Advisers to the U.S. Centers for Disease Control and Prevention are considering recommending that the agency extend the recommended HPV vaccination age to cover people beyond age 26 — but public health experts working on their behalf found that the vaccine is not cost-effective for men or women above that threshold.

Led by Jane J. Kim, a professor of health economics at Harvard University, the research published March 11 in PLOS Medicine details all methods and outcomes of the many clinical analyses conducted by the experts working for the Advisory Committee on Immunization Practices, which advises the CDC. The group concluded that HPV vaccination over the age of 26 provides limited health benefits at high cost.

"Cost-effectiveness is meant to provide information on value for money. In this analysis, it is conducted from a health care sector perspective," said Kim, conveying that the high cost is irrespective of payer or state.

Human papillomavirus is a sexually transmitted disease that can sometimes lead to cancer. According to the CDC, nearly 80 million Americans are currently infected with HPV, and every year it causes about 36,000 cases of cancer.

Because of the possible drastic outcomes of HPV, the CDC has been deliberating increasing the age limit for the vaccine. Currently, it only urges that children aged 11 or 12 receive it, and the agency considers immunization a good option up until the age of 26. The American Cancer Society also does not recommend the vaccine after the age of 26.

The team reached its conclusion through model-based analysis that looked at the HPV transmission rate among people up to 45 years old, and potential burden of disease for HPV-related cancers. The models projected lifetime costs, benefits and overall cost-effectiveness of vaccination in the older individuals.

To do this, the researchers included inputs such as historical and future vaccination uptake and HPV-related cancer outcomes. Cost-effectiveness was determined by calculating cost per quality-adjusted life year, or QALY, a concept used by economists to measure disease burden from a cost viewpoint. A value of one equals one year of life in perfect health; a value of zero means one is dead. 

"Although there is no consensus on what threshold of cost per QALY represents a cost-effective intervention," Kim said, "we used commonly cited values ranging from $50,000 to $200,000 per QALY gained as benchmarks for contextualizing our findings."

Kim and her team compared an individual gaining a quality-adjusted life year of one with the cost of intervention that would provide that gain. After modeling the trends, the price raised to about $315,000 to $440,600 per QALY gained for individuals up to 45. However, the QALY system has its flaws. For example, a life of perfect health, or value of one, is technically a subjective matter.

"While we were not surprised by the finding that the cost-effectiveness of HPV vaccination diminishes as the upper age limit is extended beyond age 26 years," said Kim, "we did not know how robust the findings were across the varying assumptions and sensitivity analyses."

There are many commonly held hesitations with model-based research, particularly in terms of bias or confounding variables. The research team made sure to cross-check the results by running sensitivity analyses, but the results remained mostly consistent. 

"All model-based analyses are subject to limitations in their ability to incorporate the best available data, which are still imperfect, while making assumptions about future behaviors and trends," Kim explained. "We guard against these limitations by conducting a range of sensitivity analyses and scenario analyses."

The testing considered the varying vaccine prices and potential "lag time" from HPV infection to development of non-cervical cancers. One of the most important factors studied was compliance with cervical cancer screening; such screening was a huge reason for why immunization is less necessary as people get older. Potential non-compliance posed a negligible issue. 

The sensitivity analysis "gives us more confidence in our conclusions that HPV vaccination past age 26 years is not good value for money," Kim said.

Kim hopes her team's data-based evidence that the age limit is best unchanged, from a monetary value perspective, can also help inform policymakers worldwide. As of 2019, the HPV vaccine was offered in 100 countries.

"In addition to the U.S. guidelines set by the ACIP and CDC, we hope that this analysis will help guide decision-making in other countries that are considering extending the HPV vaccination age limit," she said.

Going forward, Kim plans to examine the need for vaccination among older women with possibly lower dosages in other countries.

She added, "Although this analysis focuses on HPV vaccination, we must not lose sight of the importance of cervical cancer screening among adult women as an effective and cost-effective prevention strategy against cervical cancer, especially among women who are past the age of HPV vaccination."

The study, "Human papillomavirus vaccination for adults aged 30 to 45 years in the United States: A cost-effectiveness analysis," published March 11 in PLOS Medicine, was authored by Jane J. Kim, Stephen Sy, Catherine Regan and Emily A. Burger, Harvard University; and Kate T. Simms, James Killen, Megan A. Smith and Karen Canfell, Cancer Council New South Wales.