Clinical laboratories can play a role in educating and advising at-home self-collection test users
Women are twice as likely to follow through with cervical cancer screening when they receive a self-collection kit for HPV infection rather than a reminder phone call from a clinical laboratory. That’s according to research conducted at University of Texas MD Anderson Cancer Center.
Human papillomavirus (HPV) causes nearly all types of cervical cancer. In their study, the researchers found that 41% of women pursued cancer screening when given a self-collection kit as opposed to 17% who only received a telephone reminder.
According to a University of Texas press release, MD Anderson conducted its study between February 2020 and August 2023 and included 2,500 women from the Houston area between the ages of 30-65. Most of the women (94%) were racial or ethnic minorities, and 56% of the participants received help from a publicly funded financial assistance program. More than 80% of the women in the self-collection groups returned their self-collection kits.
“As self-collection tests become available in the US, it’s vital that we gather data to guide how they are rolled out. We want to make sure that they become available in clinics and health centers that care for people who often have the hardest time accessing healthcare,” said Jane Montealegre, PhD, associate professor in the Department of Behavioral Science, Division of Cancer Prevention and Population Sciences at the University of Texas.
“By removing barriers, we are hopeful that we can improve the uptake of evidence-based screening tests and make significant progress against this preventable disease,” said Jane Montealegre, PhD, associate professor in the Department of Behavioral Science, Division of Cancer Prevention and Population Sciences at the University of Texas, in the press release. (Photo copyright: University of Texas.)
Comfortable Alternative to Pap Smears
At-home cervical cancer screening tests are becoming more popular as opposed to the Pap smear, a gynecological procedure that can be painful or uncomfortable for some patients.
In May, Teal Health announced it had received FDA approval to distribute its Teal Wand, the first at-home cervical cancer screening self-collection device commercially available, according to G2 Intelligence, a sibling publication to Dark Daily.
The turnaround time for the test is about one week, Teal spokesperson Lilly Bromberg told G2. Results are reported in a secure patient portal. Teal clinicians will schedule a follow-up with any patient who has abnormal results to explore future steps.
Option for Demographics More Likely to Develop Cervical Cancer
These self-collection tests could also reach patients who are unable to access care. “Too many women—especially those who are uninsured, live in rural areas, or come from marginalized and underserved communities—aren’t getting screened for cervical cancer,” said Montealegre.
Cervical cancer affects nearly 13,000 women annually, and racial disparities exist amongst those affected. According to the American Journal of Preventative Medicine, black women in America are 30% more likely to develop cervical cancer, and 60% of them are more likely to die of the disease, than non-Hispanic white women. Hispanic women have a 51% higher chance of developing cervical cancer than non-Hispanic white women.
At-home screening may be a crucial next step in closing the gaps in care and further driving down the rates of cervical cancer. The findings of this study show how the convenience and ease of these tests may be able to bring at-risk women closer to diagnosis and treatment of cervical cancer.
As newly approved self-collection tests become more popular, there may be a growing market for clinical laboratory professionals to advise at-home test users on their functionality and the results they return. Self-collection testing may increase in years to come because of these advances.
Study is first solid evidence that introduction of HPV vaccines may be a factor in the reduction in rates of cervical cancer among those who were vaccinated nearly 20 years ago
This success story confirms that a better understanding of what causes cervical cancer—when combined with the development of clinical laboratory tests that detect the HPV virus—were key developments in the fight against this deadly disease.
The study, led by cancer population scientist Ashish Deshmukh, PhD, epidemiologist, professor of public health sciences and co-leader of the cancer control program at the Hollings Cancer Center (HCC) at MUSC, found the connection between the decline in cervical cancer rates and the adoption of the HPV vaccine.
Pathologists and clinical laboratory managers will want to monitor the worldwide effort to eradicate cervical cancer, as many countries focus their efforts on HPV vaccine compliance. The scientists published their findings in the Journal of the American Medical Association (JAMA) titled, “Cervical Cancer Mortality among US Women Younger than 25 Years, 1992-2021.”
“We had a hypothesis that since it’s been almost 16 years, that maybe we might be starting to see [the] initial impact of HPV vaccination on cervical cancer deaths, and that’s exactly what we observed,” Ashish Deshmukh PhD (above), epidemiologist and professor of public health sciences at Medical University of South Carolina in Charleston, told Science News. The MUSC study provides important findings for clinical laboratories and anatomic pathologists providing vaccinations against Human Papillomavirus. (Photo copyright: Medical University of South Carolina.)
MUSC Study Details
Deshmukh’s team examined cervical cancer mortality rates of women younger than 25 from 1992-2021. The team divided data into 3-year periods, noting a “gradual decline in cervical cancer deaths of almost 4%” which brought deaths to .02 per 100,000 people from 2013-2015, Science News reported, adding that the researchers speculated that the “steady drop might be due to improved prior prevention and screening methods for cervical cancer.”
The death rate for cervical cancer continued to trend downward with “a dramatic reduction in mortality over just 60%,” arriving at .007 deaths per 100,000 according to the 2019-2021 data, Science News continued.
In their JAMA article, the MUSC researchers noted a continued positive shift toward lower cervical cancer rates beyond 2021, with a 12% per year decline and 65% reduction overall.
“They’re seeing this precipitous drop in mortality at the time that we would be expecting to see it due to vaccination,” Emily Burger, PhD, professor at the University of Oslo and research scientist at Harvard T.H. Chan School of Public Health told Science News. “Ultimately, we hope we are preventing mortality and death [with the introduction of vaccines], and this study is really supporting that conclusion.”
Nonetheless, a definitive connection to the HPV vaccine was not possible to determine “because it’s unclear whether the women in the study cohort were, in fact, vaccinated,” Science News reported.
Development of the PAP Smear
Cervical cancer was first discovered in 1886. At that time pathologists relied on “examination of tissue biopsies derived from an observable lesion,” LabTAG noted. It was George Papanicolaou, PhD—considered to be the father of cytology—who determined in 1943 that more could be observed via a surface biopsy under a microscope. The Pap Smear was born.
The Pap Smear, for which wider screening began in the US in the late 1950s and 1960s, began to reduce deaths from cervical cancer by the 1990s. But women who did not get an annual pap were the ones generally to be diagnosed with advanced cervical cancer.
By the 1990s, pap smear testing was a major business for clinical laboratories and pathology groups. Fifty-five million pap tests were done annually in the 1990s.
In 2004, clinical laboratories began HPV testing. Then came the HPV vaccine. Introduced in 2006, HPV vaccine programs focused on 12-15 year-old girls with hopes of preventing cervical cancer.
Clinical laboratories in the US today perform many fewer Pap smear tests.
While efforts overseas appear to focus on HPV vaccine requirements, the US has been hesitant to do the same. The District of Columbia, Hawaii, Virginia, and Rhode Island are the only states to require it by grade seven, Immunize.org notes. Various reasons have kept it from being required in the US, including fear that it might encourage sexual activity in teens.
There is hope that, with a larger focus on cervical cancer, more deaths can be prevented since the cancer itself is slow growing. “When we look at HPV vaccination coverage in the US, we haven’t reached our goal. We have to do better in terms of improving vaccination rates,” Deshmukh told Science News.
As scientists continue to gain a better understanding of causes and prevention of cervical cancer, new clinical laboratory tests may be developed to detect HPV. Thus, lab managers will want to stay in touch with current research as it will surely impact the testing performed by labs in the future.
Proof-of-concept study may eventually lead to new clinical laboratory urine tests for fast, non-invasive detection of cancer
Here is the latest example of researchers finding useful biomarkers in urine for diagnosing certain cancers. The discovery comes from the University of Michigan Health Rogel Cancer Center, where, in a proof-of-concept study, scientists developed a urine-based test that screens for circulating free DNA (cfDNA) fragments (aka, cell-free DNA) released by tumors in the head and neck. If they confirm these findings, it’s possible the technology could be adapted into a non-invasive clinical laboratory test for selected cancers.
One such cancer is human papillomavirus (HPV) which, though “widely recognized for causing cervical cancer” is “increasingly found to cause cancers in the mouth, throat, and other head and neck regions,” according to a U-M Medical School press release.
The U-M study findings could lead to an early, non-invasive test for the detection of cancer, as compared to traditional urine or blood-based liquid biopsy testing.
“In this study, we provide evidence to support the hypothesis that conventional assays do not detect ultrashort fragments found in urine since they are designed to support longer DNA fragments. Our team used an unconventional approach to develop a urine test for HPV-positive head and neck cancer ctDNA detection,” said Chandan Bhambhani, PhD (above), Research Lab Specialist Intermediate at University of Michigan and co-first author of the study, in a news release. Clinical laboratories may soon have a new urine-based test for detecting cancer. (Photo copyright: LinkedIn.)
According to the researchers, benefits of urine testing include:
Testing with urine is convenient for people who may be unable to access healthcare and phlebotomy services.
Urine has low biohazard risk and may be easily collected in large amounts, compared with blood.
Ongoing collection of urine could make way for TR-ctDNA “kinetics to be used as a high time-resolution biomarker” to monitor patients’ response to treatment.
However, urine, the researchers cautioned, must be analyzed in a different manner if it is to be comparable in efficiency to blood-based ctDNA testing.
“There have been mixed reports on the efficiency of TR-ctDNA detection compared with that of blood ctDNA. A potentially crucial factor for the analysis of TR-ctDNA is knowing the length of TR-ctDNA fragments present in urine, because this affects assay design for optimal sensitivity in TR-ctDNA detection,” the researchers explained.
New Assay Detects Ultrashort DNA Fragments
To complete their study, the U-M researchers developed an ultrashort HPV droplet digital PCR (polymerase chain reaction) assay that enabled detection of TR-ctDNA from HPV-associated oropharyngeal squamous cell carcinoma (HPV OPSCC), BioTechniques reported.
The assay was made to target the HPV16 E6 (Human papillomavirus 16) gene and to measure TR-ctDNA in patients with HPV OPSCC, the JCI Insight paper noted.
“The HPV16 E6 gene represents a highly recurrent ctDNA target in the population of patients with HPV OPSCC,” the researchers wrote in JCI Insight, adding:
Targeting ultrashort fragments was essential “for robust TR-ctDNA detection.”
Results in urine with patients with HPV OPSCC was consistent with results from plasma ctDNA.
The test, still in the discovery phase, was mailed to patients who were being treated for the disease and who reside within 100 miles of Ann Arbor, Mich. They returned urine samples for testing at the U-M lab and to get insights into possible post-treatment needs.
“Using longitudinal urine samples from a small case series, we showed proof of concept for early detection of cancer recurrence. Thus, our results indicate that by targeting ultrashort DNA fragments, TR-ctDNA becomes a viable approach for HPV OPSCC detection and potentially for cancer recurrence monitoring after treatment,” the authors wrote.
Further Studies, Possible Test Expansion
HPV infection—and especially HPV type 16—is a growing risk factor for oropharyngeal cancers, according to the National Cancer Institute.
The U-M Rogel Cancer Center scientists plan more studies to leverage the information urine may carry about an individual’s health. The researchers intend to expand the scope of their new test to other cancers including breast cancer and acute myeloid leukemia.
“The test that has been developed has detected cancer far earlier than would typically happen based on clinical imaging. As such, these promising results have given us the confidence to broaden the scope of this study, seeking to expanding distribution even further,” said J. Chad Brenner, PhD, Associate Professor of Otolaryngology-Head and Neck Surgery, U-M Medicine, and co-senior author of the study, in the news release.
The University of Michigan Health study exemplifies scientists’ commitment to new categories of biomarkers that can be used for medical laboratory tests and prescription drugs. And by focusing on urine, the researchers made it possible for patients to collect specimens themselves and send them to the medical laboratory for analysis and reporting.
Even US military clinical laboratories strive to cut costs, protect quality, and improve outcomes
Defense Health Agency (DHA), a part of the federal Department of Defense (DOD), recently launched a plan to consolidate healthcare facilities within certain geographical regions and to unify and integrate the military’s clinical laboratory operations in those areas. The goal is to streamline efficiencies and lower costs while maintaining quality lab testing services.
The DOD operates a nationwide network of medical treatment facilities (MTFs) that include state-of-the-art clinical and anatomic pathology laboratories serving military personnel and their families. These military labs face the same issues of cost, efficiency, and outcomes as do civilian clinical laboratories throughout the United States.
To address those challenges and bring together clinical laboratory services in specific regions, the DHA established the Tidewater Market in April of 2021 to serve select US Air Force, Army, and Navy MTFs in the Washington DC metro area, central North Carolina, Jacksonville, and coastal Mississippi.
Tidewater is the fifth Military Health System (MHS) market created to manage MTFs as they transition into the DHA.
Health.mil—a website maintained by the MHS as an informational resource for those it serves—describes the MHS as “one of America’s largest and most complex healthcare institutions, and the world’s preeminent military healthcare delivery operation.
“Our MHS saves lives on the battlefield, combats infectious disease around the world, and is responsible for providing health services through both direct care [at military hospitals and clinics known as ‘military treatment facilities’] and private sector care to approximately 9.6 million beneficiaries, composed of uniformed service members, military retirees, and family members,” Health.mil notes.
With 9.6 million beneficiaries, MHS is one of the largest healthcare service organizations operating in the United States.
“The establishment of this market provides a true opportunity to optimize healthcare for our beneficiaries by focusing on outcomes and access across the Tidewater market,” said Navy Rear Admiral Darin Via, MD, Tidewater market manager, in an MHS/DHA news release. “It also allows us to work towards standardization of processes, creating an easier environment for our patients to navigate within.” (Photo copyright: US Navy.)
Finding Efficiencies, Optimizing Clinical Laboratory Processes and Services
In an article outlining the Tidewater Market clinical laboratory initiative, Health.mil noted that “A market is a group of MTFs in one geographic area working together with its TRICARE partners, Veterans Affairs hospitals, other federal healthcare organizations, private sector teaching hospitals and medical universities, as well as other healthcare partners. Markets operate as a system to support the sharing of patients, staff, budget, and other functions across facilities to improve readiness and the delivery and coordination of health services.”
The Tidewater Market provides integrated, affordable, high-quality healthcare services to active-duty service members, military retirees, reservists and national guardsmen, and their families. The market currently serves more than 390,000 beneficiaries.
In 2022, the Tidewater Market Laboratory/Pathology Integration Working Group was created to optimize services while reducing costs within the market. The group was created by US Navy Captain Stacie Milavec, who has more than 23 years of experience in military medicine.
“One of DHA’s goals with setting up a market structure is to find efficiencies and optimize and standardize processes and services wherever possible,” Milavec said in an MHS/DHA news release. “We’ve been able to do exactly that by collaborating within our working group.”
Resource Sharing between Military Clinical Laboratories
The MTFs that are geographically close to each other helped expedite turnaround times for testing results. By working together, they saved the Tidewater Market an estimated $80,000 during fiscal year 2022.
One of the methods they used to streamline testing and lower costs was to allow resource sharing between facilities within the market. For example, the full-service clinical laboratory located at the Naval Medical Center Portsmouth (NMCP) began performing head and neck pathology cases, breast biopsies, and PAP testing for some of the other facilities within the Tidewater Market. These services were previously performed by other means and in some cases were sent to commercially-contracted clinical laboratories for analysis at a high cost.
The NMCP also took on Human Papilloma Virus (HPV) testing for all MTFs within the market.
In February of 2023, NMCP began taking on additional clinical chemistry tests from the 633rd Medical Group at Joint Base Langley-Eustis located in Hampton, Virginia. Prior to that collaboration, those tests were sent out to contracted labs off-base for analysis.
“[Through collaboration between the MTFs] we’ve been able to successfully transition civilian marketplace send-out testing back into the military market by utilizing market resources,” said pathologist US Air Force Captain Dianna Chormanski, MD, Laboratory Medical Director with the 633rd Medical Group at Joint Base Langley-Eustis, in the press release. “I’m a big fan of cooperation and working together, and that’s what a market should be.”
The DHA established the market-based structure as part of the National Defense Authorization Act for Fiscal Year 2017. It’s an example of regional laboratory consolidation within one region of the US where a common effort brought together clinical laboratories operating on military bases of different services. The military’s goal was a unified, integrated medical laboratory operation that could deliver targeted cost savings while maintaining quality lab testing services. It appears to be successful.
CDC estimates that 92% of cancers caused by HPV could be eliminated in the US if HPV vaccination recommendations in this country are followed
Medical
laboratories in the United States once processed as many as 55-million Pap tests each year. However,
the need for cervical cancer screening tests is diminishing. That’s primarily because
the human
papilloma virus (HPV) vaccination effectively eliminates new cases of
cervical cancer. At least, that’s what’s happening in Australia.
When it was introduced in 2007, Australia’s nationwide
publicly-funded HPV
vaccination program only included girls, but was extended to boys in 2013.
Today, it is being credited with helping slash the country’s cervical cancer
rates.
Research published in The
Lancet Public Health (Lancet) predicts cervical cancer could be
eliminated in Australia by 2028 if current vaccination rates and screening
programs continue. Cervical cancer would be classified as effectively
eliminated once there are four or fewer new cases per 100,000 women each year.
These developments will be of interests to pathologists and cytotechnologists in
the United States.
“From the beginning, I think the [Australian] government
successfully positioned the advent of HPV vaccination as a wonderful package
that had a beneficial effect for the population,” Karen
Canfell, PhD, Director, Cancer Research Division at Cancer Council New
South Wales, Australia, and Adjunct Professor, University
of Sydney, told the Texas
Tribune. “It was celebrated for that reason, and it was a great public
health success.”
In addition to high vaccination rates, the Lancet
study notes that last year Australia transitioned from cytology-based cervical screening
every two years for women aged 18 to 69 years, to primary HPV testing every
five years for women aged 25 to 69 and exit testing for women aged 70 to 74
years.
“Large-scale clinical trials and detailed modelling suggest
that primary HPV screening is more effective at detecting cervical
abnormalities and preventing cervical cancer than screening with cytology at
shorter intervals,” the Lancet study states.
The incidence of cervical cancer in Australia now stands at
seven cases per 100,000. That’s about half the global average. The country is
on pace to see cervical cancer officially considered a “rare” cancer by 2020,
when rates are projected to drop to fewer than six new cases per 100,000 women.
US Cervical Cancer Rates
In Texas, meanwhile, the state’s failure to embrace HPV
vaccination is being blamed for slowing potential improvements in cervical
cancer rates. In 2007, Texas lawmakers rejected legislation that would have
mandated girls entering sixth grade be vaccinated for HPV. The Texas Tribune
reports that, in the decade that followed, vaccination rates remained stagnant
with only about 40% of Texans between 13 and 17 years old having been vaccinated
for HPV by 2017.
Though Texas has a similar size population as Australia, the
state’s low vaccination rates have meant cervical cancer rates have shown
little improvement. Statistics compiled by the federal Centers for Disease Control
and Prevention (CDC) show that Texas’ age-adjusted rate of new cervical
cancer cases sits at 9.2 per 100,000 women—unchanged since 2006.
Texas has the fifth highest rate of cervical cancer in the
nation, according to the CDC.
Texas State Rep. Jessica Farrar, a Democrat from Houston, maintains Texas should have followed the example of Australia, which in 2007 began a publicly funded HPV vaccination program that has the country on the verge of eliminating cervical cancer by 2028. Texas rejected mandatory HPV vaccinations and now has one of the highest cervical cancer rates in the US. “This is a preventable disease, and we should and can be doing more,” she told the Texas Tribune. “Here we are 12 years later, and look where we could’ve been, but because of certain beliefs, we’re suffering from cancers that could have been avoided.” (Photo copyright: The Texas Tribune.)
Lois Ramondetta,
MD, Professor of Gynecologic Oncology at MD Anderson Cancer Center in Houston,
told the Texas Tribune the state ignored an opportunity that Australia
seized. “[Australia] embraced the vaccine at that time, and our fear kind of
began around then,” Ramondetta said. “Really, vaccination in general has just
gone down the tube since then.”
CDC Study Pushes HPV Vaccination Recommendations in US
Texas is not the only state failing to capitalize on the HPV
vaccine’s cancer-curing promise. The CDC recently stated in a news
release announcing a recent study that 92% of cancers caused by HPV could
be eliminated if HPV vaccine recommendations were followed. CDC published the
study in its Morbidity
and Mortality Weekly Report.
HPV is a common virus that is linked to not only cervical
cancer but also cancers of the penis, head, and neck, as well as conditions
like genital warts. Though the CDC recommends children get the two-dose vaccine
at ages 11-12, the study findings indicate that only 51% of teens ages 11 to 17
have received the recommended doses of HPV vaccine, a 2% increase from 2017 to
2018.
“A future without HPV cancers is within reach, but urgent
action is needed to improve vaccine coverage rates,” Brett
Giroir, MD, Assistant Secretary for Health, US Department of Health and
Human Services (HHS), stated in the CDC news release. “Increasing HPV
vaccination overage to 80% has been and will continue to be a priority
initiative for HHS, and we will continue to work with our governmental and
private sector partners to make this a reality.”
Can Australia Eliminate Cervical Cancer?
University of Queensland Professor Ian Frazer, MD, who
co-authored the Lancet Public Health study, believes Australia is on the
verge not only of eliminating cervical cancer, but also eradicating the HPV
virus itself.
“Because this human papillomavirus only infects humans, and
the vaccine program prevents the spread of the virus, eventually we’ll get rid
of it, like we did with smallpox,” Frazer told The
Age.
“It’s not going to happen in my lifetime,” he added. “But it
could happen in the lifetime of my kids if they go about it the right way.”
If Australia’s combination of high HPV vaccination rates and
new HPV screening program succeeds in effectively eliminating cervical cancer,
clinical laboratories in this country should expect stepped-up efforts to
increase HPV vaccination rates in the United States. A renewed focus on reducing—and
ultimately eliminating—cervical cancer, could lead to fewer or less-frequently
performed Pap tests as part of cervical cancer screening protocols.
