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Dual stain more sensitive than Pap for triage of HPV-positive women

P16/Ki-67 dual stain testing has higher sensitivity and specificity compared with Pap testing for triage of HPV-positive women, according to results from a recent study published in JAMA Internal Medicine.

“Cervical cancer screening is shifting from primary Papanicolaou cytologic testing to primary HPV testing worldwide,” Nicolas Wentzensen, MD, PhD, MS, of the division of cancer epidemiology and genetics at the National Cancer Institute, and colleagues wrote. “Women with negative results for HPV are reassured of a low risk of cervical cancer for many years and screening intervals can be safely extended compared with primary cytologic screening.”

Researchers conducted the study within the Kaiser Permanente Northern California cervical screening program, which recommended that women who were HPV-negative return for screening after 3 years; women undergo immediate colposcopy if HPV-positive atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesions, or more severe cytologic results; and those who test positive for HPV with negative cytologic results should return for cotesting after 1 year and given a colposcopy when HPV or Pap testing results are positive.

The study evaluated the performance of dual stain and partial genotype testing in all HPV-positive women who were cotested for screening, triage, surveillance and management. In addition, a subset of newly identified HPV-positive women from the 42 months preceding the study who did not have abnormal test results were evaluated.

The primary outcome of the study was a diagnosis of cervical intraepithelial neoplasia grade 3 or more severe (CIN3+) and grade 2 or more severe (CIN2+) within 3 years of sample collection.

From Sept. 16 to Oct. 31, 2015, researchers enrolled 3,225 women with a mean age of 37.7 years in the study. Dual stain showed better risk stratification for CIN3+ than Pap testing, and women with positive dual stain results were at higher risk for CIN3+ than those with positive Pap test results (218 of 1,818 [12%; 95% CI, 10.5-13.5] vs. 219 of 2,128 [10.3%; 95% CI, 9-11.6]). Dual stain also had better risk stratification in HPV-positive women irrespective of genotype. In women who were HPV16/18-negative, negative dual stain results were found to be the greatest reassurance against CIN3+, with results low enough to extend participants’ testing intervals.

Researchers observed a 32.1% decrease in colposcopies among dual stain triage strategies compared with HPV screening with Pap testing, the triage strategy currently in place.

“Dual stain reduces unnecessary colposcopy referral and unnecessary cervical biopsies, and may reduce unnecessary treatment compared with Papanicolaou cytologic testing,” Wentzensen and colleagues wrote. “Our estimates of sensitivity, absolute risk, and colposcopy referral for various triage strategies can guide implementation of primary HPV screening.” – by Erin Michael

Disclosures: Wentzensen is employed by the National Cancer Institute, which has received cervical cancer screening assays in-kind or at reduced cost from BD or Roche for studies he is conducting. Please see study for all other authors’ relevant financial disclosures.