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.
Endemic in the Amazon region, recent spread of the disease caused the CDC to issue recommendations to travelers who develop symptoms after visiting certain countries
Anatomic pathologists, microbiologists, and clinical laboratories active in infectious disease testing will want to stay informed about the worldwide progression of the Oropouche virus. The infectious pathogen is spreading beyond the Amazon region (where it is endemic) into more populated areas—including the US—and possibly being transmitted in novel ways … including through sexual activity.
The virus primarily spreads to people through biting small flies called midges (a.k.a., no-see-ums), according to a CDC Health Alert Network (HAN) Health Advisory, which added that mosquitoes can also spread the disease.
Oropouche infections, the CDC said, are occurring in Brazil, Bolivia, Peru, Columbia, and Cuba. Cases identified in the US and Europe seem to be among travelers returning from those countries. Reported cases also include deaths in Brazil and cases of mother-to-child (vertical) transmission.
There is “an increase in Oropouche virus disease in the Americas region, originating from endemic areas in the Amazon basin and new areas in South America and the Caribbean,” CDC noted in its Health Advisory.
Though de Oliveira notes that a global outbreak is not yet expected, researchers are nevertheless raising the alarm.
“The challenge is that this is such a new disease that most clinicians—including infectious disease specialists—are not aware of it and we need to make more patients and healthcare providers aware of the disease and increase access to diagnostics so we can test for it,” said David Hamer, MD (above), infectious disease specialist and professor, global health, at Boston University School of Public Health, in an NPR article. “Over the next year, we are going to learn a lot more.” Pathologist, microbiologists, and clinical laboratories will want to keep an eye on the spread of the Oropouche virus. (Photo copyright: Boston University.)
Risks to Pregnant Women, Seniors
Research published in The Lancet Infectious Diseases estimates up to five million people in the Americas are at risk of exposure to the Oropouche virus. The authors also pointed out that cases in Brazil swelled from 261 between the years 2015 to 2022 to 7,497 by August 2024.
About 60% of people infected with Oropouche have symptoms such as fever, chills, headache, muscle aches, and joint pains, according to the CDC Health Advisory, which added that the symptoms generally appear three to 10 days after exposure.
Those with the highest risk of complications from the disease, according to the CDC, include pregnant women, those over age 65, and people with medical conditions such as:
“The geographic range expansion, in conjunction with the identification of vertical transmission and reports of deaths, has raised concerns about the broader threat this virus represents in the Americas,” an additional paper in Emerging Infectious Diseases noted.
“Healthcare providers should be aware of the risk of vertical transmission and possible adverse impacts on the fetus including fetal death or congenital abnormalities,” CDC said in an Oropouche Clinical Overview statement.
“There have been a few cases of maternal to fetal transmission, and there are four cases of congenital Oropouche infections that have been described—all of which led to microcephaly, which is a small head size,” David Hamer, MD, infectious disease specialist and professor global health, Boston University School of Public Health, told NPR.
Diagnostic Testing at Public Labs
Clinical laboratories and physicians should coordinate with state or local health departments for Oropouche virus testing and reporting.
People should consider Oropouche virus testing if they have traveled to an area with documented or suspected cases, have symptoms including fever and headache, and have tested negative for other diseases, especially dengue, according to CDC.
Taking Precautions after Sex
“This [possibility of sexual transmission] brought up more questions than answers,” Hamer told NPR, adding, “we know now is that sexual transmission could happen.”
Though no documented cases of sexual transmission have been recorded, the CDC nevertheless published updated interim guidance, “recommending that male travelers who develop Oropouche symptoms after visiting areas with Level 1 or 2 Travel Health notices for Oropouche to ‘consider using condoms or not having sex for at least 6 weeks’ from the start of their symptoms,” NPR reported.
“Because stillbirths, birth defects, and severe complications and deaths in adults have been reported, CDC is providing interim recommendations on preventing possible sexual transmission based on what we know now,” the CDC stated.
Clinical laboratory leaders working with infectious disease colleagues can help educate physicians and the community about the Oropouche virus and the need to prevent bites from midges and mosquitoes by using, for example, Environmental Protection Agency (EPA) registered insect repellant.
Diagnostics professionals will want to stay abreast of developing Oropouche cases as well as changes to or expansion of clinical laboratory testing and reported guidance.
Researchers used CRISPR-based assays to develop new clinical laboratory point-of-care blood test which boasts accuracy, affordability, and accessibility
According to UPI, the test can “distinguish between influenza A and influenza B—the two main types of seasonal flu—as well as identifying more virulent strains like H1N1 and H3N2.”
Many research teams are working to develop paper-based diagnostic screening tests because of their lower cost to produce and usefulness in remote locations. Should this near-patient point-of-care test become clinically viable, it could mean shorter times to answer, enabling speedier diagnoses and earlier start of treatment.
It also means patient specimens do not have to be transported to a clinical laboratory for testing. And reduced cost per test makes it possible to test more people. This serves the public health aspect of monitoring outbreaks of influenza and other diseases and gives hope for improved treatment outcomes.
“Being able to tease apart what strain or subtype of influenza is infecting a patient has repercussions both for treating them and public health interventions, said Jon Arizti Sanz, PhD, co-lead study author and postdoctoral researcher at the Broad Institute of Harvard and MIT, in a Broad Institute news release.
“Ultimately, we hope these tests will be as simple as rapid antigen tests, and they’ll still have the specificity and performance of a nucleic acid test that would normally be done in a laboratory setting,” Cameron A. Myhrvold, PhD (above), Assistant Professor of Molecular Biology at Princeton University in New Jersey, told CIDRAP. Influenza tests that can be performed at the point of care and in remote locations may reduce the number of screening tests performed by clinical laboratories. (Photo copyright: Michael James Butts/Hertz Foundation.)
Her team developed their tests using Streamlined Highlighting of Infections to Navigate Epidemics (SHINE), “a clustered regularly interspaced short palindromic repeats (CRISPR)-based RNA detection platform,” the researchers wrote in their Journal of Molecular Diagnostics paper.
“SHINE has a runtime of 90 minutes, can be used at room temperature and only requires an inexpensive heat block to heat the reaction. The SHINE technology has previously been used to identify SARS-CoV-2 and later to distinguish between the Delta and Omicron variants,” Bioanalysis Zone reported.
“The test uses genetically engineered enzymes to identify specific sequences of viral RNA in samples,” the researchers told UPI. Originally designed to detect COVID-19, the team adapted the technology to detect influenza in 2022 “with the aim of creating a screening tool that could be used in the field or in clinics rather than hospitals or high-tech diagnostic labs,” they said.
Influenza A and B as well as H1N1 and H3N2 subtypes were the targets of the four SHINE assays. “When tested on clinical samples, these optimized assays achieved 100% concordance with quantitative RT-PCR. Duplex Cas12a/Cas13a SHINE assays were also developed to detect two targets simultaneously,” the researchers wrote in their paper.
The team used “20 nasal swabs from people with flu-like symptoms during the 2020-2021 flu season, nasal fluid from healthy people as the control, and 2016-2021 influenza sequences downloaded from the National Center for Biotechnology Information Influenza (NICB) database. They compared the results with those from quantitative reverse transcription-polymerase chain reaction (RT-PCR) tests,” CIDRAP reported.
The original 2020 test (shown above) takes 90 minutes to develop at room temperature. The test developers aim to drop this down to 15 minutes. In comparison, typical polymerase chain reaction (PCR) testing requires medical laboratories to have specialized equipment, trained staff, and prolonged processing times, the Broad Institute news release notes. (Photo copyright: Broad Institute.)
Implications of the New Tests
The ease of the new tests is an important development since approximately only 1% of individuals who come down with the flu see doctors for testing, according to the news release. And researchers had this in mind, looking at speed, accuracy, and affordability as a means to “improve outbreak response and infection care around the world,” UPI reported.
There are great benefits to strain differentiation that be achieved with the new test. Doctors are hopeful the test will help dial in the best treatment plans for patients since some strains are resistant to the antiviral medication oseltamivir (Tamiflu), UPI noted. This is significant since Tamiflu “is a common antiviral,” said Sanz in the Broad Institute news release.
“These assays have the potential to expand influenza detection outside of clinical laboratories for enhanced influenza diagnosis and surveillance,” the Journal of Molecular Diagnostics paper noted. This allows for more strategic treatment planning.
“Using a paper strip readout instead of expensive fluorescence machinery is a big advancement, not only in terms of clinical care but also for epidemiological surveillance purposes,” said Ben Zhang, an MD candidate in the Health Sciences and Technology at Harvard and co-first author of the study, in the Broad Institute news release.
Future Plans for Tests
“With further development, the test strip could be reprogrammed to distinguish between SARS-CoV-2 and flu and recognize swine flu and avian flu, including the H5N1 subtype currently causing an outbreak in US dairy cattle,” the study authors told CIDRAP.
The team is also looking at ways to help prevent H5N1 from crossing into human contamination, Sanz told UPI.
The new Princeton/MIT/Harvard tests echo the trend to bring in affordability and ease-of-use with accurate results as an end goal. Faster results mean the best treatments for each person can start sooner and may render the transport of specimens to a clinical laboratory as a second step unnecessary.
As research teams work to develop paper-based viral tests for their plethora of benefits, clinical laboratories will want to pay close attention to this development as it can have a big implication on assisting with future outbreaks.
Additional research is needed before these tests are going to be commonplace in homes worldwide, but this first step brings inspiration and hope of what’s to come.
Study results from Switzerland come as clinical laboratory scientists seek new ways to tackle the problem of antimicrobial resistance in hospitals
Microbiologists and clinical laboratory scientists engaged in the fight against antibiotic-resistant (aka, antimicrobial resistant) bacteria will be interested in a recent study conducted at the University of Basel and University Hospital Basel in Switzerland. The epidemiologists involved in the study discovered that some of these so-called “superbugs” can remain in the body for as long as nine years continuing to infect the host and others.
The researchers wanted to see how two species of drug-resistant bacteria—K. pneumoniae and E. coli—changed over time in the body, according to a press release from the university. They analyzed samples of the bacteria collected from patients who were admitted to the hospital over a 10-year period, focusing on older individuals with pre-existing conditions. They found that K. pneumoniae persisted for up to 4.5 years (1,704 days) and E. coli persisted for up to nine years (3,376 days).
“These patients not only repeatedly become ill themselves, but they also act as a source of infection for other people—a reservoir for these pathogens,” said Lisandra Aguilar-Bultet, PhD, the study’s lead author, in the press release.
“This is crucial information for choosing a treatment,” explained Sarah Tschudin Sutter, MD, Head of the Division of Infectious Diseases and Hospital Epidemiology, and of the Division of Hospital Epidemiology, who specializes in hospital-acquired infections and drug-resistant pathogens. Sutter led the Basel University study.
“The issue is that when patients have infections with these drug-resistant bacteria, they can still carry that organism in or on their bodies even after treatment,” said epidemiologist Maroya Spalding Walters, MD (above), who leads the Antimicrobial Resistance Team in the Division of Healthcare Quality Promotion at the federal Centers for Disease Control and Prevention (CDC). “They don’t show any signs or symptoms of illness, but they can get infections again, and they can also transmit the bacteria to other people.” Clinical laboratories working with microbiologists on antibiotic resistance will want to follow the research conducted into these deadly pathogens. (Photo copyright: Centers for Disease Control and Prevention.)
COVID-19 Pandemic Increased Antibiotic Resistance
The Basel researchers looked at 76 K. pneumoniae isolates recovered from 19 patients and 284 E. coli isolates taken from 61 patients, all between 2008 and 2018. The study was limited to patients in which the bacterial strains were detected from at least two consecutive screenings on admission to the hospital.
“DNA analysis indicates that the bacteria initially adapt quite quickly to the conditions in the colonized parts of the body, but undergo few genetic changes thereafter,” the Basel University press release states.
The researchers also discovered that some of the samples, including those from different species, had identical mechanisms of drug resistance, suggesting that the bacteria transmitted mobile genetic elements such as plasmids to each other.
One limitation of the study, the authors acknowledged, was that they could not assess the patients’ exposure to antibiotics.
Meanwhile, recent data from the World Health Organization (WHO) suggests that the COVID-19 pandemic might have exacerbated the challenges of antibiotic resistance. Even though COVID-19 is a viral infection, WHO scientists found that high percentages of patients hospitalized with the disease between 2020 and 2023 received antibiotics.
“While only 8% of hospitalized patients with COVID-19 had bacterial co-infections requiring antibiotics, three out of four or some 75% of patients have been treated with antibiotics ‘just in case’ they help,” the WHO stated in a press release.
WHO uses an antibiotic categorization system known as AWaRe (Access, Watch, Reserve) to classify antibiotics based on risk of resistance. The most frequently prescribed antibiotics were in the “Watch” group, indicating that they are “more prone to be a target of antibiotic resistance and thus prioritized as targets of stewardship programs and monitoring.”
“When a patient requires antibiotics, the benefits often outweigh the risks associated with side effects or antibiotic resistance,” said Silvia Bertagnolio, MD, Unit Head in the Antimicrobial resistance (AMR) Division at the WHO in the press release. “However, when they are unnecessary, they offer no benefit while posing risks, and their use contributes to the emergence and spread of antimicrobial resistance.”
Citing research from the National Institutes of Health (NIH), NPR reported that in the US, hospital-acquired antibiotic-resistant infections increased 32% during the pandemic compared with data from just before the outbreak.
“While that number has dropped, it still hasn’t returned to pre-pandemic levels,” NPR noted.
The UPenn researchers have already developed an antimicrobial treatment derived from guava plants that has proved effective in mice, Vox reported. They’ve also trained an AI model to scan the proteomes of extinct organisms.
“The AI identified peptides from the woolly mammoth and the ancient sea cow, among other ancient animals, as promising candidates,” Vox noted. These, too, showed antimicrobial properties in tests on mice.
These findings can be used by clinical laboratories and microbiologists in their work with hospital infection control teams to better identify patients with antibiotic resistant strains of bacteria who, after discharge, may show up at the hospital months or years later.
Understanding how superspreading occurs can help clinical lab leaders slow and even prevent the spread of SARS-CoV-2 within their communities and health systems
Clinical laboratories understand the critical importance of preventing the spread of infection. However, according to the Boston Globe, researchers worldwide are learning that roughly 80% of new COVID-19 cases are caused by just 10% of infected people. Those people are called superspreaders.
It’s critical that medical laboratory managers are aware of the role superspreaders play in transmitting SARS-CoV-2, the coronavirus that causes the COVID-19 illness.
Clinical lab leaders who understand how superspreading occurs can take steps to protect staff, patients, and anyone who visits the facility. Because lab personnel such as couriers and phlebotomists, among others, come into contact with large numbers of people daily, understanding how to identify superspreaders could limit transmissions of the coronavirus within the laboratory, as well as within hospital networks.
Superspreading versus Plodding
Influenza and other viruses tend to spread in a way that epidemiologists call “plodding.” One person infects another, and the virus slowly spreads throughout the population. However, scientists around the globe are finding that SARS-CoV-2 transmission does not fit that pattern. Instead, a few infected people appear to be transmitting the virus to dozens of other people in superspreading events, Boston Globe reported.
“You can think about throwing a match at kindling. You throw one match, it might not light the kindling. You throw another match, it may not light the kindling. But then one match hits the right spot and all of a sudden the fire goes up,” Ben Althouse, PhD, principal scientist and co-chair of epidemiology at the Institute for Disease Modeling in Bellevue, Wash., told the Boston Globe.
But because roughly 90% of infected people aren’t spreading the virus, identifying who the superspreaders are can be a challenge. Nevertheless, limiting situations in which superspreading is likely to occur could greatly reduce the spread of infection.
Samuel Scarpino, PhD (above), Assistant Professor in the Network Science Institute at Northeastern University, says that “preventing superspreader events could go a long way toward stopping COVID-19,” Scientific American reported. “All of the data I’m seeing so far suggest that if you tamp down the superspreader events, the growth rate of the infections stops very, very quickly,” Scarpino said. (Photo copyright: University of Vermont.)
Examples of Superspreading Events
One of the first big outbreaks in the United States was an example of a superspreading event. The Biogen (NASDAQ:BIIB) leadership conference in late February in Boston resulted in at least 99 cases of COVID-19 just in Massachusetts, reported the Boston Globe.
Several superspreading events have occurred in houses of worship. One well-documented example prompted a CDC Morbidity and Mortality Weekly Report, titled, “High SARS-CoV-2 Attack Rate Following Exposure at a Choir Practice—Skagit County, Washington.” The 122-member choir met for practice twice in March. On March 3 no one had symptoms, but one person had cold-like symptoms at the March 10 practice. Eventually, 53 members tested positive for SARS-CoV-2.
On May 30, a Texas family held a birthday party, Medical Xpress reported. Twenty-five people attended the party, which only lasted a few hours. The family followed the state’s guidelines for gatherings, however one of the hosts was infected with the SARS-CoV-2 coronavirus and wasn’t aware of it. Seven attendees contracted it, and those seven spread the virus to an additional 10 family members. A total of 18 members of a single family were infected.
There are commonalities among the documented superspreading events. Most occur indoors, often in poorly ventilated areas. Some activities cause more respiratory droplets to be expelled than others, such as singing. Some respiratory droplets are released simply by breathing, and many more are expelled when a person talks. Talking louder expels even more droplets into the air.
Are Some People More Likely to Spread the Coronavirus than Others?
The fact that so few people are responsible for the majority of transmissions of the virus raises questions. Do some people simply have more virus particles to shed? Is biology a factor?
One factor may be how long the SARS-CoV-2 coronavirus is in the body before symptoms of the COVID-19 illness manifest.
“If people got sick right away after they were infected, they might stay at home in bed, giving them few opportunities to transmit the virus,” noted Scientific American in “How ‘Superspreading’ Events Drive Most COVID-19 Spread.” However, CDC states on its website that “The incubation period for COVID-19 is thought to extend to 14 days, with a median time of 4-5 days from exposure to symptoms onset. One study reported that 97.5% of persons with COVID-19 who develop symptoms will do so within 11.5 days of SARS-CoV-2 infection.”
During that time, infected individuals may transmit the virus to dozens of other people. The CDC estimates that about 40% of transmission occurs in pre-symptomatic people, Scientific American reported.
But it’s not all bad news. The fact that circumstances may be more important than biology might be good news for clinical laboratories. “Knowing that COVID-19 is a superspreading pandemic could be a good thing. It bodes well for control,” Nelson told the Boston Globe.
Clinical laboratory managers are encouraged to follow CDC recommended safety protocols, titled, “Guidance for General Laboratory Safety Practices during the COVID-19 Pandemic.” They include social distancing, setting up one-way paths through lab areas, sanitizing shared surfaces such as counters and benchtops, and implementing flexible leave policies so that sick employees can stay home.
Following these guidelines, and being aware of superspreaders, can help medical laboratories and anatomic pathology groups keep staff and customers free of infection.
