The most cost-effective strategy for human papillomavirus (HPV) vaccination and screening would initiate vaccinations at age 12, followed by cytology screening for HPV every 3 years beginning at age 25, according to the results of a new computer-based modeling study. This approach would reduce mortality due to cervical cancer by 94 percent compared with no intervention at all, concluded the study's authors, Dr. Sue J. Goldie from the Harvard School of Public Health and colleagues, in the April 21 Journal of the National Cancer Institute.

In the study, the cost-effectiveness of various vaccination strategies for two of the most oncogenic HPV strains (16 and 18) and screening - alone and in combination - were examined. All vaccinations were begun at 12 years of age; screenings began at 18, 21, 25, 30, or 35 years of age, with screening intervals ranging from 1 to 5 years. The researchers modeled varying effectiveness of the vaccines ranging from 70 percent to 100 percent. The next most cost-effective strategy, which resulted in an 89.7 percent reduction in mortality, involved a combination of vaccination with screening every 5 years beginning at age 21.

Vaccination at 12 years of age would allow for a later age of screening initiation and less frequent screening intervals than are currently recommended, the authors concluded. Under current U.S. Preventive Services Task Force recommendations, a woman should begin cervical cancer screening 3 years after she begins having sexual intercourse, but no later than age 21; subsequently women should be screened at least once every 3 years.

Persistent HPV infection is the major cause of cervical cancer, and HPV DNA has been found in more than 99 percent of all cervical cancers. Although there are more than 100 strains of HPVs, 4 strains - HPV 16, 18, 45, and 31 - account for about 75 percent of all of the cervical cancers diagnosed each year.

Researchers have been developing and studying the efficacy of HPV vaccines against these high-risk strains. Although no HPV vaccines have been approved by the U.S. Food and Drug Administration, data from clinical trials have produced encouraging results. An 18-month placebo-controlled phase II clinical trial of an HPV 16 vaccine, for example, demonstrated 100 percent efficacy in preventing persistent HPV 16 infection and associated cervical lesions.

With phase III clinical trials underway for both HPV 16 and HPV 18 vaccines, many researchers are investigating how best to implement a combined strategy of primary vaccination against HPV and secondary screening for prevention of cervical cancer.

"While phase III trials provide valuable information about the short-term efficacy of vaccination on HPV infection, decades of follow-up would be necessary to directly observe the ultimate impact of vaccination on cervical cancer mortality," said Dr. Martin Brown, chief of NCI's Health Services and Economics Branch. "The complex trials designed to evaluate combination programs of vaccination and subsequent testing regimens would be logistically infeasible and prohibitively expensive."

Computer-based mathematical modeling, the study authors explained, "can be a useful tool, in conjunction with vaccine efficacy trials, to incorporate data from multiple sources, to extrapolate clinical and economic data beyond the time horizon of a clinical study, to evaluate more strategies than are possible in a single clinical trial, and to assess the relative costs and benefits of alternative policies (screening and/or vaccination) in reducing mortality from cervical cancer."

"Studies such as this one," cautioned Dr. Brown, "try to extrapolate based on currently available data, and there is always a degree of uncertainty about their conclusions."

The authors noted several quantitative limitations to this work; however, a study using a different model, published last year in the Journal of the American Medical Association, reached the same general conclusions about an HPV vaccination and screening strategy.