Kinetic and Thermodynamic Characteristics of Torrefied Acer palmatum.

The goal of this research was to investigate the effects of torrefying temperature (220, 260, and 300 °C) on the physicochemical properties, kinetics, thermodynamic parameters, and reaction processes of Acer palmatum (AP) during the pyrolysis process. The kinetics of raw materials and torrefied biomass were studied by using three kinetic models, and the main function graph approach was employed to find the reaction mechanism. The torrefied biomass produced at temperatures of 220 °C (AP-220), 260 °C (AP-260), and 300 °C (AP-300) was thermogravimetrically analyzed at four different heating rates (5, 10, 15, and 20 °C/min). In comparison to the raw material, the average activation energy of torrefied biomass declined with increasing temperature, from 174.13 to 84.67 kJ/mol (FWO), 172.52 to 81.24 kJ/mol (KAS and DAEM). The volatile contents of AP and AP-220 are higher than those of AP-260 and AP-300, indicating that the random nucleation model occupies the central position. Compared with the raw biomass, the average Gibbs free energy (ΔG) of torrefied biomass increased from 157.97 to 195.38 kJ/mol. The mean enthalpy change (ΔH) during the torrefaction process is positive, while the mean entropy change (ΔS) of the torrefaction of biomass is negative, decreasing from 16.93 to -151.53 kJ/mol (FWO) and from 14.36 to -156.06 kJ/mol (KAS and DAEM). Overall, the findings provide a comprehensive understanding of the kinetics and improved features of torrefied biomass as a high-quality solid fuel.

Design and Implementation of a Chain-Type Direct Push Drilling Rig for Contaminated Sites.

For sites where volatile organic compounds are present, the direct push method, in combination with other sensors for investigation, is a powerful method. The investigation process is an integrated drilling and sensing process, but the trajectory of the probe carrying the sensor is ambiguous. This paper explores and introduces the application of a chain-type direct push drilling rig by designing and building a chain-type direct push miniature drilling rig. This rig allows for indoor experimental studies of direct push trajectories. The chain-type direct push drilling model is proposed based on the mechanism of chain transmission. The drilling rig provides a steady direct thrust through the chain, which is driven by a hydraulic motor. In addition, the drilling tests and results described prove that the chain could be applied to direct push drilling. The chain-type direct push drilling rig can drill to a depth of 1940 mm in single-pass and up to 20,000 mm in multiple passes. The test results also indicate that it drills a total length of 462.461 mm and stops after 87.545 s of operation. The machine can provide a drilling angle of 0-90° and keep the borehole angle fluctuating within 0.6° with the characteristics of strong adjustability, flexibility, continuity, stability, and low disturbance, which is of great value and significance for studying the drilling trajectory of direct push tools and obtaining more accurate investigation data.

[Effectiveness of Different Testing Strategies Applied for Cervical Cancer Screening in Shuangliu District, Chengdu City].

Objective: To evaluate the clinical value of different combination strategies of high-risk HPV (hr-HPV) testing and Thinprep cytology test (TCT), a cervical cytology test, for cervical cancer screening, especially for high or higher-grade squamous intraepithelial lesion (HSIL+) in Shuangliu District, Chengdu City. Methods: The study is a population-based randomized clinical trial. Women aged 35 to 65 years meeting the inclusion criteria were enrolled for the study. At the baseline screening conducted in the first year, the participants were randomly assigned to either cytology test or hr-HPV testing at a ratio of 1∶2. If the paticipants had positive results for the baseline hr-HPV test, they would then undergo either cytology test or colposcopy by random assignment. After 24 months, all participants were called back, and combined screening of cytology test and hr-HPV test were performed. Women who had negative results at baseline screening and who entered and completed the third-year follow-up were selected as the subjects of the study. Based on the aforementioned testing findings, the related data were extracted and four different screening protocols were simulated: 1) combined TCT and hr-HPV screening, with referral for colposcopy when there was positive results for either one of the two; 2) combined TCT and hr-HPV screening, with referral for colposcopy when both tests had positive results at the same time; 3) TCT was done for preliminary screening and those who were found to be positive would then undergo hr-HPV test for triage purpose, with subsequent referral made for colposcopy if the hr-HPV results were positive; 4) hr-HPV was done for preliminary screening and those who were found to be positive would then undergo TCT, with subsequent referral made for colposcopy if TCT results were positive. With the detection of HSIL+ on histological examination as the endpoint event, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve ( AUC) of different combination screening models were calculated. Results: A total of 3102 women were screened, and 2967 women were included in the statistical analysis in this study. Among the 2967 women, 979 were randomized to cytology and 1988 to hr-HPV genotyping. For prescreening, the positive rate of the cytology group was 5.6% (55/979), with of HSIL+ positive rate being 0.2% (2/979), while the positive rate of the hr-HPV group was 7.5% (149/1988), with HSIL+ positive rate being 0.9% (18/1988). After 24 months, 2456 women were called back and were given cervical cytology test and hr-HPV test at the same time. Among them, the positive rate of the cytology group was 3.2% (78/2456), while the positive rate of hr-HPV group was 8.7% (215/2456). The overall positive rate of HSIL+ was 0.69%(17/2456). Women with a negative baseline hr-HPV had a lower incidence of HSIL+ lesions in the long term. The strategy of cervical cytology screening combined with hr-HPV test for triage purpose is the best method, with a sensitivity of 88.9%, a specificity of 58.3%, a PPV of 44.4%, a NPV of 93.3%, and an AUC of 0.736, P=0.039 (95% CI: 0.555-0.917). Conclusion: This randomized clinical trial from Shuangliu District, Chengdu City shows that the sensitivity of hr-HPV testing is better than that of cytology test, and the prevalence of HSIL+ in women with negative baseline hr-HPV results is lower than that of women with negative baseline cytology results. The screening program of TCT for prescreening plus subsequent hr-HPV test for triage purpose shows better value for the detection of HSIL+.

Potential clinical value of interleukin-31 and interleukin-33 with their receptors expression as diagnostic and predictive factors in endometrial cancer: a case-control study.

Aims: To evaluate the potential role of interleukin-31 and interleukin-33 in diagnosis and prognosis from endometrial cancer. Methods: Tissue samples and clinical data were collected from 260 patients with endometrial cancer and 150 control patients with benign uterine diseases. Immunohistochemistry and ELISA testing quantified the expressions of interleukin-31 and interleukin-33 and their receptors. After surgery, all patients were followed up for an average of 56.3 months. Surgical effects were evaluated based on the patients' symptoms and signs. A two-sided P value <0.05 was considered significant. Results: IL-31, IL-33 and their receptors were significantly accumulated with the progression of endometrial cancer, in comparison to the controls. Moreover, the expressions were correlated with clinical characteristics, including tumor stage, differentiation, and associated with patients' disease-free survival. Conclusions: Limited data was available between the expressions of IL-31 and IL-33 and the receptors in patients with endometrial cancer. Our study findings suggested that the expressions of IL-31 and IL-33 might become possible biomarkers for the diagnosis and prediction in endometrial cancer.

The Performance of Immunocytochemistry Staining as Triaging Tests for High-Risk HPV-Positive Women: A 24-Month Prospective Study.

It is urgent to develop an accurate approach to improve the predictive performance of hrHPV-based screening. The aim is to evaluate the performance of p16/Ki-67 and p16/MCM2 staining to triage high-risk human papillomavirus- (hrHPV-) positive women. Cervical specimens were collected from eligible women and tested for hrHPV genotyping, cytology, p16/Ki-67, and p16/MCM2 staining at baseline. Women were invited to participate in follow-up screening by cytology and hrHPV testing at 24 months. Positive women received colposcopy and biopsies. Histopathological diagnoses were the gold standard. 485 women came back for the follow-up screening. The positive rate of p16/Ki-67 was 20.2% and of p16/MCM2 was 27.2%. The positive rates of p16/Ki-67 ( P < 0.001) and p16/MCM2 (P=0.021) were increased by the severity of histopathology findings. Among hrHPV-positive women, the sensitivity, specificity, PPV, and NPV for p16/Ki-67 were 90.9%, 67.0%, 16.5%, and 99.0%, and for p16/MCM2 were 81.8%, 43.1%, 9.4%, and 97.1%. The sensitivity of cytology for triaging hrHPV-positive women were lower than p16/Ki-67 (P=0.012) and p16/MCM2 (P=0.065). The cocktail staining did not add sensitivity to p16/Ki-67 or p16/MCM2 staining alone (P > 0.05), however, cutting down the specificity of p16/Ki-67 staining alone with statistical significance (67.0% vs. 40.2%, P < 0.001). The risk of CIN2+ within 24 months for hrHPV-positive but triaging negative women at baseline was 0.5 (0.1-2.7), 0.7 (0.1-4.1), and 2.4 (1.1-5.0) for p16/Ki-67, p16/MCM2, and cytology, respectively. As an objective and accurate immunocytochemical staining, the p16/Ki-67 and p16/MCM2 dual staining performed better than cytology to triage positive hrHPV. On condition that high-quality cytology is unavailable, immunocytochemical staining by p16/Ki-67 or p16/MCM2 is an option for triaging hrHPV-positive women. The combination of p16/Ki-67 and p16/MCM2 could not improve the accuracy in detecting CIN2+.

Multi-Infection Patterns and Co-infection Preference of 27 Human Papillomavirus Types Among 137,943 Gynecological Outpatients Across China.

Background: The epidemiological feature of human papillomavirus (HPV) infection is distinctive in China. We aimed to investigate the multi-infection patterns and co-infection preference of 27 HPV types among gynecological outpatients across China. Methods: Overall 137,943 gynecological outpatients were recruited from eight tertiary hospitals located in seven regions of China, between July 1st, 2014 and December 31st, 2016. The overall, region-specific, age-specific and type-specific prevalence of HPV infection were calculated, respectively. The pattern of HPV infection was also evaluated. Furthermore, rate ratio was calculated to evaluate the co-infection preference of any two HPV genotypes. Results: The overall prevalence of 27 HPVs' [17 high-risk (hr)/10 low-risk (lr)] infection was 23.5%. The age-specific HPV prevalence showed a "U-shaped" pattern. The most prevalent hrHPV genotypes were 16, 52, and 58. Multiple infections were detected in 25.8% of the HPV-positive women, in which dual infection was more prevalent. HPV 16/18 were likely to co-infected with HPV 31 but unlikely with HPV 52/58, i.e., the co-infection of HPV 16 with HPV 31 was high (3.5-fold), but low for HPV 58 (1.8-fold), and 52 (1.2-fold), while the co-infection of HPV 18 with HPV 31 was high (4.3-fold), but low for HPV 52 (1.9-fold), and 58 (1.7-fold). Conclusions: We found age-specific prevalence of HPV infection showed a "U-shaped" pattern for high and low risk HPV, suggesting the importance of screening among younger women and the necessary of detection among older women. We found a novel co-infection preference of HPV 16/18 with 31, 52, and 58, suggesting a need of developing and marketing prophylactic HPV vaccines that protect against more genotypes in China.

Performance of HPV Genotyping Combined with p16/Ki-67 in Detection of Cervical Precancer and Cancer Among HPV-Positive Chinese Women.

Women with positive high-risk human papillomavirus (hrHPV) need efficient triage testing to determine colposcopy referrals. Triage strategies of combining p16/Ki-67 with extended HPV genotyping were evaluated in this study. In total, 899 women attending cervical cancer screening program and 858 women referred to colposcopy from five hospitals were recruited. All the participants were tested by HPV assays and p16/Ki-67 dual staining. Colposcopy and biopsy were performed on women with any abnormal results. HPV genotypes were divided into four strata (HPV16/18, HPV31/33/58/52, HPV45/59/56/66, and HPV51/39/68/35) according to their risks for cervical intraepithelial neoplasia grade 3 or worse (CIN3+). The positive rates of four genotype strata among CIN3+ women were 3.47% (HPV51/39/68/35), 7.73% (HPV45/59/56/66), 14.7% (HPV31/33/58/52), and 78.1% (HPV16/18), respectively (P trend < 0.001). The positive rates of p16/Ki-67 increased with the elevation of HPV risk hierarchical from 65.0% in HPV51/39/68/35-positive women to 88.0% in HPV16/18-positive women (P trend < 0.001). p16/Ki-67 was an effective method for risk stratification of CIN2+ among HPV31/33/58/52- and HPV45/59/56/66-positive women [HPV31/33/58/52: OR for dual stain+ (ORDS+) of 26.7 (16.8-42.4) and OR for dual stain- (ORDS-) of 3.87(1.89-7.91); HPV45/59/56/66: ORDS+ of 10.3(5.05-21.0) and ORDS- of 1.27(0.38-4.26)]. The combination of HPV16/18 genotyping and p16/Ki-67 triage of HPV31/33/58/52/45/59/56/66-positive women resulted in a lower referral rate (40.1% vs. 41.3%; P < 0.001) as compared with triage of 12 other HPV-positive women with p16/Ki-67, although sensitivity and specificity levels for these two strategies were identical. Combining HPV extended genotyping and p16/Ki-67 can be considered as a promising strategy for cervical cancer screening and triage.

Genome-Wide Profiling of Long Noncoding RNA Expression Patterns in Women With Repeated Implantation Failure by RNA Sequencing.

OBJECTIVES: To compare long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression levels in endometrium between patients with repeated implantation failure (RIF) following in vitro fertilization (IVF)-embryo transfer and control women. MATERIALS AND METHODS: RNA sequencing (RNA-seq) and alignments were performed to identify lncRNAs and mRNAs using endometrial samples collected from 3 patients and 3 control women. A subset of 10 differentially expressed lncRNAs and 6 mRNAs were validated in all participants using quantitative reverse transcription polymerase chain reaction. The potential biological roles of identified lncRNAs were predicted via coexpressed mRNA annotations. Twenty patients with RIF and 30 control women were recruited for validation. RESULTS: We identified 1202 differentially expressed genes, including 742 lncRNAs and 460 mRNAs, in mid-secretory phase endometrial tissue from patients with RIF following IVF compared to control women. We analyzed the target genes of the lncRNAs and uncovered 148 lncRNAs corresponding to 147 cis-regulated target genes. The cis-regulated target genes of these significantly differentially expressed lncRNAs were clustered into several pathways, such as the tumor necrosis factor signaling pathway, the Toll-like receptor signaling pathway, and the NF-kappa B (NF-κB) signaling pathway. CONCLUSION: Our study constitutes the first report on the investigation of the regulatory mechanisms of lncRNAs in endometrial receptivity in women experiencing RIF using RNA-seq. Our results provide a valuable candidate reservoir for future functional studies of lncRNAs.

Clinical evaluation of human papillomavirus 16/18 oncoprotein test for cervical cancer screening and HPV positive women triage.

HPV-16 and -18 account for about 80% of cervical cancers. We evaluated the performance of HPV-16/18 oncoprotein to predict precancer and cancer in corresponding tissue biopsy specimens. 1,008 women attending cervical cancer screening program and 638 women referred to colposcopy with biopsy-confirmed cervical intraepithelial neoplasia grade 2 or worse (CIN2+) from 4 hospitals were recruited (1,646 in total). All women were tested OncoE6 (AVC), Liquid-Based Cytology (Hologic) and cobas HPV test (Roche). Colposcopy was performed on women with any abnormal results. The final diagnoses were based on a consensus panel review of the histology. There were 919 normal, 69 CIN1, 53 CIN2, 91 CIN3,474 squamous cell carcinoma(SCC) and 40 adenocarcinoma (ADC) cases, the prevalence of OncoE6 was 1.7%, 10.1%, 13.2%, 44.0%, 80.4% and 65.0%, respectively. The percent positive for cobas was higher than that of OncoE6 in detection of HPV16/18 in entire population (p < 0.001). However, the disparity of positive rate between these two tests became tiny among cervical cancer patients (CIN2: 26.4% vs. 13.2%, CIN3: 73.6% vs. 44.0%, SCC: 84.0% vs. 80.4%, ADC: 67.5% vs. 65.0%). OncoE6 was less sensitive than cobas (73.9% vs. 93.6%, p < 0.001), but more specific (97.1% vs. 75.4%, p < 0.001) for CIN3+ in entire population; OncoE6 yielded a sensitivity of 77.7% and a specificity of 91.0% for CIN3+ among cobas positive women, which can reduce nearly half of the colposcopy referral numbers. OncoE6 can be considered as a useful tool for cervical cancer screening and a potential powerful biomarker for HPV positive triage.

The effect of p16/Ki-67 and p16/mcm2 on the detection of cervical intraepithelial neoplasia: a prospective study from China.

2,067 women who underwent cervical cancer screening were included in this study. p16/Ki-67 and p16/mcm2 were performed on the remaining liquid-based cytology (LBC) samples of 125 HPV-positive women and 114 randomly selected HPV-negative women. Women with HR-HPV infection or cytological abnormalities (≥ASC-US) were referred for colposcopy and biopsy. A third-year follow up visit was performed on all women except for CIN2+. The expression of p16/Ki-67 and p16/mcm2 in the HPV16/18 group and in the other 12 HR-HPV group was significantly higher than that in HPV negative group (P<0.05), with odds ratios (ORs) of 16.27 (95% CI: 4.38-60.47) and 4.52 (95% CI: 2.16-9.45) for p16/Ki-67, and 31.28 (95% CI: 6.33-154.56) and 9.10 (95% CI: 4.52-18.33) for p16/mcm2, respectively. The sensitivities to detect CIN2+ and CIN3 + were 94.1% (95% CI: 73.0-99.0) and 92.9% (95% CI: 68.5-98.7) for p16/Ki-67, and 88.2% (95% CI: 65.7-96.7) and 85.7% (95% CI: 60.1-96.0) for p16/mcm2, respectively. Both the sensitivities of the two biomarkers were significantly higher than that of LBC and HPV16/18 genotyping (P<0.05). The three-year cumulative risks of CIN2+ were 69.0%, 48.4%, 34.8% and 50.0% for p16/Ki-67, p16/mcm, LBC and HPV16/18 genotyping. Women who tested positive on both p16/Ki-67 and p16/mcm2 at baseline had the highest RR value (39.64 [95% CI: 9.78-160.72]) of progressing to CIN2+ when compared to those who were negative for both. To conclude, p16/Ki-67 and p16/mcm2 dual staining can enhance the sensitivity of cytology in a single round of screening, and they can be predictors of high grade cervical lesions in the following years.

A cocktail of p16INK4a and Ki-67, p16INK4a and minichromosome maintenance protein 2 as triage tests for human papillomavirus primary cervical cancer screening.

Most human papillomavirus (HPV) infections are transient and additional triage approaches should be built after HPV-based primary cervical cancer screening. We evaluated the accuracy of p16/Ki-67 and p16/mcm2 dual staining as biomarkers for triaging HPV positive women in China. 4070 participants aged 35 to 64 years attending ongoing cervical cancer screening were enrolled in 2015-2016. Cervical exfoliated cells were collected for HPV DNA analysis and the residual positive specimens were tested for liquid-based cytology and biomarkers. Women infected with HPV 16/18 type or other 12 high-risk HPV types with abnormal cytology results received colposcopy. We found the positive rates of both biomarkers increased significantly with histology severity. p16/Ki-67 positivity in HPV16/18 group, other 12 high-risk HPV group and HPV negative group was 50.0%, 33.7% and 8.9%, respectively. The corresponding p16/mcm2 positivity was 70.0%, 56.3% and 6.7%, respectively. The sensitivity and specificity of p16/Ki-67 for CIN2+ in all HPV-positive women were 91.7% and 63.5%, with a referral rate of 36.2%, while p16/mcm2 were 87.5% and 42.1%, with a referral rate of 58.4%, respectively. The sensitivity of p16/Ki-67 increased to 95.8% for CIN2+ and 100% for CIN3+ when combined with high-grade cytology, without decrease in specificity. Our studies suggest that p16/Ki-67 is an efficient triaging biomarker for HPV-positive women and could reduce colposcopy workload. p16/mcm2 is more sensitive compared with cytology for identifying cervical lesions.

An evaluation of clinical performance of FTA cards for HPV 16/18 detection using cobas 4800 HPV Test compared to dry swab and liquid medium.

BACKGROUNDS: Effective dry storage and transport media as an alternative to conventional liquid-based medium would facilitate the accessibility of women in the low-resource settings to human papillomavirus (HPV)- based cervical cancer screening. OBJECTIVE: To evaluate analytical and clinical performance of indicating FTA™ Elute Cartridge (FTA card) for the detection of HPV16/18 and cervical precancerous lesions and cancer compared to dry swab and liquid medium. STUDY DESIGN: Ninety patients with abnormal cytology and/or HPV infection were included for analysis. Three specimens of cervical exfoliated cells from each woman were randomly collected by FTA card, dry swab or liquid-based medium prior to colposcopy examination. The subsequent HPV DNA tests were performed on cobas 4800 HPV platform. RESULTS AND CONCLUSIONS: High-risk HPV (hrHPV) positivity rate was 63.3%, 62.2% and 65.6% for samples collected by FTA card, dry swab and liquid medium, respectively. The overall agreements and kappa values for the detection of hrHPV, HPV 16 and HPV 18 between FTA card and liquid-based medium were 88.9% (κ=0.76), 97.8% (κ=0.94) and 100% (κ=1.0),respectively; between FTA card and dry swab were 92.1% (κ=0.83), 94.5% (κ=0.87) and 100% (κ=1.0), respectively. The performances of hrHPV tested by FTA card, dry swab, and liquid-based medium for detecting CIN2+ were comparable in terms of the sensitivity and specificity. The specificity of detection of CIN2+ by HPV16/18 increased by approximately 40% compared to hrHPV for any medium albeit at cost of a moderate loss of sensitivity. Dry medium might offer an alternative to conventional liquid-based medium in the HPV-based cervical cancer screening program especially in low-resource settings but still needs further evaluation.

Stability Study of Cervical Specimens Collected by Swab and Stored Dry Followed by Human Papillomavirus DNA Detection Using the cobas 4800 Test.

Safer, more convenient methods for cervical sample collection and storage are necessary to facilitate human papillomavirus (HPV) DNA testing in low-resource settings. Our study aimed to evaluate the stability of cervical specimens collected with dry swabs and stored dry, compared to liquid-based cytology (LBC) samples, as detected by HPV DNA testing. Women with abnormal cytological findings or HPV-positive results at colposcopy were recruited from the West China Second University Hospital, Sichuan University, between October 2013 and March 2014. From each woman, physicians collected cervical specimens with a swab placed into a Sarstedt tube and a CytoBrush placed into LBC medium. Samples were randomly assigned to be stored at uncontrolled ambient temperature for 2, 7, 14, or 28 days and then were tested for 14 high-risk HPV (HR-HPV) types using the cobas HPV test. The rates of agreement between dry swab and LBC samples for any HR-HPV type, HPV16, HPV18, and the 12 pooled HR-HPV types were 93.8%, 97.8%, 99.4%, and 93.2%, respectively, with kappa values of 0.87 (95% confidence interval [CI], 0.83 to 0.91), 0.94 (95% CI, 0.91 to 0.97), 0.94 (95% CI, 0.87 to 1.00), and 0.86 (95% CI, 0.82 to 0.90). The performance of swab samples for detection of cervical precancerous lesions by means of cobas HPV testing was equal to that of LBC samples, even with stratification by storage time. Dry storage of swab-collected cervical samples can last for 1 month without loss of test performance by cobas HPV testing, compared to LBC samples, which may offer a simple inexpensive approach for cervical cancer screening in low-resource settings.

p16 Immunohistochemistry Interpretation by Nonpathologists as an Accurate Method for Diagnosing Cervical Precancer and Cancer.

OBJECTIVE: We conducted a pilot study of whether nonpathologists could accurately diagnose cervical precancer in biopsies using only a basic light microscope, evaluating p16 immunohistochemistry (p16 IHC) of biopsies, and video-based training for both. MATERIALS AND METHODS: Using biopsies collected as part of a screening study conducted in rural China, we randomly selected 50 biopsies with a precancerous diagnosis of cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+) and 50 biopsies with diagnosis of CIN less severe than CIN2, and stained them for p16 using a commercial IHC kit. Twelve nonpathologists of varying educational backgrounds living in Beijing, China received video training and were assigned one of 4 sets of 25 CIN2+ and 25 CIN less severe than CIN2 for evaluation. A pathologist reviewed all 100 cases. RESULTS: The mean sensitivity and specificity of the p16 IHC staining scored by the nonpathologists were 91.7% and 94.1%, respectively, compared to scoring by the pathologist. The readers and the pathologist agreed on p16 IHC scoring for 42 (84%) of the 50 slides of CIN less severe than CIN2 and 37 (74%) of the 50 CIN2+ slides. The mean sensitivity and specificity for consensus CIN2+ of p16 IHC as scored by the readers were 88% and 87%, respectively, versus an overall sensitivity and specificity by the pathologist of 96% and 92%, respectively. CONCLUSIONS: We demonstrated that nonpathologists can accurately diagnose CIN2+ using p16 IHC alone.

p16INK4A immunohistochemical staining and predictive value for progression of cervical intraepithelial neoplasia grade 1: a prospective study in China.

p16(INK4A) is strongly expressed in tissues diagnosed as cervical intraepithelial neoplasia (CIN) and cancer in women infected with human papillomavirus (HPV), but few prospective studies have evaluated p16(INK4A) as a marker for the risk of low-grade CIN (CIN1) progression. We investigated the prevalence of p16(INK4A) immunostaining by CIN grade and whether overexpression of p16(INK4A) in CIN1 predicts future risk for high-grade CIN in Chinese women. 6,557 Chinese women aged 30-49 years were screened from 2003 to 2005 using cytology and carcinogenic HPV test. Colposcopy was performed on women with any abnormal result. p16(INK4A) Immunostaining was performed on biopsies from all women with CIN1, as well as randomly selected women with normal or CIN grade 2 and worse (CIN2+) biopsies. Women with CIN1 were followed up without treatment. Colposcopy was performed on all untreated women at a 2-year interval. The prevalence of p16(INK4A) staining was 2.7%, 42.7%, 75.5%, 79.6% and 100% among women with normal, CIN1, 2, 3 and cancer biopsies, respectively (p < 0.001). HPV positivity was strongly associated with p16(INK4A) staining [odds ratios (OR) = 12.8; 95% confidence intervals (CI): 5.2-31.6]. p16(INK4A) staining of CIN1 biopsies at baseline was associated with an increased risk of finding high-grade CIN over 2 years of follow-up (OR = 1.43; 95% CI: 0.52-3.91). The two-year cumulative incidence of CIN2+ for p16(INK4A) positive women was higher at 10.71% than for p16(INK4A) negative women at 1.30% (crude RR = 8.25, 95% CI: 1.02-66.62). p16(INK4A) overexpression is strongly associated with grade of CIN and risk of progression to high-grade CIN in women with low-grade lesions.

Focused ultrasound therapy for vulvar intraepithelial neoplasia in a mice model.

BACKGROUND: The purpose of this study was to determine the effectiveness and safety of focused ultrasound (FU) for the treatment of vulvar intraepithelial neoplasia (VIN) in a mice model. METHODS: Estradiol benzoate was subcutaneously injected into the abdomens of eighty 129/J mice. VIN was successfully induced in 56 mice and was divided into the FU group and the control group. Pathologic features and changes in vascular endothelial growth factor expression in the lesions were analyzed before and after treatment. RESULTS: Two months after treatment, lesions in 25 of the 56 mice showed restoration of normal skin. Nineteen of the 21 VINI and VINII lesions returned to normal and the other 2 VINII lesions were down graded to VINI, yielding a curative rate of 90.1%. In the control group, all 21 mice had persistent VIN (P < 0.0001). In the 14 mice with VINIII lesions, 6 returned to normal skin histology representing a curative rate of 42.9%, 5 were reclassified as VINI and 3 were reclassified as VINII. Thus, the total effectiveness rate was 100%. CONCLUSIONS: The present study suggests that FU therapy is effective, noninvasive and safe in treating VIN in a mice model.

[Clinical evaluation of the xMAP technology in detection of high-risk human papillomavirus].

OBJECTIVE: To evaluate the clinical application value of flexible multi-analyte profiling (xMAP) technology in detecting high-risk human papillomavirus (HR-HPV). METHODS: Totally 1 061 women, aged 21-65 years, were randomly enrolled into the study. Cervical exfoliated cells were used in xMAP technology and hybrid capture II (hc2). Pathological diagnosis was used as golden standard. Consistency of these two methods was assessed. RESULTS: The sensitivity and specificity of xMAP technology were 80.31% and 85.83%, respectively. The positive and negative predictive values were 44.5% and 96.9%, respectively. The Kappa value for consistency between xMAP technology and hc2 was 0.58. CONCLUSIONS: The specificity of xMAP technology is similar to hc2 test, but the sensitivity is inferior to hc2. However, these two methods show good consistency in the detection of HR-HPV.