New and Updated Guidelines for Cervical Cancer Screening

Question: I’m a provider and am aware that there have been new developments in cervical cancer screening technologies. How do the updated guidelines take these developments into account, and how do they affect my practice?

Dr. Michael Policar responds: Since the publication of the updated chapter on Screening for Cervical, Ovarian, and Breast Cancer in Contraceptive Technology (22nd edition),¹ there have been four new developments in cervical cancer screening, moving us closer to personalized management: primary HPV screening for average risk patients, self-sampling for some people, dual staining of cytology samples, and extended HPV genotyping. Clinicians need to be aware of the updates in national guidelines, and in some cases, utilize these new technologies, depending on the logistics of cervical cancer screening in your practice.

In December 2024, the US Preventive Services Task Force (USPSTF) published a draft of their Recommendation Statement on Cervical Cancer: Screening². The statement has two important new components for screening persons 30 to 65 years of age:
- Primary HPV screening (with a high-risk HPV test-alone) every 5 years as the preferred screening strategy in this age group
- Obtaining a clinician- or a patient-collected high-risk human papillomavirus (HPV) sample.
The ASCCP published three new guidelines in the Journal of Lower Genital Tract Disease based on recommendations written by the Enduring Consensus Cervical Cancer Screening and Management Guidelines Committee: (1) self-collected vaginal specimens for HPV testing³ (April, 2025) (2) recommendations for the use of p16/Ki67 Dual Stain⁴ (April, 2024), and (3) applying results of extended genotyping to management of positive cervicovaginal HPV test results⁵(April, 2025).

Primary HPV Screening

Earlier versions of the USPSTF guidelines (most recently in 2016), recommended 3 co-equal options in screening for cervical cancer in women 30-65 years of age: cytology every 3 years, co-testing (cytology and an HPV test ) every 5 years, and HPV-alone (primary screening) every 5 years. In the 2024 USPSTF draft, HPV-alone screening is given top billing, based upon comparison of the benefits (preventing cervical cancer cases and deaths) and the harms (false positives leading to unnecessary colposcopy and treatment) of each approach. Meta-analyses showed that while all three approaches led to similar profound reductions in cervical cancer cases and deaths, primary HPV screening resulted in fewer tests performed and fewer colposcopies, but slightly more cancers per 1,000 women over a lifetime when compared to co-testing. However, given similar benefits, the guideline stated that as an alternative to primary HPV screening, continued screening with cervical cytology alone every 3 years or screening with co-testing every 5 years is acceptable. Note that these guidelines apply only to average-risk patients, which is defined as not having a medical condition that causes immunocompromise, no history of in-utero DES exposure, and no history of CIN 2+ in the past 25 years.

Every clinician who performs cervical cancer screening should be familiar with the ASCCP Management Guidelines app, which can be purchased for $14.99. The same information is available for free from the ASCCP website at https://www.asccp.org/mobile-app. The management guidelines contained in the app have been updated to provide advice to clinicians regarding the management of clients with a positive HPV test and the reflex cytology that is performed in the same lab

Self-sampling³

Self-sampling for HPV in order to screen for cervical cancer precursors has been a topic of interest for decades, as this approach is likely to improve screening rates in people who prefer to avoid a clinician-performed speculum exam and for those unable or unwilling to be evaluated in a clinical setting. Precedent exists for successful self-sampling for other lower genital tract pathogens (e.g., obtaining gonorrhea and chlamydia specimens for nucleic acid amplification tests).

Studies in Europe and the US have shown that self-collected HPV tests are slightly less sensitive than clinician-collected tests (relative sensitivity, 0.91-0.94). Consequently, the Enduring Consensus Guideline2 stated that while clinician-collected cervical specimens are preferred, self-collected vaginal specimens are acceptable for primary HPV screening of asymptomatic average-risk individuals as defined above. Given the drop-off in sensitivity, repeat testing in 3 years, rather than the usual 5 years, is recommended following HPV-negative screens using self-collected vaginal specimens. Minimal data regarding surveillance following abnormal screening test results, colposcopy, or treatment are available, and therefore, clinician-collected cervical specimens are preferred in these circumstances.

This recommendation applies only to tests with an FDA indication for primary HPV screening using self-collected vaginal specimens. These include the BD Onclarity HPV Assay with the Copan 522C.80 swab and the Roche cobas assay with Evalyn brush or Copan 522C.80 swab. If not supplied by the pathology lab that your practice uses, the Copan swabs can be purchased for about $1 each and the Evelyn swab costs about $6 each. Meta-analyses show a high level of acceptability and preference for self-collection over clinician sampling (ease and privacy)⁶ and increased screening rates compared with an invitation to clinic (12% absolute increase)⁷ ,

At this time, self-collection devices are FDA-approved only for use in medical settings, including clinics, offices, mobile vans, urgent care centers, etc., but not for home collection because there are not yet adequate studies to validate home collection. However, one study done in North Carolina using home self-collection shows that this approach is acceptable for clients and may make home sampling more cost-effective than clinic-based collection for detection of CIN2+⁸

Important caveats regarding HPV self-collection

If you plan to start the self-collection option in your clinic or office, check to make sure that your path lab is using either the BD Onclarity or the cobas test and that the appropriate collection swabs are used.
Self-collection applies only to the 30-65 age group, as persons 21-29 are still screened with cytology alone every 3 years.
The published guidelines do not apply to self-sampling at home or non-clinical settings…yet. However, outside of the guidelines, a number of companies offer home HPV collection kits that can be purchased online, including the costs of transferring the sample to a lab, the performance of the HPV test, and providing the client with the test results. Most of these products require the client to pay out-of-pocket and they are not covered by Medicaid, state family planning programs, or commercial health insurance at this time.

Dual Staining⁴

In 2020, the US FDA approved the use of p16^ink4a/Ki-67 dual stain (DS) for cytology samples to inform the management of those with a positive HPV test. These stains check for activity of p16, (a tumor suppressor protein which reflects HPV-related oncogene activity) and Ki-67 which is a marker of cell proliferation. Detection together in the same cell is strongly associated with precancerous cellular changes (CIN3+). Not all pathology laboratories perform this test…check to determine whether it is available to your clients in the lab that you use, whether the test is done at the discretion of the pathologist or if it has to be ordered separately, and whether it is a benefit of the client’s health plan or payer.

In general, HPV+/DS+ will prompt colposcopy; HPV+/DS- will prompt return in one year. Note that dual staining results are included in the ASCCP app so that you won’t have to look up management recommendations when this test has been performed in the lab

However, if you don’t have the app available or need more detailed management information, the table below is excerpted from the Enduring Guidelines⁵ article by Massad in the Journal of Lower Genital Tract Disease.

Table 7. Summary of Management With Extended HPV Genotyping and p16^ink4a/Ki-67 Dual Stain (DS) for Patients Undergoing Screening and Follow-Up of Low-Grade Abnormalities.
	Current HPV	Current DS result	Past history	Management
HPV 16/18	16 and/or 18	N/A¹	N/A	Colposcopy with collection of cytology if available
HPV 45, 33/58, 31, 52/35/39/68, 51 Untyped or “other” types when 16 or 18 are not present	45, 33/58, 31, 52/35/39/68, 51 or untyped/other	DS Positive²	N/A	Colposcopy
	45, 33/58, 31, 52/35/39/68, 51 or untyped/other	DS Negative³	Normal⁴ or colposcopy <CIN2⁵ within past 1 year	Repeat HPV test in 1 year
	45, 33/58, 31, 52/35/39/68, 51 or untyped/other	N/A	HPV+ without colposcopy (i.e. current test is 2nd consecutive HPV+)	Colposcopy
HPV 59/56/66	59/56/66	N/A	Normal or colposcopy <CIN2 within past 1 year	Repeat HPV test in 1 year²
	59/56/66	N/A	HPV+ without colposcopy (i.e. current test is 2nd consecutive HPV+)	Colposcopy

Extended genotyping⁵

Currently, six different high risk HPV screening tests are commercially available in the US: Hybrid Capture 2, Cervista, Aptima (E6/E7), cobas, BD Onclarity, and Alinity . Only cobas, BD Onclarity and Alinity are FDA cleared for primary screening, while the others are approved for co-testing and triage of ASC-US cytology results. Each one tests for 13 or 14 high-risk HPV types; some also test for specific high-risk types (16, 18, 18/45). Some laboratories have developed their own “in-house” (or “home-grown”) HPV genotyping tests that have not been reviewed by the FDA, making it difficult to comment on their accuracy.

We now know that the “12 other” high-risk HPV types, when present or absent, have the potential to further stratify patients into risk categories. Two FDA-cleared assays provide extended genotyping of specific HPV types: the Onclarity HPV Assay (approved April 2020) and the Alinity m High-Risk HPV Assay (approved November 2023). Extended HPV genotyping results are interpreted in the context of current and prior cytology and/or dual stain results. In general, extended HPV genotype test results indicating relatively higher risk HPV strains will lead to colposcopy in some persons with minimally abnormal cytology who would otherwise have had repeat testing in 1 year

Results of extended genotyping (beyond HPV 16, 18, and 45) are not included in the ASCCP app. Detailed management information, based on current HPV type (from extended HPV genotyping) and current and past cytology results, are included in the table below, which is excerpted from the Massad Enduring Guidelines⁵article.

Table 6. Summary of Management With Extended Genotyping When Used With Cotesting or Cytology Triage of Primary HPV Testing for Patients Undergoing Screening and Follow-Up of Low-Grade Abnormalities.
	Current HPV	Current cytology	Past results	Management
HPV 16/18	16	HSIL¹	N/A²	Treatment preferred; colposcopy acceptable
	16	ASC-H³	N/A	Treatment or colposcopy
	16	NILM⁴, ASC-US⁵, LSIL⁶, AGC⁷, or no cytology	N/A	Colposcopy⁸ with collection of cytology if not already done
	18	HSIL	N/A	Treatment or colposcopy
	18	NILM, ASCUS, LSIL, ASC-H, AGC, or no cytology	N/A	Colposcopy⁸ with collection of cytology if not already done
HPV 45, 33/58, 31, 52/35/39/68, 51 Untyped or “other” types when 16 or 18 are not present	45, 33/58, 31, 52/35/39/68, 51 or untyped/other	HSIL, ASC-H, AGC	N/A	Colposcopy^8,9
	445, 33/58, 31, 52/35/39/68, 51	ASC-US or LSIL	N/A	Colposcopy
	Untyped/other	ASC-US or LSIL	Documented HPV negative screen in past 5 years or colposcopy <CIN2¹⁰ in past year	Repeat HPV test in 1 year
	Untyped/other	ASC-US or LSIL	Any history other than above	Colposcopy
	45, 33/58, 31, 52/35/39/68, 51 or untyped/other	NILM	Normal¹¹ or colposcopy	Repeat HPV test in 1 year
	45, 33/58, 31, 52/35/39/68, 51 or untyped/other	N/A	HPV+ without colposcopy (i.e. current test is 2nd consecutive HPV+)	Colposcopy
HPV 59/56/66	59/56/66	ASC-H, AGC, or HSIL¹²	N/A	Colposcopy⁸
	59/56/66	NILM, ASC-US, LSIL or no cytology¹²	Normal or colposcopy	Repeat HPV test in 1 year
	59/56/66	N/A	HPV+ without colposcopy (i.e. current test is 2nd consecutive HPV+)	Colposcopy

In summary, these advances move us even closer to “personalized management” based on abnormal cervical cancer screening results. However, it’s important to make sure that these interventions are implemented in collaboration between your practice and the pathology lab that your practice works with.

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