Eight human papillomavirus (HPV) types (16, 18, 45, 33, 31, 52, 58, and 35) are responsible for over 90% of all cervical cancer cases worldwide, and should be the target of the next generation vaccines, according to the largest study of HPV genotypes to date, published Online First in The Lancet Oncology. 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 three HPV types should be the focus of future type-specific HPV screening.

Cervical cancer is the second most common cancer among women worldwide, and is predicted to result in nearly 328 000 deaths in 2010. The disease is caused by high-risk types of HPV. More than 118 different types of HPV have been identified, about 40 of these infect the genital tract, and 12 are known to be cancer causing. To effectively vaccinate against major cancer causing HPV types reliable information on the worldwide contribution of specific types of HPV to invasive cervical cancers is needed, particularly in developing countries where 80% of cases occur.

In this study, an international team led by Silvia de Sanjosé from the Catalan Institute of Oncology in Barcelona, Spain, investigated the role of different HPV types to the global incidence of invasive cervical cancer.

Samples from 10 575 cases of invasive cervical cancer diagnosed between 1949 and 2009 were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. PCR and DNA testing were used to identify the HPV genotype present in these tissue samples.

Over the 60 year study period, the eight most common HPV types identified were (in descending order of frequency) 16, 18, 45, 33, 31, 52, 58, and 35. Together they accounted for 91% of all cases of cervical cancer.

HPV 16, 18, and 45 were found in 75% of the most common type of cervical cancer (squamous cell) and 94% of adenocarcinomas (the second most common form).

Across five continents and despite a wide variety of screening programmes, women infected with HPV types 16, 18, and 45 were diagnosed with cervical cancers an average of 4 years earlier than women with other high-risk HPV types.

Current vaccines prevent infection by HPV types 16 and 18, and through cross protection partially HPV 31 and 45... The authors say: "Our findings of the early presentation of cases of invasive cervical cancer that were positive for HPV 45 suggest that this genotype should be considered in type-specific screening protocols and that women who are positive should be offered closer surveillance."

The researchers also identified rare HPV types (26, 30, 61, 67, 69, 82, and 91) in tumours as single infections, confirming their contribution to cervical cancer cases worldwide as small (about 1%).

They conclude: "This international effort...reinforces the rationale for prevention of cervical cancer through use of existing vaccines. Our results show which HPV types should be given priority when the cross-protective effects of current vaccines are assessed, and are useful for the formulation of recommendations about the use of second-generation polyvalent HPV vaccines."

In a Comment, Cosette Wheeler from the University of New Mexico Health Sciences Center, USA, says that although the findings largely confirm results of previous smaller studies: "the international effort must be recognised as a Herculean effort that might be the benchmark for all time. The combined data clearly support future directions for cervical screening and type-specific triage, establish the potential worldwide impact of current HPV vaccines, and set priorities for next-generation vaccines."

She adds: "Future HPV genomics and biomarker research...will be important to elucidate the molecular basis of increased carcinogenicity suggested by the HPV-genotype rank order reported in this study of worldwide invasive cervical cancer."

Source: The Lancet