Human Papillomavirus (HPV) 16 and 18/45 Genotyping-Directed Follow-up of Women With Messenger RNA HPV-Positive, Cytology-Negative Cervical Screening Test Results.

OBJECTIVES: In this study, we sought to correlate genotype test results for human papillomavirus (HPV) types 16, 18, and 45 with histopathologic follow-up diagnoses in patients with messenger RNA (mRNA) high-risk HPV-positive, cytology-negative results. METHODS: We identified 1,157 patients with mRNA HPV-positive, cytology-negative cervical screening test results between June 2015 and June 2018. Reflex HPV 16/18/45 genotype results were documented in 1,018 women aged 30 years or older, 318 of whom had follow-up within 18 months. RESULTS: Histopathologic findings of cervical intraepithelial neoplasia 2 or worse (CIN2+) were diagnosed in 14 of 122 (11.5%) patients positive for HPV 16/18/45 vs in seven of 196 (3.6%) HPV 16/18/45-negative patients. Three patients with high-risk HPV-positive, cytology-negative cervical screening test results were diagnosed with stage I cervical adenocarcinomas following early colposcopic referral and biopsy after HPV 16/18/45-positive genotype results. CONCLUSIONS: Immediate reflex HPV 16/18/45 genotyping of mRNA HPV-positive, cytology-negative patients led to early colposcopic referral and histopathologic diagnoses of three difficult-to-detect, low-stage, cervical adenocarcinomas and significantly increased overall early detection of CIN2+ lesions.

High Fidelity of Breast Biomarker Metrics: A 10-Year Experience in a Single, Large Academic Institution.

PURPOSE: Recommendations for standardization of breast biomarkers including estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) led to the creation of American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines to provide continuous guidance. Included in these recommendations is the "ongoing assay assessment procedures." We report these biomarker metrics as there is a dearth of published information on this topic. MATERIALS AND METHODS: ER, PR, and HER2 positivity rates of all newly diagnosed, recurrent, and metastatic invasive breast cancers on core biopsies, and repeated testing on resection specimen by immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) were collected from April 1, 2008 to December 31, 2017. RESULTS: The positivity rates of ER, PR, and HER2 over almost 10 years of monitoring showed high fidelity. Total ER-positive rate was 83.6% (81.4% to 86.8%), ER+/PR+ was 71.7% (68.6% to 75.5%), ER+/PR- was 17.6% (11.0% to 15.0%), ER-/PR- was 16.0% (13.5% to 18.2%), and ER-/PR+ was 0.6% (0.2% to 1.0%). The HER2-positive rate was 13.7% (10.2% to 17.4%) including 9.9% (7.3% to 11.9%) by IHC and 3.8% (1.9% to 5.9%) by FISH reflexed from IHC 2+ results. FISH amplification rate of HER2 IHC 2+ cases was 11.0% (5.8% to 19.2%). Annual quality-assurance check for HER2 IHC/FISH percent positive and percent negative agreement (as defined by Food and Drug Administration) was 96% to 100%. CONCLUSIONS: This longitudinal active assessment of 9564 breast biomarker cases shows the achievement of high fidelity of breast biomarker results when following the ASCO/CAP guidelines. Continuous monitoring of breast biomarkers may minimize assay analytical drift and assure quality clinically relevant results.

Does discontinuous involvement of a prostatic needle biopsy core by adenocarcinoma correlate with a large tumor focus at radical prostatectomy?

When prostate needle biopsies are involved discontinuously by tumor, no consensus remains on the optimal method of tumor quantification. We investigated whether discontinuous biopsy involvement usually results from a large tumor focus or multiple small foci. Prostate needle biopsies with discontinuous tumor and corresponding whole-mounted radical prostatectomies from 2008 to 2013 were analyzed. Linear length and percentage of biopsy involvement were measured both including and subtracting the benign intervening tissue. The corresponding region of the prostatectomy specimen was evaluated for tumor size and multifocality. From over 800 biopsy sets and 400 prostatectomies performed annually, 40 patients met inclusion criteria. Excluding benign tissue, length and percentage of biopsy involvement ranged from 1 to 7 mm and 5% to 66% (median 2.5 mm, 20%), whereas including intervening tissue yielded 4 to 15.5 mm and 25% to 100%, (median 7 mm, 70%), respectively. Benign intervening tissue measured from 2 to 10.5 mm (median 3.5 mm). In 31 patients (78%), a single tumor focus was present in the corresponding region of the prostate (the dominant tumor in 25/31). In 9 patients, multiple small foci were present. Eleven patients could have been excluded from active surveillance eligibility by measuring tumor from end to end (>50% involvement), of whom only 1 met criteria for clinically insignificant cancer at prostatectomy. Discontinuous tumor in a prostate biopsy often results from a single tumor focus in the corresponding region of the prostate (78%). Therefore, we recommend that an end-to-end measurement be provided, with accompanying diagnostic comment that this often correlates with the size of a single tumor focus.