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.

EUROGIN 2006 6th International Multidisciplinary Congress

Paris, France / April 23-26, 2006

As reported by Dr. Nubia Muñoz, former Director, Cancer Epidemiology, International Agency for Research on Cancer, Lyons, France, the human papillomavirus (HPV) genotypes 16 and 18 are responsible for about 70% of cervical cancer and high-grade lesions of the cervix and for approximately 30% of other genital cancers, especially of the vulva, vagina and anus. Types 6 and 11 are responsible for about 90% of condyloma acumination in both men and women and for 5% to 25% of low-grade cervical lesions and recurrent respiratory papillomatosis.

More than 1500 new cases of cervical neoplasia are diagnosed each year in Canada. Invasive cervical cancer is the second most common cancer in women between the ages of 20 and 44 worldwide. Sexually-transmitted HPV infection is responsible for 400 cancer deaths annually among Canadian women, making it twelfth among causes of cancer death nationally in that population.

Reporting on combined three-year results of recent phase III trials of the quadrivalent vaccine (i.e. covering HPV genotypes 6, 11, 16 and 18) involving nearly 20,000 women, Dr. Muñoz noted that per-protocol analysis (which included only women who met entry criteria, received all three doses of vaccine and had no major procedural violations) demonstrated 100% efficacy for CIN-1/2/3 and CIN-3 (also known as adenocarcinoma in situ [AIS]). In addition, a modified intent-to-treat (MITT) analysis more closely resembling patients in real-world clinical practice was presented. It included women who received at least one dose of vaccine but may not have completed the full regimen and which did not exclude protocol violators. These findings confirmed that the quadrivalent vaccine is 100% effective in protecting against CIN-3/AIS and 99% effective against CIN-2/3 in a less strictly constructed population of patients.

“The quadrivalent vaccine is highly effective in preventing cervical cancer, cervical, vulvar and vaginal cancer precursors and genital warts caused by HPV 6, 11, 16 and 18. It is expected to have a truly remarkable impact on the lifetime risk of developing neoplastic and related HPV diseases,” Dr. Muñoz told delegates.

Regarding the bivalent vaccine, Dr. Diane Harper, Dartmouth Medical School, New Hampshire, reported that evaluation of a long-term follow-up study of vaccine efficacy, immunogenicity and safety at a mean of 42 months demonstrated 100% efficacy against CIN lesions associated with HPV genotypes 16 and 18. The high level of persistence was maintained with no interference between HPV types, she added.

Previous HPV Exposure

Some clinicians have been uncertain about whether women PCR-positive or seropositive for one or more of the HPV types would be safely protected from developing genital neoplasias caused by the remaining types if given the quadrivalent vaccine. If so, they reasoned, there would be no need to prescreen individuals for HPV infection before vaccination.

Dr. Daron Ferris, Director, Gynecologic Cancer Prevention Center, Medical College of Georgia, Augusta, analyzed subgroups from quadrivalent vaccine efficacy studies which did not include a screening phase and did not exclude protocol violators, resulting in some patients being positive to one or more HPV types at baseline. He noted that such individuals are more in line with real-world populations seen in clinical practice. Their most common prior infections were with HPV type 16 and least common with type 11.

Dr. Ferris reported, “The quadrivalent vaccine was 87.5% effective in preventing HPV 6/11/16/18-related CIN in women previously exposed to at least one of those types. It was 100% effective against CIN2/3 [cervical cancer precursors] and 91% effective in preventing HPV 6/11/16/ 18-related vulvar and vaginal neoplasias and genital warts, and prior exposure to those HPV types did not affect the vaccine’s efficacy against vaccine HPV types to which the person was naïve.” He added that there was no appreciable increase in injection-site reactions among women with serologic evidence of antibodies to an HPV type included in the vaccine. “We do not need to prescreen,” he recommended. “These data support universal vaccination for preventing lower genital tract neoplasia in women.”

Long-term HPV Protection

Because the risk of HPV infection is lifelong, Dr. Luisa Villa, Ludwig Institute for Cancer Research, São Paulo, Brazil, reported data on long-term protection from the longest efficacy evaluation of an HPV vaccine to date. She evaluated possible persistent HPV infection in a subset of 241 Brazilian and European patients who underwent more than five years of follow-up in the phase III trials described by Dr. Muñoz.

Dr. Villa reported that at up to 5.3 years’ follow-up, the combined incidence of HPV 6, 11, 16, 18 persistent infection or disease in vaccine recipients amounted to two cases compared to 45 cases in the placebo cohort, for an efficacy rate of 96%. However, both reported cases, an asymptomatic HPV 18 infection and a report of HPV 16 DNA, had earlier been observed within the first three years following vaccination in this subpopulation.

“Throughout the two-year extension period which followed the initial three-year follow-up, no cases of HPV 6, 11, 16, 18 persistent infection or cervical, vulvar, vaginal or external genital warts were observed in the vaccinated subjects, giving 100% of continuing efficacy,” Dr. Villa observed. “This is telling us that no additional cases that had not been observed during the three years of regular follow-up occurred in the two-year extension, which I think is very good news.” She added that two cases of HPV 16 infection that had been reported proved to be non-persistent.

Dr. Villa reported that the prophylactic quadrivalent HPV vaccine is highly effective through five years for prevention of persistent infection and disease caused by HPV 6, 11, 16 or 18. She added that there was no waning of immunity, i.e. no breakthrough cases of confirmed persistent infection or disease in the extended follow-up phase.

Genital Warts

According to Dr. Alex Ferenczy, McGill University, Montreal, Quebec, “The cost and psychological impact of genital warts on patients can be devastating and may be more distressing to them than having an abnormal Pap test. Genital warts are ugly, cosmetically unacceptable and may bleed, burn and itch. Consequently, HPV types 6 and 11, which account for roughly 90% of genital warts, have been included in the quadrivalent vaccine.” They pose a demoralizing clinical problem to the patient because virtually all of them require long, painful multiple therapies, with recurrences running up to 50%.

Although genital warts are benign, their clinical appearance and management can be severe and costly, both psychologically and medically. The reported lifetime prevalence of genital warts ranges from less than 2% to more than 10%. Dr. Ferenczy stated, “If it is true that 90% of warts can be prevented by vaccination, we will not see so many of them down the road when the youngsters become sexually active.”

Dr. Ferenczy observed that HPV has, until now, been an orphan in the clinical world. First, herpes overshadowed other viruses as the most distressing viral infection, then came HIV. He observed that people are now finally paying attention to HPV and that it is really interesting to see an agent that can prevent malignant genital disease get the attention it deserves. “In my opinion, the development of HPV vaccination is really the most relevant and important happening since the introduction of the Pap test 55 years ago,” he concluded.