CLN - Feature
Draft cervical cancer testing guidelines from the U.S. Preventive Services Task Force (USPSTF) newly endorse women’s collection of their own cervical samples for human papillomavirus (HPV) testing.
For most women ages 30 to 65, the guidelines elevate primary HPV (prHPV) testing every 5 years as the preferred cervical cancer screening method, while also continuing to recommend cytology every 3 years or a combined HPV/cytology (co-testing) every 5 years as alternatives. Cytology every 3 years continues to be the recommended screening method for individuals ages 21 to 29.
Although the guidelines do not specify self-collection location, an evidence report accompanying the draft guidelines notes that the Food and Drug Administration (FDA) has thus far approved expanded indications for self-collection of vaginal swabs in healthcare settings only. BD’s Onclarity HPV Assay and the Roche cobas HPV Assay have the FDA indications.
Self-collected HPV samples would help reduce persistent health disparities, the draft says.
These disparities are driven by personal barriers such as health illiteracy, religious or social preferences, physical disability, or history of trauma, plus society-wide problems such as lack of properly trained providers in rural areas, financial insecurity, and lack of adequate insurance coverage.
The proposed recommendation is a start to fixing disparities because collection could potentially occur in any medical setting, said gynecological oncologist Jennifer Pierce, MD, MPH, division director of cancer control and prevention and professor of interdisciplinary clinical oncology at University of South Alabama. “Self-testing can potentially be offered in nontraditional healthcare settings, such as urgent care settings or FQHCs (federally qualified health centers) when there’s no doctor who is trained to do a good pelvic exam.”
The draft recommendations arrive as decreases in cervical cancer mortality rates have slowed. Most cases occur among inadequately screened groups.
The guidelines call out low screening rates and high incidence and mortality rates in Appalachia, the southeastern Atlantic states, and the lower Mississippi Valley. They note higher rates of disease and mortality in Hispanic women. Black women’s age-adjusted cervical cancer mortality rate is about 1.5 times the rate for white women, despite similar screening rates.
The guidelines also recognize screening disparities among underinsured women and transgender men.
The self-collection recommendation brings the draft USPSTF recommendations closer to common practice in the Netherlands, Denmark, Sweden, Australia, and other developed countries.
Studies show prHPV screening with both self-collected and physician-collected samples is accurate, but the self-collection option increases screening rates, especially among groups with low screening rates, the draft guidelines say.
USPSTF reviewed 14 studies on agreement between self-collected vaginal and clinician-collected HPV samples and six studies on the absolute or relative test accuracy of self-collected vaginal HPV samples to detect CIN2+ or CIN3+ lesions.
Agreement between self-collected vaginal and clinician-collected cervical samples was high, with similar proportions screening positive. Pooled absolute sensitivity of self-collected samples to detect CIN2+ was 0.86. The pooled absolute specificity was 0.81.
Relative accuracy of self-collected vaginal samples to detect CIN2+, compared with the accuracy of clinician-collected samples, was also high. Their relative sensitivity was 0.94 to 0.99 and relative specificity was 0.98 to 1.02.
In 40 of 42 randomized controlled trials (RCT) comparing uptake of self-collected vaginal HPV testing with usual care, offering self-collected vaginal HPV tests increased cervical cancer screening rates.
CLIA requires labs running HPV assays to validate them for self-collection, the draft guidelines note.
USPSTF based elevation of prHPV testing on review of six RCTs and two nonrandomized studies of interventions, including a total of 63,241 women ages 25 to 64 years. Together, these studies showed prHPV screening detects more CIN3+ lesions in one round of screening compared with cytology.
Relative risk (RR) was 1.80. Two RCTs with a combined 67,298 subjects reported decreased detection of CIN3+ after two rounds of screening, with RR of 0.42 and 0.22. An additional trial with 13,925 participants compared self-collected to clinician-collected prHPV screening and found no differences in CIN3+ or CIN2+ detection.
A statement from the American College of Obstetricians and Gynecologists, which declined to discuss the draft, said “HPV vaccination and routine cervical cancer screening are the most important tools we have for prevention and early detection of cervical cancer, and we must ensure that these proven, evidence-based strategies are accessible to all people who need them.” The statement called for improved access to care and meeting individual needs and preferences.
Pierce once preferred cotesting over primary HPV screening. But after the COVID-19 pandemic and ubiquitous home sample collection for SARS-Cov-2 and flu, she approves of prHPV with self-collection.
“HPV is also an infectious disease, and information is empowering,” Pierce said. “No one should withhold an opportunity for patients to have information because of paternalistic concern that people are better off in the doctor's office when some of them are never going to come in.”
The FDA is “very particular about humans collecting their own samples,” said Dina Greene, PhD, clinical professor at University of Washington. “Women or people with cervices are taught to use menstrual products as adolescents, but an adult is considered incapable of swabbing their own vagina for an STI test or for their own cervical cancer screening.”
Greene believes that some labs and physician practices may see a financial incentive to cytology because it drives more billable services.
Meanwhile, prHPV provides HPV-genotype information and “a much more quantitative stratification of cervical cancer risk” than even cytology aided by artificial intelligence, said Vikrant Sahasrabuddhe, MBBS, MPH, DrPH, who co-leads the Self-collection for HPV Testing to Improve Cervical Cancer Prevention (SHIP) trial at the National Cancer Institute.
Many providers want to use prHPV because it informs disease management with a single test. But they are subject to health system directives to use cytology and co-screening, often because of system contracts. These systems could search their EHRs for patients who are under-screened and have any provider offer self-collection and prHPV, Sahasrabuddhe pointed out.
Among “individuals opting for self-collect, only those that test HPV positive (10–30%, depending on HPV positivity rate) will require a pelvic speculum exam to obtain a cervical sample for cytology-based triage testing,” noted Thomas Lorey, MD, senior consultant and former director of laboratory services for Kaiser Permanente Northern California.
PrHPV screening can decrease overall costs by immediately identifying who needs to go directly to colposcopy, based on positive results for HPV 16 and 18, said Nicole Chaisson, MD, MPH, assistant professor of family medicine and community health at University of Minnesota and past chair of the American Academy of Family Physicians (AAFP) Commission on Health of the Public and Science Subcommittee on Clinical Recommendations and Policies.
Traditional cotesting may lead to more use of resources and patient time and result in cytology with atypical, yet not necessarily precancerous findings, particularly if the HPV test is negative. Testing algorithms for this scenario require more frequent assessment, including repeat cotesting and colposcopy as follow-up.
For patients, this scenario involves burdens such as missing work, travel, and monetary costs, Chaisson noted. “Cytology does not necessarily add new data in this case, but may cause confusion and lead to more testing.”
The National Cancer Institute’s SHIP trial aims to add evidence about self-collection that could ultimately lead to women being able to collect samples at home, likely with devices obtained from health professionals, Sahasrabuddhe said. SHIP involves a master protocol as a framework for industry-specific subprotocols.
The FDA required BD and Roche’s participation in SHIP as a condition of their self-collection options’ approvals. The trial, which is now enrolling participants, will initially evaluate each company’s self-collection devices in patients who had prior screening and need colposcopy. A total of 1,500 participants will use three self-collection devices (two from Roche and one from BD) and undergo clinician collection in a single visit. Future subprotocols will follow patients — including underscreened and underserved women — who need cervical cancer screening, Sahasrabuddhe said.
Labs should prepare for prHPV screening as the main default method of cervical cancer screening by making internal flow processes support it, said Diane Harper, MD, MPH, of the University of Michigan Department of Family Medicine, Obstetrics & Gynecology, and Gender Studies, where she leads her institution’s participation in SHIP.
Lorey predicts “some resistance to discontinuing the time-honored Pap test.” He added: “By educating clinicians and patients about the value of prHPV testing, labs can help ease this transition.”
“It requires a lot of education,” Pierce emphasized. “Both patients and doctors must understand that a positive HPV test means the patient needs further follow up.”
Harper offered specific advice for labs on emphasizing to physicians that “prHPV screening is the appropriate default way to screen women and stop promoting cotesting.”
Labs should tell clinicians they offer prHPV screening, offer related educational information, and ask clinicians to consider prHPV for patients, Harper said. Many clinicians want prHPV, but “don't know how to connect with their laboratories to make it happen,” she said. “Having the laboratories proactively promote primary HPV screening … would be helpful so that we’re all sending the same message.”
Deborah Levenson is a freelance writer in College Park, Md. +Email: [email protected]