Objective: To investigate the natural regression and related factors of high-grade squamous intraepithelial lesion (HSIL) in the cervix of childbearing age women, and to evaluate the applicability of conservative management for future fertility needs. Methods: This study included 275 patients of reproductive age with fertility needs, who were diagnosed as HSIL by biopsy from April 30, 2015 to April 30, 2022, including 229 cases (83.3%) cervical intraepithelial neoplasia (CIN) Ⅱ and 46 cases (16.7%) CIN Ⅱ-Ⅲ. They were followed-up without immediate surgery in the First Affiliated Hospital of Nanjing Medical University. The median follow-up time was 12 months (range: 3-66 months). The regression, persistence and progression of lesions in patients with HSIL were analyzed during the follow-up period, the influencing factors related to regression and the time of regression were analyzed. Results: (1) Of the 275 HSIL patients, 213 cases (77.5%, 213/275) experienced regression of the lesion during the follow-up period. In 229 CIN Ⅱ patients, 180 cases (78.6%) regressed, 21 cases (9.2%) persisted, and 28 cases (12.2%) progressed. In 46 CIN Ⅱ-Ⅲ patients, 33 cases (71.7%) regressed, 12 cases (26.1%) persisted, and 1 case (2.2%) progressed to invasive squamous cell carcinoma stage Ⅰ a1. There was no significant difference in the regression rate between the two groups (χ²=1.03, P=0.309). (2) The average age at diagnosis, age <25 years old at diagnosis were independent influencing factor of HSIL regression in univariate analysis (all P<0.05). There was no significant difference between HSIL regression and pathological grading, the severity of screening results, human papillomavirus (HPV) genotype, colposcopy image characteristics, number of biopsies during follow-up and pregnancy experience (all P>0.05). (3) The median regression times for patients aged ≥25 years and <25 years at diagnosis were 15 and 12 months, respectively. Kaplan-Meier analysis showed that age ≥25 years at diagnosis significantly increased the median regression time compared to <25 years (χ²=6.02, P=0.014). Conclusions: For HSIL patients of childbearing age, conservative management without immediate surgical intervention is preferred if CINⅡ is fully evaluated through colposcopy examination. Age ≥25 years at diagnosis is a risk factor affecting the prognosis of HSIL patients.
Pregnancy ; Humans ; Female ; Adult ; Cervix Uteri/pathology* ; Uterine Cervical Neoplasms/pathology* ; Uterine Cervical Dysplasia/pathology* ; Biopsy ; Colposcopy/methods* ; Squamous Intraepithelial Lesions/pathology* ; Carcinoma in Situ/pathology* ; Papillomaviridae/genetics* ; Papillomavirus Infections/diagnosis* ; Squamous Intraepithelial Lesions of the Cervix/pathology*

Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) Ⅰ and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINⅡ and more lesions after treatment with CINⅡ or CIN Ⅲ (CINⅡ/CIN Ⅲ). All participants were randomly divided into the test group and the control group at a ratio of 2∶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ²=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ²=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.
Female ; Humans ; Adult ; Middle Aged ; Cervix Uteri/pathology* ; Uterine Cervical Neoplasms/pathology* ; Papillomavirus Infections/diagnosis* ; Cell Wall Skeleton ; Persistent Infection ; Powders ; Uterine Cervical Dysplasia/pathology* ; Immunotherapy ; Papillomaviridae

Adenocarcinoma, Clear Cell ; diagnosis ; etiology ; therapy ; Cervix Uteri ; pathology ; Child ; Diethylstilbestrol ; Fatal Outcome ; Female ; Humans ; Magnetic Resonance Imaging ; Pregnancy ; Prenatal Exposure Delayed Effects ; Uterine Cervical Neoplasms ; diagnosis ; etiology ; therapy

Charcoal can be used for preoperative localization of metastatic lymph nodes in the neck. Charcoal remains stable without causing foreign body reactions during as hort period. However, foreign body reactions may develop if charcoal is left in situ for more than 6 months. We reported a case of charcoal granuloma mimicking local recurrence on fluorodeoxyglucose-positron emission tomography/computed tomography and ultrasonography in a 47-year-old woman who had cervical lymph node dissection due to metastatic invasive ductal carcinoma of the breast.
Breast Neoplasms/pathology/surgery/therapy ; Carcinoma/*pathology/surgery/therapy ; Cervix Uteri/pathology/ultrasonography ; Charcoal/toxicity ; Female ; Fluorodeoxyglucose F18/diagnostic use ; Granuloma/*diagnosis/pathology ; Humans ; Lymph Nodes/*surgery/ultrasonography ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Recurrence, Local ; Positron-Emission Tomography ; Radiopharmaceuticals/diagnostic use ; Tomography, X-Ray Computed

Adenocarcinoma ; metabolism ; pathology ; Adenocarcinoma, Clear Cell ; metabolism ; pathology ; Adult ; Carcinoma, Endometrioid ; metabolism ; pathology ; Cervix Uteri ; metabolism ; pathology ; surgery ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Diagnosis, Differential ; Electrosurgery ; Endometrial Neoplasms ; metabolism ; pathology ; Female ; Humans ; Hyperplasia ; Keratin-7 ; metabolism ; Mesonephros ; metabolism ; pathology ; surgery ; Neprilysin ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; pathology

OBJECTIVETo investigate the clinical application of diffusion weighted imaging (DWI) in uterine cervical cancer and the apparent diffusion coefficient (ADC) value in diagnosis and predicting treatment response.

METHODSTwenty-eight patients with advanced primary cervical cancer confirmed by pathology and 10 cases of normal uterine cervix as control were recruited in this prospective clinical trial. To analyze the correlation between tumor volume measured in DWI and tumor maximum diameter measured according to the RECIST criteria. To compare the ADC value differences among the uterine cervical cancer, uterine myometrium, and normal uterine cervix. To compare the ADC values in 17 cancer patients before and after treatment.

RESULTSThe illustration of tumor boundary in DWI was superior to conventional T2WI and post-enhancement T1WI. The DWI with higher b value (2000 s/mm(2)) had a better signal-to-noise ratio. The tumor volume measured in DWI has good correlation with tumor maximum diameter according to RECIST criteria (r = 0.759, P < 0.01). When b = 800 s/mm(2), the ADC values of the uterine cervical cancer, uterine myometrium, and normal uterine cervix were (9.85 ± 1.55)×10(-3) mm(2)/s, (14.20 ± 2.80)×10(-3) mm(2)/s, and (14.14 ± 0.45) ×10(-3) mm(2)/s. When b = 2000 s/mm(2), the ADC values of the uterine cervical cancer, uterine myometrium and normal uterine cervix were (7.38 ± 0.98)×10(-3) mm(2)/s, (8.52 ± 2.38)×10(-3) mm(2)/s, and (8.60 ± 0.63)×10(-3) mm(2)/s, respectively. There were significant differences between the cervical cancer and normal cervix or uterine myometrium (P < 0.001 for both). When b = 800 s/mm(2), the ADC value was (9.85 ± 1.55)×110(-3) mm(2)/s before and (13.41 ± 2.93)×10(-3) mm(2)/s after treatment (P < 0.001). When b = 2000 s/mm(2), the ADC value was (7.38 ± 0.98)×10(-3) mm(2)/s before and (8.93 ± 1.92)×10(-3) mm(2)/s after treatment (P = 0.008). Univariate logistic regression analysis showed that 25% ADC, 50%ADC, and 75%ADC in the tumor ADC value histogram before treatment were significantly correlated to the treatment outcome of cervical cancer (P < 0.05 for all). Multivariate regression analysis showed that 25%ADC, 50%ADC, and 75%ADC in the tumor ADC value histogram before treatment were not significantly correlated to the treatment outcome of cervical cancer (P > 0.05 for all). The values of ROC curves were 25%ADC = 0.818, 50%ADC = 0.775, and 75%ADC = 0.716 (P > 0.05), however, the 25% ADC showed a relatively stronger statistical power.

CONCLUSIONSDWI helps to confirm the morphology and exact target zone of the tumor for radiotherapy. DWI volume measurement is well correlated with RECIST criteria, particularly in volume measurement of irregular tumors. ADC value has a potential in quantitatively monitoring treatment response and predicting outcome of cervical cancers.

Adenocarcinoma ; diagnosis ; drug therapy ; pathology ; radiotherapy ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Squamous Cell ; diagnosis ; drug therapy ; pathology ; radiotherapy ; Case-Control Studies ; Cervix Uteri ; pathology ; Cisplatin ; therapeutic use ; Diffusion Magnetic Resonance Imaging ; Female ; Humans ; Middle Aged ; Myometrium ; pathology ; Prospective Studies ; ROC Curve ; Radiotherapy, Conformal ; Treatment Outcome ; Tumor Burden ; Uterine Cervical Neoplasms ; diagnosis ; drug therapy ; pathology ; radiotherapy

Adenocarcinoma ; genetics ; pathology ; virology ; Carcinoma in Situ ; genetics ; pathology ; virology ; Cervical Intraepithelial Neoplasia ; genetics ; pathology ; virology ; Cervix Uteri ; pathology ; virology ; Cytological Techniques ; DNA, Viral ; analysis ; Female ; Follow-Up Studies ; Humans ; Neoplasm Grading ; Papillomaviridae ; genetics ; isolation & purification ; Papillomavirus Infections ; diagnosis ; Uterine Cervical Neoplasms ; genetics ; pathology ; virology

Quantitative real-time RT-PCR (RT-qPCR) is being widely used in microRNA expression research. However, few reports detailed a robust identification and validation strategy for suitable reference genes for normalisation in microRNA RT-qPCR studies. The aim of this study was to identify the most stable reference gene(s) for quantification of microRNA expression analysis in uterine cervical tissues. A microarray was performed on 6 pairs of uterine cervical tissues to identify the candidate reference genes. The stability of candidate reference genes was assessed by RT-qPCR in 23 pairs of uterine cervical tissues. The identified most stable reference genes were further validated in other cohort of 108 clinical uterine cervical samples: (HR-HPV- normal, n = 21; HR-HPV+ normal, n = 19; cervical intraepithelial neoplasia [CIN], n = 47; cancer, n = 21), and the effects of normalizers on the relative quantity of target miR-424 were assessed. In the array experiment, miR-26a, miR-23a, miR-200c, let-7a, and miR-1979 were identified as candidate reference genes for subsequent validation. MiR-23a was identified as the most reliable reference gene followed by miR-191. The use of miR-23a and miR-191 to normalize expression data enabled detection of a significant deregulation of miR-424 between normal, CIN and cancer tissue. Our results suggested that miR-23a and miR-191 are the optimal reference microRNAs that can be used for normalization in profiling studies of cervical tissues; miR-23a is a novel microRNA normalizer.
Cervical Intraepithelial Neoplasia/diagnosis/genetics/*metabolism/pathology ; Cervix Uteri/*metabolism/pathology ; Early Detection of Cancer ; Female ; Gene Expression Profiling/*standards ; Humans ; MicroRNAs/genetics/*metabolism/standards ; Microarray Analysis ; Reference Standards ; Reverse Transcriptase Polymerase Chain Reaction ; Uterine Cervical Neoplasms/diagnosis/genetics/*metabolism/pathology

Adult ; Cervix Uteri ; pathology ; Female ; Humans ; Sarcoma, Alveolar Soft Part ; diagnosis ; Uterine Cervical Neoplasms ; diagnosis

Adult ; Alkaline Phosphatase ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cervix Uteri ; metabolism ; pathology ; surgery ; Choriocarcinoma ; metabolism ; pathology ; Chorionic Gonadotropin ; metabolism ; Diagnosis, Differential ; Female ; GPI-Linked Proteins ; metabolism ; Humans ; Hysterectomy ; Placental Lactogen ; metabolism ; Pregnancy ; Trophoblastic Tumor, Placental Site ; metabolism ; pathology ; surgery ; Uterine Cervical Neoplasms ; metabolism ; pathology ; surgery