Feasibility study of focused ultrasound in the treatment of vulvar low-grade squamous intraepithelial lesions with persistent symptoms.

OBJECTIVE: This study aimed to investigate the feasibility, efficacy, and safety of focused ultrasound (FUS) for the treatment of vulvar low-grade squamous intraepithelial lesions (VLSIL) with persistent symptoms. METHODS: This retrospective analysis included 24 VLSIL patients who underwent FUS treatment. At each follow-up visit, the clinical response was assessed including changes in symptoms and signs. In addition, the histological response was assessed based on the vulvar biopsy results of the 3rd follow-up. Clinical and histological response were assessed to elucidate the efficacy. RESULTS: A total of 22 patients completed follow-up and post-treatment pathological biopsies. After treatment, the clinical scores of itching decreased from 2.55 ± 0.51 to 0.77 ± 0.81 (p < 0.05). Furthermore, the clinical response rate and histological response rate were 86.4% and 81.8%, respectively. Only two cured patients indicated recurrence in the 3rd and 4th year during the follow-up period and achieved cure after re-treatment. In terms of adverse effects, only one patient developed ulcers after treatment, which healed after symptomatic anti-inflammatory treatment without scarring, and no other treatment complications were found in any patients. None of the patients developed a malignant transformation during the follow-up period. CONCLUSION: This study revealed that FUS is feasible, effective, and safe for treating VLSIL patients with persistent symptoms, providing a new solution for the noninvasive treatment of symptomatic VLSIL.

Clinical and epidemiological features of high-risk human papillomavirus infection in patients with cervical intraepithelial lesions.

OBJECTIVE: In this study, we analyzed the clinical and epidemiological features of high-risk human papillomavirus (HR-HPV) infection in patients with cervical intraepithelial lesions. METHODS: Retrospective analysis was performed on the clinical data of 240 cases of histologically confirmed cervical squamous intraepithelial lesions to determine any correlation between HPV infection characteristics, age distribution, and cervical epithelial lesions. RESULTS: Patients between the ages of 31 and 40 with cervical intraepithelial lesions were more likely to have high-grade squamous intraepithelial lesions (HSIL; 40.7%) than low-grade squamous intraepithelial lesions (LSIL; 31.3%) (P < 0.05). In patients with HSIL, HR-HPV16, HR-HPV33, and HR-HPV52 were the most common types of HPV infection, while in patients with LSIL, HR-HPV16, HR-HPV52, and HR-HPV58 were the most common types of HPV infection. The highest percentage of single infections occurred in the HSIL group (69.6%), followed by the LSIL group (68.8%). HSIL was present in a significant number of patients (28.6%) aged 30 years and above who tested positive for 12 HPV types but negative for TCT. CONCLUSION: The prevalence of HSIL is greatest in younger patients. Patients with cervical epithelial lesions typically have a single infection of a high-risk HPV genotype-HR-HPV16, HR-HPV33, HR-HPV52, or HR-HPV58. Patients aged 30 years and above who test positive for one of 12 types of HPV but negative for TCT are at increased risk for developing HSIL. In order to detect cervical lesions early and begin treatment without delay, colposcopy should be performed regardless of whether or not a high-risk HPV infection is present.

Effects of 5-aminolevulinic acid photodynamic therapy for cervical low-grade squamous intraepithelial lesions with HR-HPV infections.

Objective: To determine the effectiveness and safety of 5-aminolevulinic acid mediated photodynamic therapy (5-ALA PDT) in HR-HPV infected patients with cervical low-grade squamous intraepithelial lesions (LSIL) and to explore possible factors affecting treatment outcomes. Methods: This retrospective study included 96 patients with histologically confirmed cervical LSIL and high-risk human papillomavirus (HR-HPV) infection. They received 5-ALA PDT treatment once a week for a total of 3 courses. All patients were evaluated by cytology tests, HPV DNA assay, colposcopy, and biopsy at 2 weeks, 3 months, and 6 months checkpoint. The chi-square test were used to evaluate the differences in various clinical data, and a p value <0.05 was considered statistically significant. Results: At 2 weeks, 3 months, and 6 months checkpoint, colposcopies showed that the cervical iodine-unstained area under VILI (visual inspection with Lugol's iodine) significantly reduced (p < 0.01) with no structure changes. At 3 months and 6 months checkpoint, the pathological regression rate reached 87.5% (84/96) and 94.79% (91/96), while the HR-HPV clearance rates reached 80.21% (77/96) and 93.75% (90/96) respectively. We also examined the efficacy in the HPV 16/18-related group and non-HPV 16/18-related group. The HR-HPV clearance rate in the HPV16/18 group [94.87% (37/39)] was significantly higher than that of the non-HPV 16/18 group [70.17% (40/57)]. However, at 6 months after treatment, the clearance rate of the HPV 16/18 group [94.87% (37/39)] showed no statistical difference from the non-HPV 16/18 group [92.30% (53/57)]. Conclusion: Topical 5-ALA PDT can effectively eliminate HR-HPV infection and treat low-grade cervical squamous intraepithelial lesions, it offers an alternative treatment option for patients with LSIL, especially for those with fertility requirements and who wish to preserve cervical structure or function.

Classification of Vascular Hotspots and Micro-Vessel Flow Velocity Waveforms in Low-Grade Squamous Intraepithelial Lesions and HPV Condyloma of the Cervix.

To assess hotspot micro-vessel flow velocity waveforms in human papillomavirus (HPV) cervical infections using transvaginal power Doppler ultrasound (TV-PDU) and to explore the associations of these sonographic parameters with HPV condyloma and low-grade squamous intraepithelial lesions (LSIL) of the cervix. A total of 39 patients with cervical HPV infections with abnormal cytology and colposcopy results (26 cases of LSIL; 13 cases of HPV condyloma) were enrolled to assess the vascular classification of the cervix and micro-vessel flow velocity using TV-PDU before treatment; 40 individuals with a pathologically normal cervix were used as the control group; seven parameters were measured, including vascular grading classification (Class I, Class II, and Class III), lowest pulsatility index (PI), resistance index (RI), peak systolic velocity (PS), end-diastolic velocity (ED), time average maximum velocity (TAMV), and the vascular index (VI = PS/ED). According to vascular classification, most LSILs were class I (69.2%, 18/26), followed by class II (26.9%, 7/26) and class III (3.8%, 1/26). Most HPV condylomas were class I (92.3%, 12/13), and one was class II (7.7%, 1/13). PI, RI, VI (p < 0.0001), and the PSs (p < 0.05) were significantly lower in these cases than in the controls. The ED and TAMV were not significantly different between the patients and controls (p = 0.4985 and p = 0.1564). No sonographic parameter was significantly different between LSIL and HPV condyloma. The mean PI, RI, and VI were significantly lower in LSIL than in the controls. For HPV condyloma, a PI of 1.07 had an 84.6% sensitivity, 85.0% specificity, and an AUC of 88.8%; for LSIL, a PI of 1.08 had a 100% sensitivity, 85% specificity, and an AUC of 94.2%; for HPV infection (HPV condyloma + LSIL), a PI of 1.08 had a 94.9% sensitivity, 85% specificity, and an AUC of 92.4%. Hotspot vascular classification and micro-vessel flow velocity waveforms may provide a potential practical method for the auxiliary diagnosis of cervical HPV infection. The PI may represent a valuable index for distinguishing the micro-vessel flow velocity waveforms in LSIL and HPV condyloma. Since the case numbers were limited in the current study, further validation is needed.

Prediction value with a novel and accurate tissue-based human papillomavirus detection method in low-grade squamous intraepithelial lesions.

BACKGROUND: The progression rate from CIN1 to CIN3 is 9.0% and that for invasive cancer is 1.0%. The large majority of CIN1 lesions regress spontaneously, and the treatment of CIN1 is still controversial. AIMS: The aim of this study is to investigate the responsible HPV genotype in the low-grade SILs, then to predict the presence of high-grade SILs, and determine whether further treatment is needed. METHODS: We use the methods of manual microdissection with FFPE tissue specimens and the E6/E7 uniplex polymerase chain reaction (PCR) to detect HPV in the lesions. RESULTS: The HPV test was performed on 72 biopsy tissue specimens, and 55 (76.4%, 55/72) of them were HPV positive. Nine (16.4%, 9/55) of them escalated to CIN2 after LEEP or cervical conization, and 46 (83.6%, 46/55) were still CIN1. There were 17 (23.6%, 17/72) cases with HPV-negative results in cervical biopsy tissues. HPV test of cervical biopsy diagnosed with CIN1 has a positive predictive value of 16.4% in the presence of CIN2 or higher lesions, a negative predictive value of 94.1%, a specificity of 25.8%, and a sensitivity of 90.0%. HPV test of cervical biopsy tissues for the prediction of HPV infection in LEEP or cone surgery tissues had a positive predictive value of 80.0%, a negative predictive value of 82.3%, a specificity of 56.0%, and a sensitivity of 93.6%. CONCLUSIONS: It is the first time that we have detected HPV genotype in the low-grade SILs by the methods of manual microdissection with FFPE tissue specimens and the E6/E7 uniplex PCR. Patients with cervical biopsy tissue diagnosed with CIN1 and with a negative or only low-risk HPV type result can be considered for follow-up. Conversely, in cases of cervical biopsy tissue diagnosed with CIN1 positive for high-risk HPV, surgery or a close follow-up program can be selected.

Hispanic Ethnicity and Cervical Cancer Precursors Among Low-Income Women in Arizona.

PURPOSE: In the United States, Hispanics are more likely to be diagnosed with cervical cancer compared to Non-Hispanic Whites. Annually, 250,000 to 1 million women are diagnosed with a precursor to CC. The aim of this study was to assess whether Hispanics have a higher prevalence of cervical dysplasia compared to Non-Hispanics Whites among a population of low-income women. PATIENTS AND METHODS: We analyzed the results of 10,911 cervical cytology tests administered between 2003 and 2016 that were funded through the Center for Disease Control and Prevention's (CDC) program for low-income, uninsured women entitled the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). In the state of Arizona, the program is called the Well Women HealthCheck Program (WWHP). Logistic regression was used to identify increased risk of dysplasia, including low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL/ICC), and multinomial logistic regression was used to assess increased likelihood for LSIL and HSIL/ICC as separate categories. RESULTS: In the crude analysis, Hispanic ethnicity was modestly associated with higher prevalence of LSIL (odds ratio (OR)=1.39, 95% CI=1.01-1.91), but this association was not statistically significant after adjusting for confounders. However, in the final models, lower income was independently associated with LSIL (adjusted odds ratio [aOR]=1.55, 95% CI=1.30-1.44), while smoking (aOR=2.88, 95% CI=1.21-6.84) and no history of Pap test within five years (aOR=3.54, 95% CI=1.61-6.99) were independently associated with HSIL. CONCLUSION: After adjusting for confounding in a sample of low-income women with comparable Pap screening rates, ethnicity was not associated with greater prevalence of abnormal pap smears. However, other variables were independently associated with LSIL and HSIL. The higher proportion of LSIL cases among lower income individuals compared to those with higher incomes, and the higher proportion of HSIL cases observed among those screened least regularly stresses the importance of programs like WWHP: programs that target low-income, uninsured women. These programs help save lives.

High-sensitivity C-reactive Protein and Regression of Low-grade Squamous Intraepithelial Lesion: The Role of Low-grade Inflammation in Cervical Carcinogenesis.

BACKGROUND: Inflammation is emerging as a potential mechanism of cervical carcinogenesis. However, few studies have investigated the association between host inflammatory status and the natural course of cervical precursor lesion. The aim of this study was to assess the probability of LSIL regression, associated with an inflammatory biomarker, high-sensitivity C-reactive protein (hs-CRP). METHODS: In a longitudinal cohort study, female participants were examined annually or biannually using cervical cytology between 2006 and 2015. Incident LSIL cases were included in the analysis, with regression defined as at least one consecutive normal cytologic result. A total of 520 women aged 22-64 years were followed up for LSIL regression. The multivariable-adjusted hazard ratios (HRs) for LSIL regression were estimated using a parametric proportional hazards model. RESULTS: During 827.5 person-years of follow-up, 486 out of 520 subjects (93.5%) showed LSIL regression. After adjusting several important potential confounders, a higher quartile of hs-CRP levels was significantly associated with a lower rate of regression (for quartile 4 vs quartile 1, inverse HR 1.33; 95% CI, 1.04-1.69; P for trend = 0.028). CONCLUSIONS: The low rate of spontaneous regression recorded in women with higher hs-CRP lends support to the role of the perturbated host inflammatory status in cervical carcinogenesis, and suggests that hs-CRP level could help monitor LSIL.

The effect of local photodynamic therapy with 5-aminolevulinic acid for the treatment of cervical low-grade squamous intraepithelial lesions with high-risk HPV infection: A retrospective study.

BACKGROUND: High-risk HPV infection is the main cause of cervical cancer and pre-cancerous lesions. The current principle of clinical management of cervical low-grade squamous intraepithelial lesion is observation for 2 years. Progression to high-grade squamous intraepithelial lesion warrants intervention. Primary treatment option is surgical excision which may have a negative impact on fertility. Topical photodynamic therapy is a non-invasive and targeted therapy. We investigated the clinical efficacy of this therapy for cervical low-grade squamous intraepithelial lesion with high-risk HPV infection. METHODS: A retrospective study consisting of 258 female patients aged 21-69 years with a histologically confirmed cervical low-grade squamous intraepithelial lesion with high-risk HPV infection was carried out. Subjects were treated with three sessions of 20 % 5-aminolevulinic acid photodynamic therapy at intervals of 7-14 days. Three months after treatment, the effect was evaluated through HPV typing, Thinprep cytology and colposcopy directed biopsy. Six months after treatment, the photodynamic therapy effect was evaluated by HPV genotyping and Thinprep cytology first, the pathological examination would be performed at the 6-month follow-up point if the cytological results indicated the risk of high-grade squamous intraepithelial lesions. RESULTS: Three months after treatment, among 258 low-grade squamous intraepithelial lesion with high-risk HPV infection patients, total baseline HPV remission rates was 64.34 % (166/258). The remission rate of HPV16/18 group was not statistically significant compared to the HPV non-16/18 group (73.13 % vs 61.26 %, p = 0.081).The remission rates of the <50 age group was significantly higher than the >50 age group (67.28 %vs46.34 %, p = 0.001). The total lesion regression rate wa treatment, among 258 low-grade squamous intraepithelial lesion with high-risk HPV infection patients, total baseline HPV remission rates was 64.34 % (166/258). The remission rate of HPV16/18 group was not statistically significant compared to the HPV non-16/18 group (73.13 % vs 61.26 %, p = 0.081).The remission rates of the <50 age group was significantly higher than the >50 age group (67.28 %vs46.34 %, p = 0.001). The total lesion regression rate was 84.88 % (219/258). 12.8 % (33/258) of patients did not progress. Only 2.33 % (6/258) patients progressed to high-grade squamous intraepithelial lesion and accepted loop electrosurgical excision procedure. The patients >50 age group had significant higher progression rate than the patients ＜50 age group (p＜0.05). Six months after treatment, except for 6 patients who progressed to high-grade squamous intraepithelial lesion and underwent surgical treatment, the total baseline HPV remission rates was up to 82.54 % (208/252). CONCLUSION: 5-aminolevulinic acid photodynamic therapy was highly effective and did not appear to create cervical damage.. It might be an ideal treatment for cervical low-grade squamous intraepithelial lesion with high-risk HPV infection, but this requires additional clinical trials.

Triage of low-grade squamous intraepithelial lesions using human papillomavirus messenger ribonucleic acid tests-A prospective population-based register study.

INTRODUCTION: The optimal clinical management of women diagnosed with low-grade squamous intraepithelial lesions (LSIL) during cervical cancer screening remains unclear. In this prospective cohort study, we compared the clinical performance of two human papillomavirus (HPV) mRNA tests for triage of women with LSIL in Denmark. MATERIAL AND METHODS: In a nationwide pathology register, we identified women aged 23-65 years with LSIL during 2008-2012. We included women tested for HPV mRNA with the PreTect HPV Proofer test for five high-risk HPV types (n = 2176) or the Aptima assay for 14 high-risk HPV types (n = 426). Subsequent histological diagnoses of cervical intraepithelial neoplasia grades 2, 3 or cancer (CIN2+) were identified in the register. We calculated the sensitivity and specificity for CIN2+ at 18 and 36 months of follow up, and the cumulative incidence of CIN2+ among women testing positive and negative, overall and by age (23-29, 30-39, 40-65 years). RESULTS: The proportion of women with a positive mRNA test at baseline was higher in women tested with Aptima (66.7%) than in women tested with Proofer (42.8%). After 18 months, Aptima had higher sensitivity for CIN2+ than Proofer (98% [95% CI 94% to 100%] vs 85% [95% CI 82% to 88%]), whereas Proofer showed higher specificity than Aptima (67% [95% CI 64% to 70%]) vs (40% [95% CI 33% to 46%]). Aptima had particularly low specificity in women aged <40 years (23-29: 19% [95% CI 5% to 36%]; 30-39: 10% [95% CI 0% to 33%]). The 36-month cumulative incidence of CIN2+ was higher in Proofer positive (54.3% [95% CI 50.9% to 57.8%]) than in Aptima positive women (37.6% [95% CI 31.2% to 44.8%]). In women with a negative mRNA test, the 36-month cumulative incidences of CIN2+ were 13.1% (95% CI 10.8% to 15.8%) and 5.9% (95% CI 1.7% to 19.0%) for Proofer and Aptima, respectively. CONCLUSIONS: In women with LSIL, Aptima had high sensitivity for CIN2+, but low specificity, especially in women aged <40 years. The Proofer test may be useful to limit immediate colposcopy referrals in younger women with LSIL, but given its low sensitivity and negative predictive value, Proofer negative women must be followed with repeat cytology.

Persistence rate of cervical human papillomavirus infections and abnormal cytology in Rwanda.

OBJECTIVES: In this study, we determined the incidence and persistence of human papillomavirus (HPV) strains and of squamous intraepithelial lesions (SIL) or worse cytology in 237 HIV-positive and HIV-negative Rwandan women and whether the interleukin (IL)-28B single nucleotide polymorphism (SNP) at rs12979860 correlated with susceptibility to and persistence of HPV infection. METHODS: Cervical samples were collected at baseline and after 9, 18 and 24 months for a 40-HPV DNA screening test and a ThinPrep Pap test. Genotyping of the IL-28B SNP rs12979860 was performed using real-time polymerase chain reaction (PCR). RESULTS: Chronic high-risk (HR) HPV infections occurred in 56% of HIV-positive women, while no HIV-negative women developed HPV chronicity. High-grade SIL (HSIL) or cancer was diagnosed in 38% of HIV-positive women with persistent HR-HPV infections. HIV and HR-HPV positivity at baseline were factors associated with an increased risk of HPV persistence. Additionally, HR-HPV positivity at baseline was associated with an increased risk of developing HSIL or worse cytology. The unfavourable T/x genotype at rs12979860 is common among Africans, and women with this genotype were found to be more commonly infected with HPV. CONCLUSIONS: HPV screening in Rwanda may help to identify women at risk of developing cervical cancer and polymorphism in IL-28B may be associated with risk of contracting  HPV infection.

Risk detection for high-grade cervical disease using Onclarity HPV extended genotyping in women, ≥21 years of age, with ASC-US or LSIL cytology.

OBJECTIVES: There is growing interest in using human papillomavirus (HPV) genotyping as a risk-based triage approach for women with atypical squamous cells-undetermined significance (ASC-US) and low-grade squamous intraepithelial lesions (LSIL) cytology. METHODS: This analysis includes 2807 subjects with ASC-US or LSIL cytology, ≥21 years, from the baseline phase of the Onclarity HPV trial. All women were referred to colposcopy/biopsy. Hierarchical-ranked prevalence and risk values, associated with high-grade cervical disease, were calculated based on extended genotyping. RESULTS: HPV 16 carried the highest risk for cervical intraepithelial neoplasia grade 2 or worse (≥CIN2) in both the ASC-US and LSIL populations. Risk of ≥CIN3 and ≥CIN2 associated with the other 13 genotypes varied somewhat for women with ASC-US and LSIL, however, HPV 31, 18, 33/58, 51 and 52 appear to comprise an intermediate risk band. Risk associated with HPV 35/39/68, 45, and 56/59/66, in either cytology population, was relatively low and beneath the benchmark threshold risk for immediate colposcopy. Restricting the analysis to women 21-24 years, ≥25 years, or ≥30 years produced similar results. CONCLUSIONS: HPV genotyping identified multiple risk bands for ≥CIN3 and ≥CIN2 in the ≥21 year-old ASC-US and LSIL populations. These results support a 1-year follow-up period to preclude immediate colposcopy for ASC-US or LSIL women positive for the lowest-risk HPV genotypes.

Accuracy of genotyping for HPV16 and 18 to triage women with low-grade squamous intraepithelial lesions: a pooled analysis of VALGENT studies.

Background: Genotyping for the most carcinogenic human papillomavirus (HPV) types (HPV16/HPV18) can identify high risk of underlying cervical precancer and guide further management. Research design and methods: A pooled analysis was performed of the clinical accuracy of high-risk HPV (hrHPV) testing and HPV16/18 genotyping in triage of women with low-grade squamous intraepithelial lesions (LSIL). Data regarding 24 assays evaluated in four VALGENT validation panels were used. Results: In women with LSIL, hrHPV had a pooled sensitivity for CIN2+ of 95.5% (95% CI: 91.0-97.8%) and a specificity of 25.3% (95% CI: 22.2-28.6%). HPV16/18 genotyping had a sensitivity and specificity for CIN2+ of 52.9% (95% CI: 48.4-57.4%) and 83.5% (95% CI: 79.9-86.5%), respectively. The average risk of CIN2+ was 46.1% when HPV16/18-positive, 15.5% in women who were HPV16/18-negative but positive for other hrHPV types and 4.3% for hrHPV-negative women. Conclusions: Triage of women with LSIL with HPV16/18 genotyping increases the positive predictive value compared to hrHPV testing but at the expense of lower sensitivity. Arguably, women testing positive for HPV16/18 need further clinical work-up. Whether colposcopy referral or further surveillance is recommended for women with other hrHPV types may depend on the post-test risk of precancer and the local risk-based decision thresholds.

Clinical significance of human papillomavirus 16/18 E6 protein detection in shunting and prognosis of patients with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions / 肿瘤研究与临床

Objective To evaluate the value of human papillomavirus (HPV) 16/18 E6 protein detection in shunting and prognosis in patients with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL). Methods A total of 98 patients with ASCUS or LSIL from the Affiliated Cancer Hospital of Shanxi Medical University between May 2014 and May 2015 were selected as the subjects. All of them received the thin-cytologic test (TCT), HPV DNA, HPV16/18 E6 protein tests and colposcopy examination. After 3-year follow-up of patients with cervical intraepithelial neoplasia (CIN) grade Ⅰor bellow lesions diagnosed by biopsy and 30 negative controls, the above tests were performed again. The efficacies of all the tests were analyzed. The value of CIN grade Ⅱ or above was predicted. Results The sensitivity, specificity, positive predictive value and negative predictive value in predicting CIN grade Ⅱor above lesions of HPV16/18 E6 protein , HPV DNA and HPV16/18 DNA was 30.8％, 95.3％, 50.0％, 90.0％, respectively; 84.6％, 37.6％, 17.2％, 94.1％, respectively and 61.5％, 67.1％, 22.2％, 91.9％, respectively in shunting study. The relative risk (RR) of CIN grade Ⅱor above lesions in patients with positive HPV16/18 E6 protein, persistent positive HPV16/18 DNA and positive HPV16/18 DNA was 13.429, 10.231 and 8.343, respectively in the follow-up study. Odds ratio (OR) of HPV16/18 E6 positive protein presenting persistent positive HPV16/18 DNA was 34.833 (95％ CI 5.020-241.711). Conclusions In patients with ASCUS and LSIL, the specificity and positive predictive value of HPV16/18 E6 protein in predicting CIN grade Ⅱ or above lesions are higher than those of HPV DNA and HPV16/18 DNA. Moreover, these patients with HPV16/18 E6 protein positive have a higher risk of developing CIN grade Ⅱ or above lesions and persistent positive HPV16/18 DNA.

Clinical value of p16 and geminin in the progress of patients with low?grade squamous intraepithelial lesions / 中国综合临床

Objective To analyze the positive expression levels of p16 ( p16ink4a), cell cycle factor geminin and Ki-67 in low-grade squamous intraepithelial lesions ( LSIL),and to further explore the ability of these indicators to evaluate the progression of LSIL patients. Methods From January 2015 to June 2018,276 cervical specimens from Jiading District Central Hospital of Shanghai were retrospectively studied, and 148 LSIL patients were selected. According to the results of the second examination,LSIL patients were divided into three groups: (1) no lesion (natural regression) group 90 cases; (2) LSIL persistent group 38 cases; (3) high-grade Squamous Intraepithelial Lesion (HSIL) group 20 cases. Immunohistochemistry was performed on the first biopsy tissues and the relative positive ratios of p16, geminin and Ki-67 were calculated. Spearman correlation analysis identified the correlation between the above indicators and the progress of the disease; ROC curve was used to calculate the best diagnostic value of each indicator,and multivariate logistic regression analysis was included to explore the ability of the above indicators to assess the risk of patients progressing to HSIL. Results In the HSIL group, p16 ( 51. 26 ± 17. 15)%, geminin relative positive ratio ( 45. 92 ± 15. 70)% was higher than those in the LSIL group(( 43. 71 ± 11. 84)%, (21. 68± 14. 47)%) and regression group (( 17. 92 ± 9. 60)%, ( 0. 16 ± 0. 03)%) . The difference were statistically significant ( F＝2. 922, 2. 751, all P＜0. 05) . Spearman correlation analysis showed that the relative positive ratio of p16 ( r＝0. 27,P＝0. 014) and geminin ( r＝0. 44,P＜0. 001) presented a notable positive correlation with the progression of the disease. Under the ROC curve,the best diagnostic values of p16, geminin and Ki-67 were 38. 9%, 32. 5% and 18. 6%, respectively. Multivariate logistic regression analysis showed that the relative positive ratio of p16 was higher than 38. 9%(OR＝4. 366,P＝0. 006),and geminin was higher than 32. 5%( OR ＝ 5. 392, P ＝ 0. 011 ) had a higher risk of progression to HSIL. Conclusion p16 and geminin may be effective biomarkers for identifying patients with advanced LSIL.

Colposcopic biopsy findings among women with either HPV-16 only or HPV-18 only who have normal cervical cytology.

OBJECTIVE: To compare colposcopic biopsy results among women with normal cervical cytology who had positive test results for either HPV-16 only or HPV-18 only. METHODS: A cross-sectional study was conducted at Zekai Tahir Burak Women's Health Research and Training Hospital, Ankara, Turkey, between July 1, 2015, and October 31, 2017. Colposcopic biopsy results were compared among women in the HPV-16 only (n=185) and HPV-18 only (n=43) groups. RESULTS: Women who had HPV-16 only were more likely to be smokers than women with HPV-18 only (P=0.003). By contrast, women with HPV-18 only were more likely to be aged at least 45 years than women who had HPV-16 only (P=0.038). High-grade squamous intraepithelial lesions were detected more frequently in the HPV-16 only group (51 [27.6%]) than in the HPV-18 only group (4 [9.3%]; P=0.010). By contrast, no between-group difference was found for the rate of invasive cervical cancer, which was detected in 1 (0.5%) woman in the HPV-16 only group and 1 (2.3%) woman in HPV-18 only group (P=0.342). CONCLUSION: Although the risk of high-grade squamous intraepithelial lesions was increased among women with HPV-16 only, this finding did not influence the rate of invasive cervical cancer when compared with women in the HPV-18 only group.

Evolución de las lesiones escamosas intraepiteliales de bajo grado del cérvix (2012-2013) / Evolution of Cervix Low-Grade Squamous Intraepithelial Lesions (2012-2013)

Introducción: las lesiones intraepiteliales cervicales son precursoras del cáncer de cuello uterino, enfermedad que causó 465 muertes en Cuba en el año 2015. Objetivo: describir la evolución de las lesiones intraepiteliales de bajo grado del cérvix durante un bienio según lo dispuesto en el Programa Nacional de Diagnóstico Precoz del Cáncer Cervicouterino. Métodos: se realizó un estudio descriptivo, longitudinal y prospectivo a 79 pacientes diagnosticadas citológicamente con una lesión escamosa intraepitelial de bajo grado en el período comprendido entre el 1ro de septiembre de 2012 y el 31 de agosto de 2013 en el Hospital Materno Ramón González Coro. Seguimiento evolutivo cada seis meses durante dos años. Resultados: 54,4 por ciento tenía entre 25 y 39 años de edad. Del total, 65,8 por ciento negativizó la citología entre los 6 y 18 meses. En los dos años de evolución, 25,3 por ciento del total progresó a una lesión de alto grado. Existió buena correlación citocolposcópica en 80 por ciento de las pacientes. El cálculo de la mediana de la zona transformación atípica en las lesiones de alto grado fue de 25 por ciento, muy superior a las de bajo grado. Hubo confirmación histológica en todos los casos cuya lesión progresó. Conclusiones: las pacientes que negativizaron la citología lo hizo durante los 18 meses de seguimiento. Existió buena relación citohistológica, no así colpohistológica. La evolución no guardó relación con las variables sociodemográficas excepto con el uso de DIU. Lesiones que ocupan más del 20 por ciento de la zona de transformación se relacionó con progresión hacia una lesión escamosa intraepitelial de alto grado(AU)

Introduction: Cervical intraepithelial lesions are signs of cervical cancer, a disease that caused 465 deaths in Cuba in 2015. Objective: To describe the evolution of low-grade intraepithelial lesions of the cervix during a biennium according to the provisions of the National Program of Early Diagnosis of Cervical Cancer. Methods: A descriptive, longitudinal and prospective study was carried out on 79 patients diagnosed by cytology with a low-grade squamous intraepithelial lesion from September 1, 2012 to August 31, 2013 at Ramón González Coro Gyneco-Obstetric Hospital. These subjects received an evolutionary follow-up every six months for two years. Results: 54.4 percent were between 25 and 39 years of age; 65.8 percent had negative cytology between 6 and 18 months. In the two years of evolution, 25.3 percent of the total progressed to a high-grade lesion. There was good cytocolposcopic correlation in 80 percent of the patients. The calculation of the median of the atypical transformation zone in the high-grade lesions was 25 percent, much higher than the low-grade ones. There was histological confirmation in all cases whose lesion progressed. Conclusions: Negative cytology in our patients was assessed during the 18 months of follow-up period. There was good cytohistological relationship, but not so for colpohistological relationship. The evolution was not related to the sociodemographic variables except with the use of IUD. Lesions that occupy more than 20 percent of the transformation zone were associated with progression towards a high-grade squamous intraepithelial lesion(AU)

Evolución de las lesiones escamosas intraepiteliales de bajo grado del cérvix (2012-2013) / Evolution of Cervix Low-Grade Squamous Intraepithelial Lesions (2012-2013)

Introducción: las lesiones intraepiteliales cervicales son precursoras del cáncer de cuello uterino, enfermedad que causó 465 muertes en Cuba en el año 2015. Objetivo: describir la evolución de las lesiones intraepiteliales de bajo grado del cérvix durante un bienio según lo dispuesto en el Programa Nacional de Diagnóstico Precoz del Cáncer Cervicouterino. Métodos: se realizó un estudio descriptivo, longitudinal y prospectivo a 79 pacientes diagnosticadas citológicamente con una lesión escamosa intraepitelial de bajo grado en el período comprendido entre el 1ro de septiembre de 2012 y el 31 de agosto de 2013 en el Hospital Materno Ramón González Coro. Seguimiento evolutivo cada seis meses durante dos años. Resultados: 54,4 por ciento tenía entre 25 y 39 años de edad. Del total, 65,8 por ciento negativizó la citología entre los 6 y 18 meses. En los dos años de evolución, 25,3 por ciento del total progresó a una lesión de alto grado. Existió buena correlación citocolposcópica en 80 por ciento de las pacientes. El cálculo de la mediana de la zona transformación atípica en las lesiones de alto grado fue de 25 por ciento, muy superior a las de bajo grado. Hubo confirmación histológica en todos los casos cuya lesión progresó. Conclusiones: las pacientes que negativizaron la citología lo hizo durante los 18 meses de seguimiento. Existió buena relación citohistológica, no así colpohistológica. La evolución no guardó relación con las variables sociodemográficas excepto con el uso de DIU. Lesiones que ocupan más del 20 por ciento de la zona de transformación se relacionó con progresión hacia una lesión escamosa intraepitelial de alto grado(AU)

Introduction: Cervical intraepithelial lesions are signs of cervical cancer, a disease that caused 465 deaths in Cuba in 2015. Objective: To describe the evolution of low-grade intraepithelial lesions of the cervix during a biennium according to the provisions of the National Program of Early Diagnosis of Cervical Cancer. Methods: A descriptive, longitudinal and prospective study was carried out on 79 patients diagnosed by cytology with a low-grade squamous intraepithelial lesion from September 1, 2012 to August 31, 2013 at Ramón González Coro Gyneco-Obstetric Hospital. These subjects received an evolutionary follow-up every six months for two years. Results: 54.4 percent were between 25 and 39 years of age; 65.8 percent had negative cytology between 6 and 18 months. In the two years of evolution, 25.3 percent of the total progressed to a high-grade lesion. There was good cytocolposcopic correlation in 80 percent of the patients. The calculation of the median of the atypical transformation zone in the high-grade lesions was 25 percent, much higher than the low-grade ones. There was histological confirmation in all cases whose lesion progressed. Conclusions: Negative cytology in our patients was assessed during the 18 months of follow-up period. There was good cytohistological relationship, but not so for colpohistological relationship. The evolution was not related to the sociodemographic variables except with the use of IUD. Lesions that occupy more than 20 percent of the transformation zone were associated with progression towards a high-grade squamous intraepithelial lesion(AU)

Atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion triage in Korean women: Revisiting the 2012 American Society of Colposcopy and Cervical Pathology screening guidelines.

OBJECTIVE: To determine whether triage for atypical squamous cells of undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion (LSIL) from the updated American Society for Colposcopy and Cervical Pathology cervical cancer screening guidelines is applicable in Korean women. METHODS: We investigated women with ASC-US or LSIL including referred from local hospitals visited for cervical cancer screening at Korea University Guro Hospital from February 2004 to December 2014. Detailed information on the results of Papanicolaou (Pap) smears, human papillomavirus (HPV) DNA tests, and cervical biopsies were collected through chart review. Cervical biopsy results were compared in eligible women according to individual Pap smear findings and HPV DNA status. RESULTS: Of 216,723 possible cases, 3,196 were included. There were 212 (6.6%) women with ASC-US and 500 (15.6%) with LSIL. The risk of ≥cervical intraepithelial neoplasia (CIN) 2 was significantly higher in women who were ASC-US/HPV+ than ASC-US/HPV- and LSIL/HPV+ than LSIL/HPV- (93.3% vs. 6.7% and 96.7% vs. 3.3%, P<0.001 and P<0.001, respectively). The risk of ≥CIN 3 was also significantly higher in women who were ASC-US/HPV+ than ASC-US/HPV- and LSIL/HPV+ than LSIL/HPV- (97.0% vs. 3.0% and 93.0% vs. 7.0%, P<0.001 and P<0.001, respectively). Age-stratified analysis revealed that more CIN 2 or CIN 3 was diagnosed in women aged 30 to 70 with ASC-US or LSIL when HPV DNA was present. CONCLUSION: Observation with Pap and HPV DNA tests rather than immediate colposcopy is a reasonable strategy for ASC-US or LSIL when the HPV DNA test is negative, especially in women aged 30 to 70. Reflection of these results should be considered in future Korean screening guidelines.

Comparison of the diagnostic value of cervical cytology and HPV HR DNA testing for the diagnosis of low-grade and high-grade squamous intraepithelial lesions across different age groups.

OBJECTIVES: To assess the diagnostic value of cervical cytology and HPV HR DNA testing for the diagnosis of low grade and high-grade squamous intraepithelial lesions across different age groups. MATERIAL AND METHODS: The study included 1103 patients, age 25-70 years. All patients underwent in-depth diagnostic tests following either an abnormal Pap test result or a clinically suspicious cervical lesion. In all women the following examinations were performed: a molecular test detecting 14 high-risk types of HPV, a colposcopy examination, as well as directed-biopsy of the cervix. The studied population was subdivided into four age groups. RESULTS: It was observed that the percentage of high grade squamous intraepithelial lesions (HSIL) and cancers increased with women's age. Sensitivity of both methods for detecting high-grade squamous intraepithelial lesions was highest for women aged 40-49 years. Sensitivity values of HPV testing was higher than that of cervical cytology among women under age 50. CONCLUSIONS: Specificity of HPV testing increased significantly with age of women and was several fold higher across all age groups than the specificity of cervical cytology.

Relationship between low-grade squamous intraepithelial lesions and high risk human papillomavirus / 临床与实验病理学杂志

Purpose To study the infection mode and distribution of high risk human papillomavirus (HR-HPV) in lowgrade squamous intraepithelial lesions (LSILs) and to analysis its effect.Methods HPV genotype of 328 cervical tissues embedded by paraffin which contained 168 LSILs and 160 highgrade squamous intraepithelial lesions (HSILs) were detected by the methods of real-time fluorescence quantitative PCR and in situ hybridization.Results Diseased cells of LSIL stained with hematoxylin and eosin(HE) were concentrated in the upper layer of the cervical squamous epithelium,whereas HSIL were concentrated in the lower layer of the epithelium in HE staining.In LSIL,the positive ratcs of HR-HPV was 95.2％.In LSIL and HSIL,HPV 16/18 positive rates were 26.2％,57.5％,respectively.Other HR-HPV positive rates were 80.9％,55.0％,respectively.The differences were statistically significant (P ＜0.001).HR-HPV positive rate was 70.2％ in the group of in situ hybridization.The positive cells were confined to the surface and middle layer of the LSIL cervical squamous epithelium.Conclusion HR-HPV infection is closely related to LSIL,especially other HR-HPV (except for HPV 16/18).The infection mode of HR-HPV in LSIL starts from the surface layer of the cervical squamous epithelium.