Ming Guo

A Cross-Sectional Study of the Prevalence of Anal Dysplasia among Women with High-Grade Cervical, Vaginal, and Vulvar Dysplasia or Cancer: The PANDA Study

Background: High-risk human papillomavirus (HR-HPV) infection is a risk factor for anal cancer, yet no anal cancer screening guidelines exist for women with lower genital tract HPV-related disease. We sought to describe the prevalence of anal HR-HPV or cytologic abnormalities in such women. Methods: This cross-sectional study was performed between October 2018 and December 2021. Inclusion criteria were ≥21 years of age and a prior diagnosis of high-grade dysplasia/cancer of the cervix, vagina, or vulva. Participants underwent anal cytology and anal/cervicovaginal HR-HPV testing. Women with abnormal anal cytology were referred for high-resolution anoscopy (HRA). Results: 324 evaluable women were enrolled. Primary diagnosis was high-grade dysplasia/cancer of the cervix (77%), vagina (9%), and vulva (14%). Anal HR-HPV was detected in 92 patients (28%) and included HPV-16 in 24 (26%), HPV-18 in 6 (7%), and other HR-HPV types in 72 (78%) patients. Anal cytology was abnormal in 70 patients (23%) and included atypical squamous cells of undetermined significance (80%), low-grade squamous intraepithelial lesion (9%), high-grade intraepithelial lesion (HSIL; 1%), and atypical squamous cells-cannot rule out HSIL (10%). Of these patients, 55 (79%) underwent HRA. Anal biopsies were performed in 14 patients: 2 patients had anal intraepithelial neoplasia (AIN) 2/3, 1 patient had AIN 1, and 11 patients had negative biopsies. Both patients with AIN 2/3 had a history of cervical dysplasia. Conclusions: Our results suggest an elevated risk of anal HR-HPV infection and cytologic abnormalities in women with lower genital tract dysplasia/cancer. Impact: These results add to the growing body of evidence suggesting the need for evaluation of screening methods for anal dysplasia/cancer in this patient population to inform evidence-based screening recommendations.

Efficacy of Cobas HPV testing for predicting grade 2+ cervical intraepithelial neoplasia in a cancer prevention center and a gynecologic oncology clinic: A single‐institution experience

AbstractBackgroundTo evaluate the efficacy of Cobas human papillomavirus (HPV) testing to predict cervical intraepithelial neoplasia of grade 2 or higher (CIN2+), Cobas HPV testing results were correlated with follow‐up biopsy in patients from Cancer Prevention Center (CPC) and Gynecologic Oncology Clinic (GOC) of The University of Texas MD Anderson Cancer Center.MethodsInstitutional data for patients who underwent Cobas HPV and Papanicolaou (Pap) cytology cotesting from 2019 to 2020 were retrospectively reviewed. Surgical follow‐up results were compared with Cobas HPV testing results in two populations.ResultsA total of 2226 patients, including 921 women (mean age, 55.2 years) seen at the CPC and 1305 women (mean age, 49.3 years) seen at the GOC, were included. Specimens from GOC patients had a significantly higher HPV positivity rate than did those from CPC patients (22.9% vs. 10.1%; p < .001). Cobas HPV testing was positive in all seven CPC patients with surgical follow‐up results showing CIN2+. Among 36 GOC patients with CIN2+ lesions, five patients had HPV−/Pap+ testing results. Although only seven CPC patients had CIN2+, Cobas HPV testing showed 100% sensitivity for predicting CIN2+ in this group. Sensitivity for CIN2+ was 86.5% in the GOC group, whereas 13.9% of GOC patients with CIN2+ had negative HPV testing results.ConclusionsCobas HPV testing was highly efficacious for predicting CIN2+ lesions in the low‐risk CPC population, which supports HPV primary screening for cervical cancer in low‐risk populations. For high‐risk patients, especially those with a history of CIN2+/cervical cancer, HPV/Pap cotesting may still be necessary to maintain a high clinical sensitivity for CIN2+.

Mock Samples That Mimic Human Cervicovaginal Samples to Accelerate the Development and Evaluation of Assays for High‐Risk HPV for Cervical Cancer Screening

ABSTRACT Nearly all cervical cancer cases are caused by high‐risk human papillomavirus (hrHPV) infections. The World Health Organization recommends screening for hrHPV using nucleic acid amplification tests (NAATs) that detect hrHPV DNA or mRNA. Lack of access to affordable, point‐of‐care screening tests in resource‐limited settings leads to women presenting with advanced‐stage cervical cancer, with many dying of the disease. There is a significant need to develop point‐of‐care NAATs to improve screening and early detection. Because access to real clinical samples is limited, initial evaluation of NAATs is often performed using contrived samples created using some combination of extracted hrHPV DNA and/or cultured hrHPV‐positive cells. When mock samples do not adequately recapitulate the contents of clinical cervicovaginal samples, it can delay clinical translation of potentially promising assays. To improve the value of contrived samples, we characterized the composition of 32 hrHPV DNA‐positive cervicovaginal clinical samples. We also describe a simple method to generate contrived samples that mimic the diversity of clinical cervicovaginal samples, and test them using the methods used to characterize the clinical samples. Results show that the hrHPV DNA content of cervicovaginal samples varies by approximately eight orders of magnitude and spans from 100% linear integrated DNA to 100% circular non‐integrated DNA, that the concentration of hrHPV mRNA also varies by nearly nine orders of magnitude between patient samples, and that the concentration of potential inhibitors such as hemoglobin varies by more than three orders of magnitude. hrHPV DNA and mRNA extracted from contrived samples exhibited expected patterns of DNA quantity, DNA conformation, and mRNA quantity. Altogether, the protocols described here to generate mock samples can help NAAT developers optimize test performance prior to clinical evaluation, potentially improving test performance and reducing time to deployment.