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Objective The aim of the study was to evaluate the Cobas 4800 Assay and the SeqHPV Assay with self (S) and direct (D) cervical samples in the Chinese Multicenter Screening Trial (CHIMUST). Materials and methods The CHIMUST is a large population-based multicenter clinical trial, and 10,885 women aged 30-59 years from 15 sites in 7 provinces with no cervical cancer screening for 3 years were eligible. All participating women contributed one self-collected sample (S) and 1 physician-collected endocervical sample (DL). The self-collected sample was first applied to the solid media transport card (SS), and then, the brush placed in 6 mL of ThinPrepSolution (SL). All samples were tested with Cobas 4800 and SeqHPV high-risk HPV assays. Patients human papillomavirus positive (self or direct) were recalled for colposcopy and biopsies. Results A total of 10,399 women had complete data. The mean age was 43.9 years. A total of 1.4% (142/10,399) had cervical intraepithelial neoplasia (CIN) 2+ and 0.5% (54/10,339) had CIN 3+. In the liquid specimens, the overall HPV infection rates were 10.8% for Cobas and 10.9% for SeqHPV in D sample, and 13.7% for Cobas and 11.6% for SeqHPV in SL sample, respectively. The sensitivity of Cobas-DL, Cobas-SL, SeqHPV-DL, and SeqHPV-SL for CIN 2+ was 95.07%, 95.07%, 94.33%, and 96.48%, respectively. The specificity of Cobas-DL, Cobas-SL, SeqHPV-DL, and SeqHPV-SL for CIN 2+ was 90.38%, 87.35%, 90.21%, and 89.53%, respectively. There were no differences in sensitivity when applying the 2 assays to both self- and directly collected samples in liquid transport media (p > .05). Conclusions Both Cobas and SeqHPV screening assays using both self-collected and directly endocervical collected specimens demonstrate similar sensitivity for the detection of CIN 2+ and CIN 3+.

OBJECTIVE The aim of the study was to assess whether lower proportions of cervical intraepithelial neoplasia 2+ diagnosed by random biopsy are from lower cut points defining an abnormal colposcopic impression or obtaining only one random biopsy when colposcopic impression is normal. METHODS We compared colposcopy experiences within Shanxi Province Cervical Cancer Screening Study (SPOCCS) (n = 1,383) and Shenzhen Cervical Cancer Screening Trial (SHENCCAST) (n = 631), which had instructive differences in the cut point defining an abnormal colposcopic impression. RESULTS The proportion of CIN 2+ diagnosed by random biopsy in SPOCCS (35.0%, 141/403) was higher than SHENCCAST (18.4%, 35/190, p < .001). Quadrant-specific receiver operating characteristic curves for diagnosis of CIN 2+ by colposcopic impression in SPOCCS and SHENCCAST were similar; a lower cut point for an abnormal colposcopic impression in SHENCCAST resulted in lower proportion of CIN 2+ diagnosed by random biopsy. Normal colposcopic impression was found in 85.1% (120/141) of cases of CIN 2+ diagnosed by random biopsy in SPOCCS and in 57.1% (20/35) of such cases in SHENCCAST. Of CIN 2+ diagnosed by random cervical biopsy with normal colposcopic impression, one cervical quadrant was involved with CIN 2+ in 66.7% (80/120) of colposcopies in SPOCCS and 80% (16/20) of colposcopies in SHENCCAST. CONCLUSIONS Colposcopy series with higher proportions of CIN 2+ diagnosed by random biopsy likely have more stringent cut points defining an abnormal colposcopic impression and have more random biopsies when the colposcopic impression is normal. At colposcopy, we advise multiple biopsies of all acetowhite epithelium or multiple random biopsies to increase the sensitivity of colposcopy.

The goal of this study was to use the biomarkers human papillomavirus (HPV) L1 and p16 to develop an algorithm that could triage the individual patient with CIN1 at risk for progression. A total of 82 patients initially diagnosed with CIN1 at Peking University Shenzhen Hospital in China had their initial and follow-up paraffin-embedded tissue blocks immune-stained for HPV L1 capsid protein and p16. For CIN1, any staining of abnormal epithelium was considered positive. All patients were followed until they developed CIN2+ or for ≥3 years. About 38 patients regressed (HPV-, Cytology-), 17 persisted (CIN1), and 27 progressed (≥CIN2+). At initial diagnosis, HPV L1 capsid protein was expressed in 42.7% of the CIN1 cases. There was no difference in L1 expression among the 3 groups. However, p16-positive staining in the progression group was significantly higher than in the regression group (P

The aim of the study was to evaluate the human papillomavirus (HPV) viral load combined with cytology as a secondary screening strategy after primary HPV screening.The data referring to direct Hybrid Capture 2 (HC2), cytology, and histology from Shenzhen Cervical Cancer Screening Trial II were re-analyzed to determine the correlation between viral load and cervical lesions. In addition, algorithms using different viral loads as cut points for immediate colposcopy plus cytology triage were compared with several recommended or controversial primary screening methods.A total of 8,556 women with a mean age of 38.9 years were included in the analysis, of which 13.67% tested high-risk HPV positive with a prevalence of 2.72% for cervical intraepithelial neoplasia 2+ (CIN 2+) and 1.65% for CIN 3+. A significant correlation was observed between increasing relative light units/control (RLU/CO) values and worsening cervical lesions. The mean RLU/CO values for negative, CIN 1, CIN 2, CIN 3, and cancer were 6.86, 119.43, 410.90, 449.39, and 853.26, respectively. A larger proportion of HPV infections with relative high viral load (≥10 RLU/CO) were found in higher-grade lesions. The algorithm using 10 or greater RLU/CO as cut point for immediate colposcopy followed by triage cytology for the other positive (≥110 RLU/CO) had sensitivity of 93.13%/96.45% and specificity of 92.32%/91.44% for CIN 2+/3+, and the colposcopy referral rate was 10.00%.Human papillomavirus viral load level is positively associated with cervical lesion grade. Ten relative light units/control or greater is a viable threshold for immediate colposcopy whereas 1 or greater or less than 10 RLU/CO is advised to reflex cytology for optimizing sensitivity and specificity, as well as referral rates.

The aim of the study was to determine whether p16 positive/cervical intraepithelial neoplasia (CIN) 2, 3, and cancer (p16 + CIN 2/3+) detected by colposcopy-directed or random biopsy differ by age, referral cytology, human papillomavirus (HPV) 16, and lesion size.Data from the Shenzhen Cervical Cancer Screening Trial II where, at colposcopy, women who had directed and random cervical biopsies were reviewed to find women with CIN 2, 3, or cancer; 227 such women identified had their paraffin-embedded tissue blocks recut, reviewed, and then immune stained for p16. Data were analyzed by χ, Fisher exact test, and linear regression.After histopathologic review and p16 staining of CIN 2, 175 women were diagnosed with p16 + CIN 2/3+. When compared with those diagnosed by colposcopy-directed biopsy (n = 138), those diagnosed by random biopsy (n = 37) were more likely to have Cytology-Lo (cytology of negative, atypical squamous cells of undetermined significance, or low-grade squamous intraepithelial lesion; p = .07), less likely to have HPV 16 (p = .041), more likely to be 51 years or older (p = .022), and more likely to have 1 quadrant lesions (p.001). Logistic regression analysis showed p16 + CIN 2/3+ diagnosed by random biopsy was predicted by 1 quadrant lesions (p.0001) and age of 51 years or older (p = .03) but not by Cytology-Lo (p = .71) nor HPV 16 (p = .26).Women with p16 + CIN 2/3+ diagnosed by random biopsy are older and less likely to have HPV 16; hence, CIN diagnosed by random biopsy may not be as virulent as CIN diagnosed by colposcopy-directed biopsy. Regardless, we advise that CIN diagnosed by random biopsy be viewed like CIN diagnosed by colposcopy-directed biopsy.

Objective The aim of this study was to determine if there is a different p16 expression pattern between colposcope-directed and random (colposcope-undetectable) biopsies of cervical intraepithelial neoplasia (CIN2) and CIN3. Methods Cervical biopsies that were positive for CIN2 or CIN3 were selected from a database of samples acquired during a large population-based clinical trial in Guangdong Province in China (Shenzhen Cervical Cancer Screening Study II). Blocks were recut, reread, and then immunostained for p16. Biopsies were categorized as either colposcope-directed or random biopsies. Diffuse staining was considered p16 positive, whereas focal or no staining was considered p16 negative. Differences were determined by the Fisher exact test. Results Among the patients with CIN3, there were 232 individual biopsies of CIN3. Sixty were randomly collected, and 172 were colposcopy directed. p16 positivity for the colposcope-directed and random biopsies was 97.7% and 91.7%, respectively (p = 0.052). Like the CIN3 biopsies, colposcope-directed and random CIN2 samples expressed p16 similarly (86.8% [46/53] and 82.6% [19/23], p = .73, respectively). Conclusions Based on our data, even small colposcope-undetectable biopsies of CIN3 are significant. Random biopsies of CIN2 or CIN3 demonstrate similar p16 positivity as visible lesions and therefore might be expected to have a similar natural history.

Objectives To determine a management strategy for women testing negative with cervical cytology and positive for high-risk human papillomavirus (HR-HPV). Methods Using the data from the large population-based Shenzhen Cervical Cancer Screening Trials II and III (SHENCCAST II/III), we compared the risk for cervical intraepithelial neoplasia grade 3 or cancer (CIN 3+) in women with negative cytology but testing positive for HR-HPV DNA using Cervista HPV HR or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF), followed by secondary screening with type-specific Cervista HPV-16/18 or MALDI-TOF. The study aim was to seek the most sensitive and specific triage assay for referral for colposcopy. Results A total of 8,556 women had complete data. The proportion of women with negative cytology and positive HR-HPV by Cervista HR-HPV (5.30%, 453/8,556) was slightly lower than that of women with negative cytology and HR-HPV-positive tests by MALDI-TOF (5.82%, 499/8,556, p = .015). The proportion of women having negative cervical cytology and a positive HR-HPV by Cervista HR who have HPV-16 and/or -18 by Cervista HPV-16/18 (11.8%, 53/448) was less than that of women with a negative cervical cytology and positive HR-HPV by MALDI-TOF who have HPV-16 and/or -18 by MALDI-TOF (19.4%, 97/499, p = .001). The proportion of CIN 3+ within negative cervical cytology and positive HR-HPV that were HPV-16 and/or -18 for the Cervista 16/18 assay (61.5%, 8/13) was similar to that for the MALDI-TOF 16/18 assay (66.7%, 10/15, p = 0.8). Conclusions In the cytology-negative HR-HPV-positive population, Cervista 16/18 as the HPV detection method would refer 11.8% of women for colposcopy and diagnose 61.5% of the CIN 3+, while MALDI-TOF16/18 would refer 19.4% and diagnose 66.7% of the CIN 3+. Cervista HPV-16/18 seems to be the superior triage test. However, in resource-limited settings, an assay that includes 16/18 genotyping in the primary result (rather than a second test) may be more cost efficient.

Objective We recently demonstrated that a self-collected sample tested with a high-throughput polymerase chain reaction-based high-risk human papillomavirus (HR-HPV) assay is equal in sensitivity to a physician-obtained direct endocervical sample. We now explore some secondary screening options to improve specificity. Methods The Shenzhen Cervical Cancer Screening Trial II is a multisite, population-based cross-sectional cervical cancer screening study conducted in Guangdong Province, China. Two HR-HPV assays were used for self-collected specimens, and 3 assays were used for directly collected specimens along with cytology. The polymerase chain reaction-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay reported 14 HR-HPV types. Any patient with a positive lesion on any assay or cytology underwent colposcopy and biopsy. Results A total of 8,556 women with a mean age of 38.9 years (range = 25-54 years) were included in the analysis. Primary self-collection had a sensitivity of 94.3% and a specificity of 87.5% (for cervical intraepithelial neoplasia grade 3 or cancer). Secondary cervical cytology had a sensitivity and specificity of 83.0% and 95.2%, respectively, which would require a pelvic examination and sacrifice some sensitivity. Secondary genotyping for HPV types 16 or 18 had a sensitivity and specificity of 53.9% and 97.7%, respectively; and HPV types 16, 18, 31, 33, 45, 52, and 58 had a sensitivity and specificity of 92.2% and 90.4%, respectively. Conclusions Genotyping is efficient if it is part of the primary test result. It potentially identifies a high percentage of the cancers (types 16/18 = 84.5% in China).