Retrospective analysis of HPV infection: Cotesting and HPV genotyping in cervical cancer screening within a large academic health care system.

In 2019, the American Society for Colposcopy and Cervical Pathology introduced fundamental shifts toward "risk-based" guidelines, with human papillomavirus (HPV) genotyping as a principal test for investigating squamous intraepithelial lesions. This study aims to provide practice-based evidence and supplement the updated guidelines by investigating HPV demographic distribution and uncovering the pathological features of high-grade squamous intraepithelial lesions (HSILs) caused by high-risk HPV (hrHPV) subtypes. Patients who underwent Papanicolaou screening and HPV testing in two hospital systems over the course of 4 years were recruited. The cytology results were categorized on the basis of the 2014 Bethesda classification. DNA sequences of 14 types of hrHPV were detected by Aptima test. The histological features of HSILs caused by different subtypes were compared between biopsies and excisions. A total of 63,709 cases were included. The HPV prevalence was 14.70%, predominantly in the 30 to 39-year-old age group, with slightly higher rates observed in African Americans. There was no significant racial distribution difference between HPV 16/18/45 and other types. HPV 16/18/45 infection was directly correlated with the severity of abnormal cytology, although the other subtypes were the major causes of cytological abnormalities. The trend for HPV prevalence was consistent across calendar years, and was associated with 8.77% negative for intraepithelial lesion or malignancy, 30.46% atypical squamous cell of undetermined significance, 64.62% low-grade squamous intraepithelial lesion, 66.75% atypical squamous cell-cannot exclude a high-grade squamous intraepithelial lesion, and 91.80% HSIL. Furthermore, 29.09% of HSILs associated with other subtypes were not detectable on subsequent resections. Given the HPV demographic distribution and the histological features of HSILs caused by different subtypes, cotesting with reflex HPV genotyping in specific populations, or expanding the subtypes in the primary HPV screening test, should be considered.

Feng FX ，Birdsong GG ，Wei J ，Dababneh MN ，Reid MD ，Hoskins M ，Wang Q ... -  《-》

Liquid-based cytology and human papillomavirus testing: a pooled analysis using the data from 13 population-based cervical cancer screening studies from China.

The objective of this study was to evaluate the impact of introducing HR-HPV testing in cytology regarding cervical cancer screening practice. A pooled analysis of liquid-based cytology (LBC) and HR-HPV testing using data from 13 population-based cervical cancer screening studies conducted in China was performed. Participants (n=25,404) received LBC and HR-HPV testing. Women found to be positive on screening were referred for colposcopy and biopsy. The effectiveness of screening strategies that use: LBC with HR-HPV triage for atypical squamous cells of undetermined significance (ASC-US), HR-HPV testing with cytology triage for HPV positive tests, or LBC and HPV cotesting was compared with that of LBC screening alone. LBC with HR-HPV triage for ASC-US had similar sensitivity compared with LBC alone, but significantly increased specificity for both cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3 or worse (CIN3+) endpoints, and had the best balance between sensitivity and specificity among the strategies. LBC and HR-HPV cotesting had the highest sensitivity and negative predictive value (NPV) and could permit a safe extension of screening intervals. Through the use of an immediate colposcopy threshold of ASC-US or worse for HR-HPV positive women and the use of a raised threshold of low-grade squamous intraepithelial lesion (LSIL) or worse for HR-HPV negative women, LBC and HR-HPV cotesting could provide the same effectiveness as LBC testing with HR-HPV triage for ASC-US at baseline tests. The results of the current study support the use of the cervical cancer screening guidelines in China.

Pan QJ ，Hu SY ，Guo HQ ，Zhang WH ，Zhang X ，Chen W ，Cao J ，Jiang Y ，Zhao FH ，Qiao YL ... -  《-》

Evaluation of the Use of Methylation as a New Tool for the Diagnostics and Progression of Squamous Intraepithelial Lesions.

Pruski D ，Millert-Kalińska S ，Lis A ，Pelc E ，Konopelski P ，Jach R ，Przybylski M ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Value of intraoperative post-conisation human papillomavirus testing in predicting residual or recurrence after treatment with a loop electrosurgical excision procedure in women with HR-HPV positive and cervical high-grade squamous intraepithelial lesion.

To evaluate the feasibility of intraoperative human papillomavirus (IOP-HPV) testing for the prediction of postoperative treatment failure in patients with high-grade squamous intraepithelial lesion (HSIL) undergoing loop electrosurgical excisional procedure (LEEP). A total of 114 women diagnosed with HSIL by biopsy and/or endocervical curettage who underwent LEEP were included in a prospective cohort study. IOP-HPV testing was performed immediately after the procedure. Patients were followed up for 24 months. Logistic regression was used to analyse the factors influencing the residual or recurrent lesions. Further stratified analyses were performed to investigate the differences in prognosis of IOP-HPV positivity in patients of different age and menopausal status. 1. Of the 114 patients, 6 (5.26%) were pathologically upgraded to cervical cancer, and 21 (18.42%) were lost to follow-up. Recurrence or residual HSIL lesions occurred in 9.20% (8/87) of cases. Of the 8 women who developed post-treatment HSIL, 7 (26.92%) were positive for IOP-HPV, and only 1 (1.64%) was negative for IOP-HPV (< 0.01). 2. Transformation zones of type 2 (P = 0.0306) or type 3 (P = 0.0446), diagnosed as LSIL/negative by cervical biopsy (P = 0.0396), margin involvement (P = 0.0233), positive endocervical curettage after conisation (P = 0.0028), intraoperative HPV-positive (P < 0.01), cytological abnormalities (P = 0.0038), DNA ploidy positivity (P = 0.0172), postoperative HPV (P < 0.01) and DNA ploidy (P = 0.0078) positivity at 6 months were associated with higher risk of residual or recurrent lesions.  3. The results of the multivariate regression analysis showed that IOP-HPV positivity was the independent risk factor for residual or recurrent lesions (OR=10.69 , 95% CI:3.41, 33.51, P<0.01). IOP-HPV positivity was strongly associated with the occurrence of residual/recurrent LSIL (OR=6.42 , 95% CI:1.74, 23.70, P=0.0053) and HSIL (OR=32.08 , 95% CI:3.60, 285.64, P=0.0019). 4. Stratified analyses showed that IOP-HPV positive in patients younger than 50 years or premenopausal patients was associated with a significantly higher risk of recurrence or residual lesions (p<0.05). IOP-HPV positivity is an independent risk factor for residual or recurrent HSIL lesions. In addition, IOP-HPV positivity was more associated with residual or recurrent lesions in those younger than 50 years or premenopausal. IOP-HPV testing may be of critical clinical value in providing the early and accurate prediction of residual or recurrent lesions.

Xia W ，Dai X ，Hu Y ，Yang S ，Chen C ，Li X ... -  《BMC CANCER》

Analysis of the sensitivity of high-grade squamous intraepithelial lesion Pap diagnosis and interobserver variability with the Hologic Genius Digital Diagnostics System.

Artificial intelligence (AI)-based systems are transforming cytopathology practice. The aim of this study was to evaluate the sensitivity of high-grade squamous intraepithelial lesion (HSIL) Papanicolaou (Pap) diagnosis assisted by the Hologic Genius Digital Diagnostics System (GDDS). A validation study was performed with 890 ThinPrep Pap tests with the GDDS independently. From this set, a subset of 183 cases originally interpreted as HSIL confirmed histologically were included in this study. The sensitivity for detecting HSIL by three cytopathologists was calculated. Most HSIL cases were classified as atypical glandular cell/atypical squamous cell-high grade not excluded (AGC/ASC-H) and above by all cytopathologists. Of these cases, 11.5% were classified as low-grade squamous intraepithelial lesion (LSIL) by pathologist A (P-A), 6% by pathologist B (P-B), and 5.5% by pathologist C (P-C); 3.8%, 2.7%, and 1.6% of these cases were classified as atypical squamous cell of unknown significance (ASC-US) by P-A, P-B, and P-C, respectively. The sensitivity for detection of cervical intraepithelial neoplasia 2 and above (CIN2+) lesions was 100% if ASC-US and above (ASC-US+) abnormalities were counted among all three pathologists. The sensitivity for detection of CIN2+ lesions was 84.7%, 91.3%, and 92.9% by P-A, P-B, and P-C, respectively, for ASC-H and above abnormalities. The Kendall W coefficient was 0.722, which indicated strong agreement between all pathologists. New-generation AI-assisted Pap test screening systems such as the GDDS have the potential to transform cytology practice. In this study, the GDDS aided in interpreting HSIL in ThinPrep Pap tests, with good sensitivity and agreement between the pathologists who interacted with this system.

Harinath L ，Elishaev E ，Ye Y ，Matsko J ，Colaizzi A ，Wharton S ，Bhargava R ，Pantanowitz L ，Zhao C ... -  《-》