HPV Genotyping and Reflex Cytology Efficient for Cervical-Cancer Screening

By Will Boggs MD

December 03, 2019

NEW YORK (Reuters Health) - Human papillomavirus (HPV) genotyping for HPV-16 and HPV-18, followed by reflex cytological testing in women with positive results, is more likely than cytological testing alone to detect cervical intraepithelial neoplasia (CIN) grade 2 or higher, according to results from the FRIDA study.

HPV testing has higher throughput, greater sensitivity and better reproducibility than standard cytological examination, but the best combination of triage tests for cervical screening using primary HPV testing remains unclear.

Dr. Jorge Salmeron of the National Autonomous University of Mexico, in Mexico City, and colleagues compared the clinical test performance of the current triage tests available in Mexico (liquid-based cytology, or LBC, testing and HPV-16 or HPV-18 genotyping, individually or in combination) as sequential tests to detect CIN grade 2 or higher among women with high-risk HPV participating in a routine-cervical-cancer-screening program.

They compared six triage scenarios for referring to colposcopy: 1) an LBC finding of atypical squamous cells of undetermined significance (ASCUS) or worse; 2) positive results of HPV-16 genotyping; 3) positive results of HPV-18 genotyping; 4) positive results of HPV-16/HPV-18 genotyping; 5) positive results of HPV-16 genotyping or, if genotyping results were negative, reflex LBC finding of ASCUS or worse; and 6) positive results of HPV-18 genotyping or, if genotyping results were negative, reflects LBC finding of ASCUS or worse.

The adjusted sensitivity for detecting CIN grade 2 or higher was twice as high for HPV-16/HPV-18 genotyping with reflex LBC (53.8%) than for LBCA alone (26.7%), although LBC had higher adjusted specificity (89.7% vs. 74.1%), the team reports in JAMA Network Open, online November 20.

Test characteristics were similar for detecting CIN grade 3 or higher.

The sequential triage tests were associated with the highest proportion of colposcopy referrals, but also with the highest detection rate of CIN grade 2 or higher. The strategy of HPV-16/HPV-18 genotyping and reflex LBC required 7.2 colposcopies to detect 1 CIN grade 2 or higher, compared with 5.9 colposcopies required by LBC alone.

"This diagnostic study found that HPV-16/HPV-18 genotyping with reflex LBC for triaging women with high-risk HPV is an appropriate method to achieve the goal of preventing cervical cancer in settings where access to appropriate follow-up is challenging, assuming that the costs and burden of overtreatment are offset by the individual and social benefits of preventing cervical cancer," the researchers conclude. "Perceptions and preferences of women and health care professionals, as well as the resources required, are key factors that should be addressed to ensure effective screening programs."

Dr. Rachel Kupets of the University of Toronto and Sunnybrook Health Sciences Centre, in Toronto, Canada, who studies cervical-cancer screening, told Reuters Health by email, "Organized screening programs must determine the best guidelines for their population for cervical-cancer screening and prevention to identify effectively the most women with cervical precancer on their cervix so they can be treated and cervical cancer is then prevented."

"Testing women for the absence or presence of the viruses that actually cause cervical cancer allows us to focus more on risk-based strategies and focus more accurately on women who are truly at risk for cervical cancer while reassuring those women who do not have high-risk HPV infections," she said.

"Programs must also minimize harms," said Dr. Kupets, who was not involved in the new research. "Colposcopy, which is the next step for women with abnormal cervical screen tests, may be associated with pain, infections, anxiety, and unneeded treatments, which can lead to bleeding, cervical stenosis, or inability to carry pregnancy to term."

"Participation is key to eradicating cervical cancer," she said. "Of women who develop cervical cancer, more than 50% have not been screened in 5 years or more."

Dr. Kupets added, "HPV vaccination of young girls (and boys) should be encouraged in school-based programs. Cervical cancer can be eradicated by high vaccination rates and screening rates (Australia predicts they will convert cervical cancer to a rare tumor (<4/100,000) in the next 10-15 years (and) it may actually be sooner)."

Roche Molecular Systems, Becton Dickinson, DICIPA, and Arbor Vita Corporation supported the study and had various relationships with several of the authors.

Dr. Salmeron did not respond to a request for comments.

SOURCE: https://bit.ly/35DNsED JAMA Netw Open 2019

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