October 28, 2010 — A massive multinational cervical cancer study described as “the benchmark for all time” has confirmed that 8 human papillomavirus (HPV) types cause more than 90% of all cervical cancers worldwide, and that HPV 16, 18, and 45 cause 94% of cervical adenocarcinomas.
The study was published online October 15 in the Lancet Oncology.
The research team, led by Silvia de Sanjose, MD, from Institut Català d’Oncologia-Catalan Institute of Oncology in Barcelona, Spain, concludes that “HPV types 16, 18, 31, 33, 34, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines.”
Maurie Markman, MD, vice president of patient oncology services and national director for medical oncology at Cancer Treatment Centers of America, in Philadelphia, Pennsylvania, told Medscape Medical News: ” I suspect the next generation of cervix cancer vaccines will specifically include each of the 8 HPV types noted in this paper, since this will cover 90% of the cases of cervix cancer.”
Currently, the 2 HPV vaccines on the market — Gardasil (Merck & Co) and Cervarix (GlaxoSmithKline) — protect against subtypes 16 and 18; together, these cause 70% of cervical cancer. In addition, Gardasil offers protection against 2 other subtypes (HPV 6 and 11) that cause genital warts.
However, there has been some evidence that the current vacciness might offer at least some cross-protection against other cervical cancer subtypes. A Merck research team, led by Janine Bryan, PhD, reported that Gardasil immunization induces antibodies capable of neutralizing HPV 45 in vitro (Hum Vaccin. 2007;3:109-115). The cross-reactive, cross-neutralizing antibodies were generated at reduced titers, compared with vaccine-specific types, and the researchers emphasized that antibody titers required for cross-protection against nonvaccine types were not known at that time.
The mechanism behind the cross-neutralization is that a single HPV species can contain several types. The HPV A9 species that contains type 18 also contains type 45. The HPV A7 species that contains type 16 also contains type 58, which was linked to cervical cancer in the de Sanjose multinational study.
There are also conclusions from the latest study on HPV screening. The researchers note that “our results also suggest that type-specific, high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45.”
HPV 16, 18, and 45 are the most common types, and occur at a much younger age than other high-risk HPV genotypes. As such, these 3 HPV types should be the focus of future type-specific HPV screening, say the authors.
Dr. de Sanjose reports receiving consultancy fees from Qiagen, Sanofi, and GlaxoSmithKline. Dr. Wheeler reports receiving research funding from Roche Molecular Systems, Merck & Co., and GlaxoSmithKline, and travel support from GlaxoSmithKline.