Charna Albert
July 2024—With the Food and Drug Administration approval in May of two HPV self-collection devices for use in clinic settings, physicians in and out of the laboratory are optimistic the approach can reach underscreened patients, even if FDA approval is only a first step.
A trial that is enrolling this summer will evaluate self-collection device and HPV assay combinations for home collection, and clinical management recommendations are due out later this year.
“It’s a game changer,” Leeya Pinder, MD, MPH, gynecologic oncologist, University of Cincinnati Cancer Center, and clinical associate professor, University of Cincinnati College of Medicine, says of HPV self-collection. “It’s another tool in our tool belt. It’s not the be-all, end-all, but we can now expand screening.”
“It allows us to have a new touchpoint,” she says.
The two approved self-collection devices are from Roche and BD. Patients collect their own vaginal samples in a health care setting, which are then sent to a laboratory for analysis. Those who receive a positive result will continue their care with a provider. Currently, the self-collect devices are not approved for use at home as mail-in tests.
BD’s product is available now, and Roche expects to bring its device to market by the end of summer. BD said in its announcement of the news that the approval permits women to take self-collect specimens in nontraditional locations, such as retail pharmacies or mobile clinics.
The FDA’s approval for the health care setting is likely a transitional step before home collection is approved, says Alicia Carter, MD, vice president and director of anatomic pathology at Labcorp. “I’m still excited about it because sometimes you have to take baby steps and this is the first step to self-collection,” Dr. Carter says. “I think they [the FDA] took this approach most likely because of clinicians’ comments and feedback about worrying about patients not being in the clinic.” Once it’s proved to be an effective method, “that will open the doors for getting this closer to patients in their homes.”
Dr. Pinder is a local principal investigator of the Self-Collection for HPV Testing to Improve Cervical Cancer Prevention (SHIP) trial, a nationwide, multicenter trial that will evaluate device usability and acceptability, accuracy of self-collection device and HPV assay combinations in health care and simulated home settings, and effectiveness in underserved populations. “The major goal is to provide additional post-approval evidence to support its continued use,” Dr. Pinder says. The trial, run by the National Cancer Institute as part of its Cervical Cancer Last Mile Initiative, is enrolling participants this summer. Roche and BD will provide the self-collection kits.
The University of Cincinnati Cancer Center is one of 25 SHIP trial sites. In phase one of the trial, “we’ll be enrolling people who are known to be high-risk HPV positive, and we’ll have them self-collect and then we’ll have a provider collect to provide more evidence that this is accurate,” Dr. Pinder says. In phase two, “we’ll look at expanding self-testing into other avenues, looking at the home setting—if we do mail-in kits, we want to know how our clients or patients respond to it, if it’s adequate sampling, whether we’re able after a positive result to link them to care.” The trial will inform the FDA’s ongoing approval and address generalizability. “A lot of studies are centered and focused on one population,” she says. “Being part of a network gives you multiple different regions and populations.”
Dr. Pinder intends to bring self-collect options to the University of Cincinnati. One possibility is the Early Intervention Program that already exists in the emergency department to test for sexually transmitted infections and is well known in the community. How it would work: “If they’re identified in the [HPV] screening population range and we look at their records and see they haven’t been screened or they’re overdue for screening, we would offer them education and HPV self-testing while they’re in the emergency department. Once we get results it’s a matter of utilizing our community partners and navigators to get them linked to care.” When mail-in testing becomes available, that would be an alternative offered to the same patient population.
“It’s about using a platform that’s already working and leveraging that platform to reach a population that clearly we’re missing.”
Karissa Culbreath, PhD, D(ABMM), medical director and section chief of infectious disease at TriCore and clinical associate professor, University of New Mexico, also sees STI testing as a potential access point for HPV screening. TriCore offers self-collect testing for chlamydia, gonorrhea, and vaginitis, “and in some cases you can use the same swab for multiple types of testing,” she says. Though HPV is more a standard screening than an acute test and wouldn’t typically be offered in that setting, “there may be patients who have missed their HPV, so why not use that same swab?” It’s an opportunity to close care gaps, she says, “and it’s an opportunity to catch them when available. If there’s an FDA-cleared swab, the provider could potentially do an add-on test and identify more patients at risk for HPV and cervical cancer.”
The member organizations of the Enduring Consensus Cervical Cancer Screening and Management Guidelines effort later this year will release clinical management recommendations for the HPV self-collection devices, says Rebecca Perkins, MD, MSc, professor of obstetrics and gynecology at Boston University Chobanian and Avedisian School of Medicine, an obstetrician-gynecologist at Boston Medical Center, and a coauthor of the forthcoming publication.
The recommendations will cover screening, when patients who have a normal result should get retested, and what follow-up testing is needed after an HPV-positive result on a self-collected vaginal sample.
A patient with a self-collected HPV test that’s positive for high-risk HPV16 or 18 can go straight to colposcopy, she says. “But if it’s positive for one of the other types, for the most part they would need to come in, get a speculum exam to collect the cervical cells, those would then be sent for dual stain or cytology,” and depending on the result the patient might need colposcopy. “For the majority of people who test HPV positive, it [self-collect] adds a second step,” she says. Clinician collection, then, would be better for patients who might be anxious about a positive diagnosis and the wait for follow-up testing. In Australia, she says, “they started out using it [self-collection] as an expansion tool and now they are offering it to everybody.” In the U.S., “that may be where it goes eventually, but that’s not where it’s going in summer or fall of 2024.”
The speculum exam will still play a major role, she says. “We can only prevent cervical cancer if we visualize and test the cervix and treat it if it’s abnormal.”
Labcorp’s Dr. Carter says the FDA’s approval comes as a relief for the laboratory. “It negates the pursuit of a laboratory-developed test and all the validations that go along with that.”
But there’s work still to be done on the laboratory side. For one, self-collection could mean a different test code, Dr. Carter says. There is also the IT infrastructure and equipment to think about. “Not all laboratories offer all services for all testing modalities,” she says. With only two platforms approved by the FDA for self-collection, “that could mean a change of equipment for a laboratory.”
Workflow and workforce, too, enter the picture. “Now you have switched from cytology in cotesting as being primary with reflexing to HPV, and there are workflow operational steps to take into account when you reflex to cytology,” she says. And with cytology no longer primary, the staff dedicated to that work become a consideration. “You have to think about all those resources and what to do with those people,” Dr. Carter says. Predicting the demand for primary HPV testing is also difficult. Will the demand bring changes to the laboratory, or will laboratories make investments not knowing what the uptake for HPV primary screening will be?
Dr. Perkins expands on the issue of workflow. A primary HPV sample, unlike a self-collected vaginal sample, is taken from the cervix. The lab can run a cytology or dual stain test off that same sample, so the sample must be kept and processed for triage testing if the result is positive. “But with self-collection you only have vaginal cells, and you can’t process them like they are cervical cells,” she says. “A vaginal self-collection is also primary HPV but is a totally different workflow and is managed differently, in terms of the patient having to come back versus not come back.” The laboratory, then, needs a system to differentiate physician-collected primary HPV specimens from vaginal self-collected specimens. “Because it’s either going to go into process A, where they run the HPV and off that same sample they can run the cytology or dual stain, or it goes into process B, where they can only run the HPV,” Dr. Perkins says.
There’s likely to be confusion around this, she says. “We did a survey of clinicians and asked them what they thought about primary HPV, and I would say most of them thought it was self-collection.”
Thomas Lorey, MD, senior consultant and former director of laboratory services for Kaiser Permanente Northern California, says the obstacles confronting the transition to HPV primary screening can be daunting. Foremost among them, he says: “Discontinuing the venerated Pap smear, a test that has become virtually synonymous with preventive health care.” Despite its unprecedented effectiveness during the past 75 years, “we now have a better test.”
“If we were to start cervical cancer screening today,” he says, “we’d never select a screening test with a sensitivity of 50 percent if there was an alternative with greater than 90 percent. It’s time we allow the Pap test to enjoy a well-deserved retirement.”
To adopt self-collect and eventually home collection, “we must first move to HPV primary.” Self-collection is easy and accessible and enables home testing, Dr. Lorey says. Moreover, the stability of DNA allows a sample to be transported through the mail to the laboratory. “Once home collection is FDA approved, there is the potential to significantly decrease the number of office visits and pelvic exams. Assuming a 10 percent HPV positivity rate, home collection could potentially eliminate 90 percent of pelvic exams.” In the future, cell-free biomarkers of transformation, such as methylated DNA, which is not FDA approved, could make it possible to triage HPV-positive women directly from a self-collect specimen without having to call them back into the clinic, he says.
Is the self-collect approach as sensitive as physician-collected methods? “That’s a primary concern of all of us,” Dr. Lorey says. “The data we have thus far suggests it can be done in an equivalent fashion. That said, if there is some slight degradation in sensitivity, I don’t think that alone should kill it. The increased sensitivity of HPV testing, combined with the convenience of self-collection, will likely make this a great option for many.”
Kaiser Permanente is in the nascent stages of developing an HPV self-collect pilot. “To decrease risk during the pilot, we’re enrolling only individuals with a history of a previous negative screen, whether Pap, cotest, or HPV. So the risk is already cut in half,” he says. (When a new abnormal screening test result follows a negative HPV test or cotest within the past five years, the estimated risk of cervical precancer is reduced by about 50 percent, according to the 2019 American Society for Colposcopy and Cervical Pathology Risk-Based Management Consensus Guidelines.)
Another potential barrier to a large-scale effort: reimbursement. “Regardless of where the specimen is collected, at home or in the office, there’s a provider responsible for the test result and for patient follow-up, and they need to be compensated,” Dr. Lorey says. The billing systems in the U.S. aren’t set up for large-scale community health outreach efforts, he adds. “It’s going to take some creativity, but we will get there.”
Dr. Pinder says that permitting women to take self-collected specimens in nontraditional locations would help increase access. “In certain populations, routine everyday screening is not working. Making women come in for multiple visits and scheduling at inconvenient times doesn’t work for everyone.”
Says TriCore’s Dr. Culbreath, “What we’ve seen from the pandemic with self-collect options for SARS-CoV-2, what we’ve seen with self-collect options for STIs, is these options go a long way to increase access to diagnostics.”
Labcorp performed the testing for the My Body, My Test-3 trial. That trial assessed the efficacy of mailed HPV self-collection kits in conjunction with appointment scheduling assistance (intervention group) to increase uptake of cervical cancer screening among underscreened women from low-income backgrounds compared with scheduling assistance alone (control group) (Pretsch PK, et al. Lancet Public Health. 2023;8[6]:e411–e421). The primary outcome was cervical cancer screening completion, defined as attending an in-clinic screening appointment or testing negative for high-risk HPV on a returned self-collected sample, within six months of enrollment. Screening uptake was higher in the intervention group (317 of 438 [72 percent]) than the control group (85 of 227 [37 percent]). Among intervention participants, 341 of 438 (78 percent) returned a self-collection kit.
Of those who returned a self-collection kit, 11 participants (three percent) had final invalid self-collected results, and one participant sample was received damaged, leaving a total of 329 participants (96 percent) with valid HPV self-collection results. “The data for HPV self-collection looks promising,” Dr. Carter, a coauthor, says, “and I think we have enough. The fact that it has been FDA cleared now speaks volumes.”
Including educational materials with the kits is important, she says, as is assisting with follow-up. The instructions for follow-up could be integrated with the kit instructions, or a service for follow-up could be offered with the kit.
The challenge of getting patients to return to the clinic for triage testing may give some clinicians pause about self-collection. “Sometimes we look at those limitations and say it’s reason enough not to perform the testing,” Dr. Culbreath says. “For me, that’s not the case, because information is always valuable.” If only one of 10 positive patients completes follow-up, she says, the other nine still have been informed they are positive and have the opportunity to seek further care. “Hopefully they will eventually.”
“We live in this world where we pretend, ‘Well, if we don’t know what the follow-up plan is, let’s just not screen them,’” she says. “But that doesn’t change the fact they’re positive.”
The linkage to care for patients who need follow-up testing is important, Dr. Pinder says. At the University of Cincinnati, “we’re fortunate because we’re part of a system that has community navigators,” which she describes as “our point of education.” Social services often provides transportation. Drop-in clinics with weekend and evening hours are not available now but also would help, she says.
To streamline the multi-visit pathway that’s necessary now for women who have abnormalities, Dr. Pinder is seeking funding for a study that would assess mail-in self-collect testing and the potential to reduce the number of clinic visits to one all-inclusive appointment. “If someone can self-test at home and then we receive their results, if they have a positive test they can come in and get their visualization and treatment on the same day, versus having them come back multiple times.”
Some are concerned that the self-collect option will discourage patients from scheduling annual gynecologic exams. “We in gynecology are sensitive to all the other things that can go on with women,” Dr. Pinder says. “So we are advocates of annual visits so we can address all problems and concerns,” including mental health. “When you take that element out by offering HPV self-testing, historically the thought is people won’t come in for their annual visit because now they’re swabbing themselves,” she says. “I emphasize that it’s a tool in a toolkit, because a lot of these people aren’t coming in anyway.”
Home self-collection, Dr. Carter says, “is a step toward equitable access to care and ensuring the most vulnerable don’t fall through the cracks.”
“Think about the opportunity we have to bring in the 15 percent of the population who should be seeing a doctor—now they’re going to get a test that could potentially bring them into a clinician’s office. That’s where we need to focus our attention,” she says.
Health equity and access has long been a focus in many areas of medicine, Dr. Culbreath says. “Lab medicine and pathology has been a little slower to move in that direction.”
“We’ve believed that since we’re not always the ones seeing patients or collecting the specimen, that we’re a step removed from the equity at work—we’re a step removed from the access. The providers are the ones who have access, and we test the specimens.”
The pandemic accelerated Dr. Culbreath’s shift toward equity work. “We were supporting out in the community and helping with specimen collection and doing work to increase access to diagnostic testing. If we take all those lessons,” she says, “there are ways as laboratorians we can increase access to diagnostics.”
That’s what Guang Fan, MD, PhD, did. She is chair and professor of pathology and laboratory medicine at Oregon Health and Science University School of Medicine and medical director of the clinical laboratory. Dr. Fan assisted with OHSU’s mobile SARS-CoV-2 testing outreach program in the winter of 2021. Since then, she has teamed up with OHSU’s Center for Women’s Health to provide on Saturdays free cervical and breast cancer screening at Multnomah County clinics. She hopes to bring an HPV self-collection option to OHSU’s mobile van outreach program by the end of this year. They will work with OHSU’s health equity team and inform state officials of the now approved self-collection devices. “The state may be able to fund us,” Dr. Fan says.
OHSU providers are eager to make use of self-collection in the underserved population. Though the clinical workflow details are unknown at this point, “they feel like the workflow will be easier,” she says.
Home collect will happen whether or not the laboratory is involved, Dr. Culbreath says. “If we don’t insert ourselves into the process, home collect will happen without us, and we’ll receive a swab and won’t know where it came from. I want to be part of the work to make sure the highest quality laboratory testing is happening, whether it’s on a mobile unit, at the point of care, or in any other type of setting, and that we’re getting diagnostics out to the communities that need them.”
Dr. Pinder would agree. “The platform by which we normally screen people, or have historically screened people,” she says, “just isn’t working.”
Charna Albert is CAP TODAY associate contributing editor.