over a relatively brief interval so we would expect these rates to increase over time,” Dr. Ferris observed. Noteworthy as well, the quadrivalent HPV vaccine reduced the risk of recurrent or new cervical disease by 47% and CIN2+ by 65% in women who had previously been treated for cervical disease prior to receiving the vaccine.

“There are good reasons to immunize people who have already received definitive therapy because we know they are at risk for subsequent disease and there is a reduction in that risk with vaccination which is helpful to know,” affirmed Prof. Margaret Stanley, Director of Research, Department of Pathology, Cambridge University, UK. She also argued that while a public vaccination program in older women might not be feasible, “women of all ages remain at risk for acquiring HPV infection and older age is associated with an increased risk of progression. It therefore may be of benefit to vaccinate sexually active older women, but the decision to do so should be based on a discussion between a woman and her physician.”

Benefits for Both Genders

Benefits from quadrivalent vaccination are not confined to women, reported Anna Giuliano, PhD, Chair, Department of Cancer Epidemiology, Lee Moffitt Cancer Center & Research Institute, Tampa, Florida, here at EUROGIN. The quadrivalent vaccine was shown to be “highly efficacious” in reducing EGLs in HS men and anal intraepithelial neoplasia (AIN) in men having sex with men (MSM), and it also reduced the need for EGL biopsies by 54.2% compared to placebo controls in clinical trials involving men. There was also a 47.7% overall reduction in surgical and non-surgical procedures in vaccine recipients compared to controls. Reduction in each of these end points remained statistically significant in the intent-to-treat (or “all-comers” population) at 45.7% and 38.1%, respectively. “Unlike what we have for cervical cancer, we have no screening for cancer caused by HPV in men,” she stated, “so the availability of a highly efficacious vaccine that prevents HPV infection and related disease in men provides us with a unique opportunity to decrease disease risk in men and potentially their partners.”

Indeed, as Dr. Giuliano pointed out, HPV infection—primarily HPV 16—causes a lot of disease in men. “Men are 3 to 5 times more likely to get oropharyngeal cancer than women,” she confirmed. Men are also more likely to develop GWs. Although MSM are at significantly higher risk for anal cancer than HS men, anal cancer is increasing in HS men, almost all of which is caused by HPV 16 and 18. Similarly, the incidence of HPV-related head and neck cancer (primarily in the base of the tongue and tonsils) is increasing dramatically in the US and elsewhere. In 1974, for example, 18% of head and neck cancer in the US was related to HPV; in 2005, that proportion had risen to 32%, with rates now increasing at approximately 5% per year.

These alarming trends in the rising incidence of HPV-related disease in men provide the rationale for a gender-neutral HPV vaccination policy. Indeed, as Dr. Giuliano noted, the burden of HPV-related disease in men is equal to if not greater than that seen in women. “HPV is a potent carcinogen,” she told delegates here. “We know it causes multiple cancers in men and in women and that recipients of the quadrivalent vaccine are protected against all disease end points against which the vaccine has demonstrated efficacy; for many of these cancers, the vaccine is the only way we have an opportunity to prevent them. So we have to ask, ‘Is it ethical not to vaccinate men and allow them to personally benefit from a vaccine that works as well in men as it does in women?’ As a society, it’s a question we now should be asking.”

Long Term Safety and Protection

Safety data from The Female Safety Study, based on a large, retrospective cohort study involving 189,629 females, are also extremely reassuring. All subjects received at least 1 dose of the quadrivalent vaccine as part of routine practice care. An independent Safety Review Committee reviewed all study findings and determined that there was no association between vaccination and pre-specified health events, including congenital abnormalities, miscarriages, 16 specific autoimmune and neurologic conditions (including Guillain-Barré syndrome), venous thromboembolism and death within 6 months of patients receiving any dose of the quadrivalent vaccine. Syncope on the day of vaccination and possible local skin reactions within 14 days were reported in association with vaccination; otherwise, no other safety signals were detected for any health event resulting in an ER visit or hospitalization within 6 months of each dose.

Long-term HPV protection is also critical; in the case of the quadrivalent HPV vaccine, data from the 4 Nordic countries show no breakthrough HPV 16/18-related CIN 2+ at 7 years’ follow-up in their per-protocol FUTURE cohort.

In another study, Dr. Ferris reported that 93.3% of 9- to 15-year-old males and females who received the quadrivalent vaccine 6 years earlier maintained their antibody responses to HPV 6, 11, and 16 while 75% maintained antibody responses to HPV 18 (Seronegativity as measured by the 4-HPV type competitive Luminex Immunoassay does not mean loss of protection against HPV infection). Speakers here agreed that the HPV vaccines are highly immunogenic, producing significantly greater antibody titres against HPV vaccine types than are needed to protect against infection. “Vaccination of adolescents prior to their sexual debut provides durable protection,” Dr. Ferris said in a press briefing, “and the vaccine has a favourable long-term safety profile.”

Summary

The burden of disease related to HPV infection extends beyond young females and includes sexually active older women and men. The availability of HPV vaccines to reduce this disease burden makes it possible to proceed with important public health initiatives, yet it also depends on physician recommendations to their patients with current findings already indicating a cascade of health benefits in men and women that appear durable and safe over long-term follow-up. The future promise of widespread vaccine uptake is encouraging.

We Appreciate Your Feedback

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