NCI Acting Director: Equitable Precision Medicine Requires Concerted Implementation Efforts

Despite significant advances in cancer treatment, molecular sequencing and enrollment of Black patients in clinical trials are still less than that of White and Asian patients.

Health disparities have come to the forefront of health care discourse in a significant way since the start of the COVID-19 pandemic, explained Douglas R. Lowy, MD, principal deputy director and acting director of the National Cancer Institute (NCI) at the National Institutes of Health (NIH) and chief of the Laboratory of Cellular Oncology in NCI’s Center for Cancer Research. Lowy explored this issue during a presentation at the 15th American Association for Cancer Research Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved. Lowy is also an inventor of the human papillomavirus (HPV) vaccine.

“COVID-19 showed front and center the disproportion to which COVID-19 affected people from underrepresented minorities. In addition, George Floyd's murder occurred, and I think the 2 together, plus a lot of other factors, have really put disparities in general and health disparities in particular front and center,” Lowy said during his keynote presentation.

Over the past 20 years, cancer mortality rates have gone down faster in Black males than in any other racial or ethnic group. However, Lowy noted that the data show Black men and women continue to have the highest rate of cancer mortality despite this decrease in incidence. Specifically, uterine cancer mortality rates are the highest in the United States in Black women.

“[Black women are] twice as likely to die of uterine cancer compared to other racial and ethnic groups, and most of the mortality increase is attributable to non-endometrioid uterine cancer, which disproportionately affects Black women, and now Hispanic women as well,” Lowy said. “Mortality has increased 3.5% per year between 2010 and 2017 for Black women and over 6% for Hispanic women. There is an urgent need for new research in affected populations.”

However, Lowy explained that there have been significant strides in the development of new lung cancer treatments, as the rates of lung cancer have gone down faster with mortality than with incidence. Specifically, the incidence of lung cancer has decreased approximately 2.4% per year over the past 5 years, whereas the mortality rate has decreased by 4.6% annually.

“It’s really important to recognize that we have made a lot of advances in cancer treatment. The issue is [whether] everybody is going to benefit equitably from those advances,” Lowy said. “It's estimated that about 50% of patients with lung cancer have an actionable mutation, so that there is treatment available for their mutations. These data are really extraordinary. Although somewhat out of date, I can assure you that qualitatively they reflect what continues to happen today.”

However, despite these significant advances in the treatment of lung cancer, Lowy explained that the molecular sequencing of Black patients with lung cancer is substantially less than that of White patients and Asian patients.

“So the call out here is that equitable precision medicine requires concerted implementation efforts,” Lowy said.

Furthermore, despite the increase in attention paid to this issue in recent years, Lowy noted that an international immunotherapy trial published approximately 2 years ago had an almost negative level of enrollment for Black patients who participated in the trial.

“It really is extraordinary, and it's very difficult to say that this has now been tried in a widespread population,” Lowy said. “I'm pleased to say that with Black patients who are treated with immunotherapy, they seem to do as well as White patients. But it really is a shame that they were not included [in this trial].”

Lowy noted that when looking at the data, it becomes clear that the country still has a long way to go in its work to address health disparities for underrepresented minorities throughout the country, despite significant advancements in cancer treatments more broadly.

“I've taken this from the first lines of ‘A Tale of Two Cities’ by Charles Dickens, ‘It was the best of times, and it was the worst of times,’” Lowy said. “I really think this exemplifies where we are now.”

Lowy noted that cervical cancer data in particular exemplifies this quote. Specifically, between 2000 and 2019, age-adjusted incidence for cervical cancer in Black women went down somewhat. However, in White women, the incidence rate started at a much lower rate and stayed steadily at approximately the same lower rate over the 2-decade period, while incidence in Hispanic women went down for the first decade before leveling off in the second.

Lowy noted that the disparities in the rates of cervical cancer really become apparent in mortality rates. Lowy explained that Black women have a mortality rate from cervical cancer that is about 50% higher than that of White women, while Hispanic women are in-between the rates of Black and White women. Additionally, mortality rates for American Indian, Alaska Native, Asian, and Pacific Islanders are approximately the same if not a little bit lower than that of White patients.

However, Lowy explained that data from Africa on rates of cervical cancer incidence may shed some light on these data from the United States. Specifically, the rates of cervical cancer incidence in Africa are approximately 4 times higher than that of the United States, whereas rates of mortality from cervical cancer are 6 times higher.

Additionally, 90% of cervical cancer cases and deaths occur in low- and middle-income countries, Lowy noted.

“This is projected to increase by about 2% per year,” Lowy said. “The good news is we have a lot to offer. [There is] vaccination for primary prevention, and cervical cancer screening for secondary prevention. Also, soon we will have anal cancer screening, at least I expect it will become standard of care because of the positive results of the ANCHOR study.”

In addition to prevention methods, there are also treatments of invasive cervical cancer available that have shown efficacy in saving lives, Lowy explained. Further, the data show that when early-stage cervical cancer is treated appropriately, 5-year survival is at approximately 90%.

For cervical cancer prevention, Lowy and his colleague John Schiller, PhD, deputy chief of the Laboratory of Cellular Oncology, led the initial development, characterization, and clinical testing of the preventive particle-based HPV vaccines that are now used in 3 FDA-approved HPV vaccines (Gardasil, Merck Sharp & Dohme Corp; Gardasil 9, Merck & Co; Cervarix, GlaxoSmithKline Biologicals).

“We thought that it was going to be able to prevent cervical cancer,” Lowy said. “Now, several countries which adopted HPV vaccination on a nationwide basis are showing that women who were vaccinated when they were 16 years or younger—this is in Denmark—have about a 90% decrease in their development of cervical cancer.”

However, data from nationwide HPV vaccinations have also shown that women who were vaccinated between 20 and 30 years of age show no obvious decrease in their risk of developing cervical cancer, at least in the first 15 years following vaccination. Lowy also noted that the data do demonstrate benefit in vaccinating women between 20 and 30 years of age, but the real benefit of vaccination is present if women are vaccinated before becoming sexually active.

“The vaccine works well for preventing new infection, but it doesn't really do anything to alter the natural history of established infection,” Lowy said.

To this end, Lowy explained that health care providers have a pivotal role in recommending vaccination to women aged 16 years or younger, for whom the greatest benefit of getting vaccinated against HPV would occur, as well as for women between 20 and 30 years of age, for whom moderate benefit would occur.

Earlier this year, CDC data were released showing an uptake of HPV vaccination in patients for whom a health care provider made an HPV vaccination recommendation. Overall, the data showed that uptake of HPV vaccination was significantly higher among patients who were recommended to get it by a health care provider versus those who did not get a recommendation by a health care provider.

“This just shows how powerful our voices can be—the voices of health care providers. I mean, I'm showing it for HPV, but it is true of many other situations as well,” Lowy said.

In low- and middle-income countries, Lowy noted that the reality currently is that only approximately 10% of eligible young women have gotten vaccinated each year. In the United States, although not a high HPV vaccination adopter initially, the CDC data published this year indicated that 76% of teenagers aged 13 to 17 years have gotten at least 1 dose of the HPV vaccine. In addition, there has been a lot of herd immunity from the vaccine in the United States as well, Lowy explained.

“So I think we can look forward to real improvement in the United States. It would be great to have vaccination rates even higher, but there's been a lot of progress, thanks to publicity from cancer centers, publicity from the CDC, and in many other areas,” Lowy said. “What we are thinking about at the NCI is to further reduce the number of doses—it's not yet FDA-approved, but we've developed a lot of evidence that 1 dose of the HPV vaccine seems to provide at least 11 years of protection, which is as far as we've gone with our Costa Rican vaccine trial.”

Also, Lowy noted that data from the trial showed that the antibody levels also stayed essentially level throughout those 11 years following going down a bit after the first couple of months.

“So we are cautiously optimistic that 1 dose will actually be successful, and this could be a way of getting more vaccines into more arms,” Lowy said. “To try to do something on a global scale, you need to think about vaccinating at least 40 million women in each birth cohort. And I'm focused on women, largely because in lower- and middle-income countries, cervical cancer is far and away the biggest problem. Second, because of the sexual transmission of HPV infection, vaccinating one gender is sufficient.”

Reference

Lowy DR. Ending cancer as we know it – For all. Philadelphia, PA: 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; September 16, 2022.