MedicalResearch.com Interview with:
Megan Clarke, PhD, MHS
Cancer Prevention Fellow
Clinical Genetics Branch
Division of Cancer Epidemiology & Genetics
National Cancer Institute
Rockville, MD 20892
MedicalResearch.com: What is the background for this study?
- Infection with high-risk human papillomavirus (hrHPV) is the primary cause of cervical cancer. While hrHPV infection is common, most infections are benign and clear on their own without causing cervical cancer. However, some women develop persistent hrHPV infections and are at risk for cervical cancer and its precursors (i.e., precancer).
- The United States Preventative Services Task Force recommends screening every 3 years with cervical cytology (i.e. Pap) alone, every 5 years with hrHPV testing alone, or with a combination of hrHPV testing and cytology (co-testing) for women aged 30 to 65 years.
- Screening with hrHPV testing is highly sensitive for detecting cervical precancer but requires additional triage tests to identify HPV-positive women at high-risk of developing cancer who should undergo colposcopy (visualization of the cervix) and biopsy from those at low-risk who can be safely monitored.
- Currently, Pap cytology is recommended as a triage test for women testing HPV-positive, but this approach requires frequent re-testing at short intervals because the risk of cervical precancer is not low enough in HPV-positive women who test cytology negative to provide long-term reassurance against future risk. In most settings, women who test HPV-positive, cytology-negative are referred to repeat screening within one year.
- The p16/Ki-67 dual stain assay is a molecular test that measures two specific proteins, p16 that is strongly linked with hrHPV infection, and Ki-67, a marker of cell proliferation that is common in precancers and cancers.
- Studies have shown that the dual stain test has greater accuracy for detecting cervical precancers in HPV-positive women compared with cytology.
- In order to determine the optimal screening intervals for the dual stain test, long-term prospective studies are needed to determine how long HPV-positive women who test dual stain negative can be safely reassured of a low precancer risk.
MedicalResearch.com: What are the main findings?
- We conducted the first study evaluating the long-term performance of dual stain in 1,549 HPV-positive women undergoing routine screening with co-testing at Kaiser Permanente Northern California over a 5-year period.
- Overall, 46% of women in the study had a positive dual stain test, compared to a 51% Pap-test positivity. Women with a positive dual stain test had a higher risk of developing cervical precancer over the 5-year period compared to women with a positive Pap test result, suggesting that using the dual stain test to triage HPV-positive women would lead to lower referral rates (to colposcopy and biopsy), but greater disease detection compared with Pap cytology.
- Importantly, women with a negative dual-stain test result had a lower risk of developing cervical precancer within 5 years, compared to women with a negative Pap test. This risk was very low within the first 3 years, suggesting that women with a negative dual stain result can wait 3 years before being screened again.
MedicalResearch.com: What should readers take away from your report?
- Dual stain is more accurate and efficient for detecting cervical precancers compared with Pap cytology for triage of HPV-positive women.
- The low risk of cervical precancer in HPV-positive women who test dual stain negative permits safe extension of follow-up screening intervals for 3 years.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Future studies should evaluate the performance of the dual stain test in other healthcare settings and in different populations, such as women who received the HPV vaccine.
Dual stain is more accurate and efficient for detecting cervical precancers compared with Pap cytology for triage of HPV-positive women.
Clarke MA, Cheung LC, Castle PE, et al. Five-Year Risk of Cervical Precancer Following p16/Ki-67 Dual-Stain Triage of HPV-Positive Women. JAMA Oncol. Published online October 11, 2018. doi:10.1001/jamaoncol.2018.4270
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