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.

47th Interscience Conference on Antimicrobial Agents and Chemotherapy

Chicago, Illinois / September 17-20, 2007

The lifetime risk of sexually active men and women being infected with human papillomavirus (HPV) is at least 50% and in some settings, that risk is as high as 70%. Screening has dramatically reduced the incidence of cervical cancer, but it has led to a new development. “We have created a new disease—cervical intraepithelial neoplasia [CIN]—which we need to investigate and treat,” as Dr. Sven-Eric Olsson, Associate Professor of Obstetrics and Gynecology, Karolinska Institute at Danderyds Hospital, Stockholm, Sweden, told delegates here. With an estimated 40 million cases of high- and low-grade CINs worldwide, protection against HPV-related CIN could have a dramatic effect on health care delivery and cost.

Disease Incidence

In landmark trials, female participants between the ages of 16 and 26 were randomized to receive the quadrivalent vaccine or placebo. As part of these studies, subjects underwent Pap testing on day 1 and every six to 12 months thereafter for up to 48 months. In an analysis of the per-protocol population only (seronegative at day 1 and at month 7, three doses of the vaccine), Dr. Olsson and colleagues identified only six cases of CIN of any grade in vaccine recipients vs. 148 in placebo controls. For CIN grades 2 and higher, only one vaccine recipient developed high-grade dysplasia vs. 76 in placebo patients. As Dr. Olsson noted, this single case occurred in a woman who tested positive for both HPV type 16 and 52 but when her cervix was sampled following treatment, the sample tested positive for only HPV type 52.

“Through three years of follow-up, the quadrivalent vaccine was 96% effective in preventing HPV 6, 11, 16 and 18-related CIN including high-grade precancerous lesions of CIN 3 and AIS, and its efficacy was significant for all of the individual HPV types,” Dr. Olsson reported.

Pap Test Results

In a separate presentation, Dr. Olsson and colleagues tracked the impact of the same vaccination program on the incidence of abnormal Pap tests. All Pap tests and biopsies were processed at a central laboratory or at one of five regional laboratories. In a generally HPV-naïve population—the primary target for HPV vaccination, as Dr. Olsson noted—30% of placebo patients experienced at least one abnormal Pap test (any HPV type) over three years of follow-up. Most of these abnormalities required colposcopy follow-up, he added. Among vaccine recipients, there was a 48.3% reduction in the incidence of high-grade squamous intraepithelial lesions (HSIL); a 35.7% reduction in atypical squamous cells; a 32.9% reduction in atypical glandular cells; and a 26.2% reduction in atypical squamous cells of undetermined significance. Other types of abnormalities on Pap testing were also reduced but not to the same extent.

“Given these results, the impact of HPV 6/11/16/18-related Pap abnormalities is expected to be dramatic,” Dr. Olsson and colleagues concluded, “and the reduced burden of cytologic abnormalities associated with the quadrivalent HPV vaccine is likely to have a substantial impact on cervical screening programs and result in psychosocial and socioeconomic benefits.”

Cross-protection Against Other HPV Types

The first demonstration of cross-protection against other HPV types not contained in the vaccine was also presented here by Dr. Darron Brown, Professor of Medicine, Microbiology and Immunology, Indiana University School of Medicine, Indianapolis. As he noted, HPV types 16 and 18 are the two most common types in cervical cancer but they are followed by HPV types 45, 31, 33, 52 and 58.

In an analysis of the same phase III efficacy studies of the quadrivalent vaccine, FUTURE study group investigators found the vaccine prevented 45% of CIN grades 1 to 3 or AIS caused by HPV types 31 or 45, and 33% of CIN grades 1 to 3 or AIS caused by HPV types 31, 33, 45, 52, or 58.

Indeed, vaccination led to a 38% reduction in CIN 2 and 3 or AIS caused by 10 non-vaccine HPV types. These 10 types cause more than 20% of cervical cancer cases worldwide, investigators pointed out. They also noted that reductions in HPV-related disease were most apparent for the A9 species, which causes most cases of CIN 2 or 3 and AIS.

“We believe that antibodies against the vaccine types have the ability to bind and neutralize closely related types, therefore giving protection against both infection and, more importantly, against disease,” Dr. Brown explained. “I think we can expect even greater returns from this vaccine than protection against only HPV types in the vaccine, because the high degree of cross-protection against additional oncogenic HPV types may provide an extra measure of protection for young women vaccinated with the quadrivalent HPV vaccine.”

Other Cancers and HPV

Studies have not been carried out to evaluate the protective efficacy of vaccination against other cancers but there is good reason to believe that widespread vaccination could have a substantial impact on head and neck cancer as well as cancer of the anus and penis.

As noted by Dr. Joel Palefsky, Professor of Medicine, University of California, San Francisco, HPV infection in men is an important public health concern, primarily because men can transmit HPV to their female partners, with all of its potential sequelae and secondly, approximately 60% of men who have sex with men and over 90% of all HIV-positive men are infected with HPV. “Like cervical cancer, most anal cancers are associated with HPV infection,” Dr. Palefsky observed. The amount of penile cancer caused by HPV ranges from under 10% according to some studies to over 50% in others.

The most important HPV type in head and neck cancer is HPV 16. While most cases of head and neck cancer are due to tobacco and alcohol use, “a distinct subset is attributable to oropharyngeal HPV,” noted Dr. Maura Gillison, Assistant Professor of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, “and HPV-related head and neck cancers have increased over 5% per year in both the US and in Sweden.”

Although rare, recurrent respiratory papillomatosis (RRP) is a potentially fatal disease resulting from vertical transmission of HPV from mother to child during delivery. “Surgery is not curative,” noted Dr. Craig Derkay, Professor of Otolaryngology and Pediatrics, Eastern Virginia Medical School, Norfolk, “and multiple operations are required to remove the growths which are associated with substantial morbidity and medical costs.” Prevention of HPV transmission to the infant by preventing infection in the mother would dramatically reduce the incidence of RRP, he suggested.

“From the standpoint of the otolaryngology community, we stand behind recommendations to use the HPV vaccine because of its potential to prevent RRP and head and neck cancers,” Dr. Derkay told delegates, adding that if safety and efficacy data for the bivalent and the quadrivalent vaccine are equivalent, “we would still favour the use of a quadrivalent vaccine that covers 6, 11, 16 and 18 over a bivalent one that only covers 16 and 18.”