Post-Loop Electrosurgical Excision Procedure High-Risk Human Papillomavirus Testing as a Test of Cure: The British Columbia Experience.

OBJECTIVES: To determine whether Hybrid Capture 2 High-Risk HPV DNA Test (HC2) can be used as a test of cure in women treated for cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) and allow discharge from colposcopy follow-up with a return to a cytology-based screening program for HC2-negative women. MATERIALS AND METHODS: Data were analyzed for all women who underwent a loop electrosurgical excision procedure between August 1, 2008, and June 30, 2011, and had a valid HC2 result after loop electrosurgical excision procedure and follow-up histopathology result, to determine risk of persistent or recurrent CIN 2+ in HC2-positive and HC2-negative women. RESULTS: Two thousand three hundred forty women had adequate biopsies and valid HC2 results. Of 460 HC2-positive women, 118 (25.7%) were diagnosed with CIN 2+, whereas of 1,880 HC2-negative women, 35 (1.9%) had a subsequent diagnosis of CIN 2+ (p < .0002) yielding a HC2-negative predictive value of 98.1% (95% confidence interval = 97.4-98.7). Of 460 HC2-positive women, 306 initially had negative biopsies. In the subsequent 36 months, 38 of the 306 were diagnosed with CIN 2+. CONCLUSIONS: We conclude that women with a negative HC2 test can safely return to routine annual cytology screening by primary care providers while women who test HC2 positive are at higher risk and should continue to be followed by colposcopy, even if their initial biopsy is negative.

Comparative performance of human papillomavirus messenger RNA versus DNA screening tests at baseline and 48 months in the HPV FOCAL trial.

BACKGROUND: HPV FOCAL is a randomized trial comparing high-risk HPV [Hybrid Capture 2 (HC2)] vs. liquid-based cytology (LBC) for primary cervical screening. OBJECTIVE: The present study objective was to compare Aptima HPV (AHPV) and HC2 assay performance at the intervention arm baseline and 48 mo. screens in relation to the rates of cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+). STUDY DESIGN: Women enrolled after December 2010 (n = 3475) were screened at baseline with both AHPV and HC2 (AHPV was blinded). Women with CIN2+ exited the trial; HC2 negative (-) women and those HC2 positive (+) with

Interobserver agreement for assessing invasion in stage 1A vulvar squamous cell carcinoma.

Invasive squamous cell carcinoma of the vulva with ≤1 mm stromal invasion is classified as stage 1A. Cancer staging systems state that the depth of invasion should be measured from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of the invasive tumor. Measurement of the depth of invasion guides patient management. Even though this measurement is critical, no studies have reported the reliability among pathologists for determining the cutoff point of ≤1 mm stromal invasion in vulvar cancer. We assessed agreement among pathologists for determining whether a vulvar tumor is invasive, for the depth of invasion, and for tumor thickness. Forty-five cases of vulvar squamous cell carcinoma with a depth of invasion of ≤5 mm were chosen. Eleven gynecologic pathologists independently reviewed the slides and, for a subset of cases, pictorially recorded measurements on photographs. The number of cases that were reported as invasive by the 11 pathologists ranged from 21 to 44. The number of cases that were reported as showing a depth of invasion of ≤1 mm ranged from 7 to 27. Eight pathologists provided measurements for all lesions reported as invasive, the remaining 3 pathologists stated that they were unable to measure 2, 7, and 16 lesions, respectively. Mean κ for diagnosing vulvar carcinoma as invasive was 0.24 and for measuring the depth of invasion and thickness was 0.51 and 0.49, respectively. There was only fair agreement in determining whether the lesion was invasive. In cases in which pathologists agreed upon the diagnosis of invasion, agreement on depth was moderate. When using the recommended cancer staging method, interpretation of the location of the most superficial dermal papilla varied among pathologists. Measuring thickness did not improve agreement. This is the first study that has assessed the reliability of the diagnosis of invasion in vulvar cancer among gynecologic pathologists, the interobserver agreement for reporting the critical 1 mm threshold of depth of stromal invasion, and the way in which the International Federation of Gynecology and Obstetrics method is used by pathologists.

Reproducibility of the histological diagnosis of cervical dysplasia among pathologists from 4 continents.

The reliable histological diagnosis of cervical squamous intraepithelial lesions (SILs), especially low-grade SIL, is known to be problematic. Poor diagnostic reproducibility can complicate studies addressing its appropriate management. As part of an international study comparing expectant management of histologically proven low-grade SIL with immediate loop electrocautery excisional procedure, this study was carried out to assess interobserver agreement on the histological diagnosis of SILs among a group of 22 pathologists from 5 countries and the intraobserver reliability among a subset of 7 Canadian pathologists. Fifty-six histological slides from colposcopically obtained cervical biopsies were circulated to each of the 22 pathologists. To assess intraobserver reliability, 7 Canadian pathologists assessed 40 of the slides once and 16 of the slides twice. Kappa values were used to measure interobserver agreement with an overall kappa value of 0.61 (95% confidence interval, 0.60-0.62) corresponding to moderate reliability. The weighted kappa values for interobserver agreement ranged from 0.46 to 0.88 (median, 0.79). The intraobserver reliability of 7 Canadian pathologists ranged from substantial to excellent based upon the weighted kappa values ranging from 0.62 to 0.94 (median, 0.72). This degree of reliability is comparable to that found in similar studies. In an individual case, there can be considerable disparity in diagnosis that can result in disparate management strategies. This adds a layer of complexity to any trial that attempts to assess optimal treatment strategies or the natural history of this disease.