Negative computer-imaged ThinPrep Pap test and positive hybrid capture2 HPV co-testing results: A quality assurance review.

Women ≥30 years of age with negative (-) Pap tests and positive (+) HPV co-test results have a higher prevalence and cumulative risk of developing high-grade cervical intraepithelial neoplasia (CIN 2+). Thus, the current management in these women is to repeat co-test in 12 months or immediate reflex genotyping for HPV16 or HPV 16/18. If genotyping is not an option, timely quality assurance (QA) rescreen of such Pap tests may be a valuable alternative. All ThinPrep Pap tests (TPPT) interpreted as negative for intra epithelial lesion (NILM) or NILM with reactive cellular changes (NILM/RCC) and a (+) high-risk HPV [Hybrid Capture 2 (HC2), Qiagen, Hilden, Germany] co-test result over a 45-month period (10/2009-06/2013) underwent monthly QA review. The TPPT were screened by the TP Imaging System [TIS, Hologic Inc., Bedford, MA]. Twenty five thousand six hundred and seventy five (18%) NILM and NILM/RCC TPPT of a total of 141,548 TPPT underwent HPV co-test. HPV test was (+) in 2,300 (8.9%) TPPT cases. HPV (+) cases by age group were <30 years, 486 (21%), and ≥30 years, 1,814 (79%). Upon QA review, 10 cases (0.4%) were reclassified, with significant findings in three cases in ≥30 years. Two cases showed high-grade squamous intraepithelial lesion (HSIL) on repeat Pap, and one case showed endocervical adenocarcinoma in situ (AIS) on biopsy. Timely QA review of HPV (+) Pap (-) co-tests is a valuable monitor. Ninety percentage of reclassified cases were in ≥30 age group and 70% were originally signed out by using TIS 22 Field of View (FOV) only. Three reclassified cases had significant findings on follow up (F/U).

The Bethesda System 2001 recommendation for reporting of benign appearing endometrial cells in Pap tests of women age 40 years and older leads to unwarranted surveillance when followed without clinical qualifiers.

OBJECTIVES: The purpose of this study is to determine the impact of the Bethesda System 2001 recommendation of reporting cytologically benign appearing endometrial cells (BEC) seen in Papanicolaou (Pap) tests of all women age 40 years and older, and to determine the significance of such finding. METHODS: Pap tests of women age 40 years and older containing BEC outside of the first half of menstrual cycle reported before and after the Bethesda System 2001 implementation were included. 300 postmenopausal women without BEC were included as control group. Clinical follow-up was reviewed and significant endometrial pathology was defined as simple hyperplasia or a higher diagnosis. RESULTS: BEC reporting rate increased from 0.17% to 0.49% before and after the Bethesda System 2001 (P=0.0001), due to reporting in women with premenopausal status. Significant endometrial pathology was detected in 14 of 121 (11.6%) postmenopausal patients compared to 7 of 300 (2.3%) in the control group (P=0.0002, relative risk=4.96, 95% confidence interval 2.05-11.98), and in none of premenopausal patients. 12 of 14 women with significant endometrial pathology had either postmenopausal bleeding or hormone replacement therapy use. CONCLUSIONS: The Bethesda System 2001 led to increased reporting of BEC only in premenopausal women, leading to biopsies performed solely for BEC in these women with no pathology detected. Presence of BEC in Pap tests of postmenopausal women warrants a thorough clinical review, and immediate biopsy is a valid consideration. Presence of hormone therapy or postmenopausal bleeding may be modifiers of risk.