Cervix Research Articles

Usefulness of the human papillomavirus DNA chip test as a complementary method for cervical cytology.

As a convenient and economical method of screening cervical cancer and precancerous pathologies, the Papanicolaou smear (Pap smear) has been most widely used. Nevertheless, it requires cytological changes for making diagnoses and reportedly has a high false-negative rate. In this study, the usefulness of the human papillomavirus (HPV) DNA chip test as a complementary method that can compensate for the defect of the Pap smear was investigated. Of the 6516 patients who simultaneously underwent a Pap smear and an HPV DNA chip test at Chonnam National University Hospital between January 2015 and December 2016, 1897, an initial PAP smear-negative patients who had undergone an additional Pap smear during their 2-year follow-up period were selected for this study. Of the subject patients, 281 underwent a cervical biopsy. The Pap smear follow-up of an initial Pap smear-negative subjects showed 53 (75.7%) HPV high-risk positive cases in the cytology low-grade lesion group (70 cases) and 46 (97.8%) HPV high-risk positive cases in the cytology high-grade lesion group (47 cases). The 281 biopsy cases included 67 biopsy low-grade lesion cases and 74 biopsy high-grade lesion cases, of which there were 45 (67.2%) and 67 (90.5%) HPV high-risk positive cases, respectively. The follow-up cytology on the high-risk HPV-positive subjects showed that the ratio of their high-grade lesions was 260.8 times greater than that of the high-risk HPV-negative subjects (OR = 260.8 and 95% CI: 36.1 and 1886.1); and their biopsy showed that the ratio of their high-grade lesions was 102.7 times greater than that of the HPV-negative subjects (OR = 102.7 and 95% CI: 14.0 and 753.3). The complementary use of the HPV DNA chip test may be useful in increasing the accuracy of screening examinations for the early diagnosis of uterine cervix cancer when combined with the Pap smear.

Laparoscopic versus open radical hysterectomy in FIGO 2018 early-stage cervical adenocarcinoma: Long-term survival outcomes after propensity score matching.

To compare the long-term survival outcomes of laparoscopic radical hysterectomy (LRH) and open radical hysterectomy (ORH) in International Federation of Gynecology and Obstetrics (FIGO) 2018 early-stage cervical adenocarcinoma. Based on the clinical diagnosis and treatment for cervical cancer in mainland China (Four C) database, the medical records of 1098 patients with FIGO 2018 early-stage cervical adenocarcinoma were retrospectively reviewed. Long-term and short-term survival outcomes of the two groups were compared using a multivariate Cox regression model and the log-rank method in the whole study population and after propensity score matching. There was no difference in disease-free survival (hazard ratio [HR] 0.921, 95% confidence interval [CI]: 0.532-1.595, p = 0.770) and overall survival (HR 1.168, 95% CI: 0.526-2.592, p = 0.702) between LRH (n = 468) and ORH (n = 468) in the risk-adjusted analysis. LRH resulted in significantly lower estimated blood loss (342.7 vs. 157.5 mL, p < 0.001) and shorter postoperative anal exhaust time (2.8 vs. 2.5 days, p < 0.001) in risk-adjusted analysis. The overall rates of intraoperative complications (2.4% vs. 4.3%, p = 0.100) and postoperative complications (7.5% vs. 6.2%, p = 0.437) showed no significant difference between the two groups. However, the LRH group had a significantly higher incidence of ureter injury (0.4% vs. 2.4%, p = 0.012) and great vessel injury (0.0% vs. 0.9%, p = 0.045) compared to the other group. No statistical variation in the site of recurrence was observed between the two groups (p = 0.613). LRH has comparable survival outcomes with ORH and was associated with earlier recovery in FIGO 2018 early-stage adenocarcinoma of the uterine cervix. However, the LRH group had higher risk of ureter injury and great vessel injury.

Paclitaxel-carboplatin plus bevacizumab therapy for advanced neuroendocrine carcinoma of the uterine cervix: A retrospective case series.

There is no conclusive data on the prognosis of patients who receive paclitaxel-carboplatin (TC) plus bevacizumab therapy for advanced neuroendocrine carcinoma (NEC) of the uterine cervix, a rare histological subtype of cervical cancer. Thus, the aim of this study was to determine the efficacy of TC chemotherapy plus bevacizumab and bevacizumab single maintenance therapy for advanced NEC of the cervix. This was a retrospective review of patients who received TC plus bevacizumab therapy for metastatic, recurrent, or persistent NEC of the cervix at seven institutions between 2015 and 2020. Relevant data were extracted from the patients' medical records and analyzed. Seven patients, including six with small-cell NEC and one with large-cell NEC, were included for analysis. Three patients received bevacizumab single maintenance therapy following TC plus bevacizumab therapy, whereas four patients did not receive bevacizumab single maintenance therapy. The median overall survival and progression-free survival of the patients who received bevacizumab single maintenance therapy were longer than those of the patients who did not receive the therapy (34 months vs. 10.5 months and 19 months vs. 5 months, respectively). However, the patients who received bevacizumab single maintenance therapy had received cisplatin-based chemotherapy previously. On the premise that cisplatin-based chemotherapy is administered as the first-line treatment for advanced NEC of the cervix, bevacizumab single maintenance therapy following TC plus bevacizumab may be considered the second- or third-line treatment. However, the risk of adverse events, such as intestinal perforation, should be discussed with patients.

Synchronous High-Grade Squamous Intraepithelial Lesion of the Fimbria of the Fallopian Tube in a 51-Year-Old Woman with Invasive Squamous Cell Carcinoma of the Uterine Cervix.

Primary squamous cell carcinoma or squamous intraepithelial lesion of the fallopian tube is a very rare finding with only a small number of cases worldwide. We describe the case of a 51-year-old woman, undergoing an abdominal hysterectomy after the diagnosis of an HPV-associated invasive squamous cell carcinoma of the uterine cervix with the unexpected detection of an HPV16-positive high-grade squamous intraepithelial lesion of the fimbria of the right fallopian tube in the resection specimen. The finding of an isolated, HPV-associated squamous intraepithelial lesion in the fallopian tube raises the question of a de novo development in this body compartment (after exclusion of a continuous metastatic spread from the uterine cervix) by taking a virus-associated field effect into account and should encourage the inclusion of this possibility when examining the fallopian tube in a routine setting.

Tubal cervical double ectopic pregnancy, missed diagnosis, and lessons from an extremely rare case with a systematic review of literature

ABSTRACT A very rare form of heterotopic pregnancy where one of the ectopic gestational sacs is located in the fallopian tube and the other in the cervix uteri is being presented. Unlike the only other similar case reported, where tubal ectopic was managed with salpingectomy and the cervical ectopic was diagnosed after the salpingectomy, our case was that of missed diagnosis of tubal ectopic while focusing on medical management of the cervical ectopic pregnancy. Management options for such situation are being discussed, and a review on the management of CEP is presented with a focus on conservative medical therapy. Conservative treatment in case of tubal cervical double ectopic may be feasible with early diagnosis after ruling out adverse parameters.

Cancer Statistics in Pakistan From 1994 to 2021: Data From Cancer Registry.

Pakistan has been systematically collecting cancer data since 1994 through cancer registries. This article presents a comprehensive analysis of cancer statistics in Pakistan from 1994 to 2021, including incidence and patterns. The total number of patients with malignant neoplasm was 111,941, and the number of patients registered was 109,863. Most patients were from Punjab (67.6%) and Khyber Pakhtunkhwa (20.2%). Breast cancer (22.2%), colorectum cancer (5.6%), leukemia (5.3%), lip and oral cavity cancer, and non-Hodgkin lymphoma (5.1%) were the top five prevalent cancers in all age groups and sexes. Breast (24.2%), colorectum (6.2%), lip and oral cavity (5.8%), non-Hodgkin lymphoma (4.4%), and prostate cancers (4.0%) were most common in adults in both sexes. In both sexes, the most common cancers among children were Hodgkin lymphoma (20.1%), acute lymphoblastic leukemia (19.8%), non-Hodgkin lymphoma (11.6%), osteosarcoma (7.0%), and retinoblastoma (6.2%). Breast (45.9%), ovary and uterine adnexa (4.9%), lip and oral cavity (4.2%), cervix uteri (4.0%), and colorectum cancers (3.9%) were most common in adult females. In adult males, colorectum cancer (8.7%), prostate cancer (8.5%), lip and oral cavity cancer (7.6%), non-Hodgkin lymphoma (6.4%), and liver and intrahepatic bile duct cancers were the top five most common malignancies. It has been found that breast cancer, colorectum cancer, prostate cancer, leukemia, and bone cancer rates are among the highest in Pakistan. This information may be useful in assessing the effectiveness of future intervention strategies.

Morphology, Histology, and Cytology of the Testis and Accessory Glands of Bolua turkiyae (Orthoptera, Tettigoniidae)

There are many morphological and histological studies in the world to investigate the structure of the external and internal organs of insects. These studies not only serve to illuminate the biology of insect species, but also to reveal taxonomic relationships. For this purpose, the detailed structure of the testis and accessory glands that are the main organs of the male reproductive system of Bolua turkiyae Ünal, 1999 (Orthoptera: Tettigoniidae) was searched with a light microscope, scanning electron microscope, and transmission electron microscope techniques in 2019-2020 in Gazi University, Prof. Dr. Zekiye Suludere Electron Microscope Center in this study. B. turkiyae is an endemic species distributed around Bolu province in Turkey. The reproductive system of male B. turkiyae is comprised of testis, vas deferens, and accessory glands. When the cross-sections of the oval and yellow testis were examined, it was observed that they contain many follicles. There are cysts in these follicles that have the developmental stages of the sperm. From the distal ends of the follicles to the proximal ends, the germarium, growth zone, maturation zone, and transformation zone are located respectively. In these stages, spermatogonium, spermatocyte, spermatids, and finally spermatozoa are formed. Accessory glands are hollow tubular structures of two different sizes and diameters. Single-layered cubic or pyramidal cells surround the lumen in both groups of accessory glands. It is hoped that these new data will contribute to our understanding of the structure of the male reproductive system of B. turkiyae.

Successful pregnancy in a female with embryonal rhabdomyosarcoma of the cervix who received biopsy and chemotherapy alone without recurrence after 16 years: a case report and literature review

BackgroundEmbryonal rhabdomyosarcoma (ERMS) of the uterine cervix is rare, but the population affected is mostly underage females. The scope of surgery has now evolved from extensive to limited, and organ-preserving surgery combined with chemotherapy is recommended to preserve the patient’s fertility. However, reports of birth outcomes are rare.CaseA minor woman with cervical ERMS who underwent only an outpatient biopsy of the lesion had no residual lesion on subsequent multipoint cervical biopsy and refused radical surgery or cervical conization, after which the patient received a nonclassical regimen of chemotherapy. The patient stopped the chemotherapy on her own, but the patient conceived spontaneously 16 years later with a good pregnancy outcome and no recurrence.ConclusionsThis case suggests that preservation of reproductive function is often feasible in immature women with cervical ERMS, and the prognosis is usually good as long as the primary tumour can be surgically removed and the lesion is free of residual disease. We also look forward to reports of subsequent growth and pregnancy outcomes in other children with reproductive tract RMS. In cervical ERMS, accurate evaluation of the disease and development of an individualized treatment plan are crucial, and the protection of reproductive function and psychological well-being deserves special attention.

The role of neoadjuvant chemotherapy in patients with high-grade neuroendocrine carcinoma of the uterine cervix (1313)

The role of neoadjuvant chemotherapy in patients with high-grade neuroendocrine carcinoma of the uterine cervix (1313)

The clinical impact of gastric-type among adenocarcinoma of the uterine cervix: A multi-center, retrospective study (1311)

The clinical impact of gastric-type among adenocarcinoma of the uterine cervix: A multi-center, retrospective study (1311)

Clear cell carcinoma of the uterine cervix; an unusual HPV-independent tumor: Clinicopathological features, PD-L1 expression, and mismatch repair protein deficiency status of 16 cases.

Endocervical clear cell carcinoma (c-CCC) is a rare and HPV-independent adenocarcinoma type of cervix. Being usually resistant to conventional chemotherapy. Immunotherapy has recently been added as a preferred regimen as a second-line treatment option for programed cell death-ligand 1 (PD-L1)-positive or mismatch repair (MMR) deficient cervical carcinomas. In this study, clinicopathological features, PD-L1 expression, and MMR deficiency status of c-CCCs were investigated. Sixteen c-CCC diagnosed cases were included in this study. PD-L1 expression was evaluated using two different PD-L1 clones (22C3 and SP263). MMR deficiency status of the cases was evaluated using four MMR proteins (MLH1, PMS2, MSH2, and MSH6). Most of the c-CCC cases were presented as FIGO Stage I (68.75%). PD-L1 expression in either tumoral or tumor-infiltrating immune cells (TILs) was present in 62.5% (10/16) and 69% (11/16) of the 22C3 and SP263 clones, respectively. Most of the cases with high TIL density were also positive for PD-L1. The PD-L1 expression rate was less than 50% in most of the cases and 12.5% of the cases shared extensive PD-L1 staining. Overall, MMR deficiency was observed in 31.25% of the cases. Most of the MMR-deficient cases (80%) were PD-L1 positive. Although our study cohort is limited, we have shown that PD-L1 expression and MMR deficiency can be found in c-CCCs in variable degrees. These findings suggest that accompanying TIL density and MMR deficiency could be used as candidates for predicting PD-L1 positivity for c-CCCs. However, to indicate the clinical importance of these findings, objective treatment outcomes of cases treated with immunotherapy should be seen.

Does Absence of Transformation Zone Component in Anal Cytology Sample Affects Detection of Squamous Intraepithelial Lesions?

Does Absence of Transformation Zone Component in Anal Cytology Sample Affects Detection of Squamous Intraepithelial Lesions?

The impact of transformation zone representation on the frequency of abnormal cervical cytological results

ObjectiveTo compare the frequency of abnormal cervical cytological results with and without representation of the transformation zone (TZ) in a medium-sized city in Brazil according to the Bethesda categorization. MethodsWe performed an analytical observational study evaluating cytological results over 15 years from conventional smears collected within the Public Brazilian Health System in Araçatuba, Brazil. Tests were stratified by age and cytological result according to Brazilian guidelines and the Bethesda System. ResultsThere were 261,881 examinations, 159,251 with and 102,630 without TZ representation. The global frequency of abnormal results was higher in smears with TZ representation (crude odds ratio [OR] 4.03; 95% confidence interval [CI] [3.71–4.38]). Considering only women between 25 and 64 years (the target of the national guidelines), there were higher results for high-grade squamous intraepithelial lesions (OR 11.54; 95% CI 6.74–19.78), low-grade squamous intraepithelial lesions (OR 2.82; 95% CI 2.17–3.67) atypical squamous cell in which high-grade intraepithelial lesion cannot be excluded (OR 6.90; 95% CI 4.91–9.66) and atypical squamous cell of undetermined significance (OR 3.53; 95% CI 3.11–4.01) among cases with TZ representation. ConclusionSamples with TZ representation were associated with higher rates of abnormal results. Health professionals should be regularly trained to understand the weakness of cytological examinations when the TZ is not represented, especially in developing countries.

Cancer incidence estimates in adults aged 60 years and older living in low-and-middle-income countries for the years 2020 and 2040.

Previous studies have shown a disproportionate rise in cancer incidence in low-and-middle-income countries (LMICs) due to rapid population ageing. This study aims to describe the cancer incidence in adults aged 60 years and older in LMICs to inform cancer control planning. Using the latest GLOBOCAN estimates for 2020, we describe the cancer incidence and the top five cancer sites among adults aged 60 years and older living in LMICs. We also project the incidence in 2040 by applying population projections, assuming no changes in incidence rates and risk profiles over time. In 2020, 6.3 million new cancer cases were diagnosed in older adults in LMICs, constituting over half of the global incidence burden (55%). In females aged 60 years and older living in LMICs, breast, lung, colon, stomach, and cervix uteri were the most frequent cancer types representing 51% of the total number of new cancer cases in older females. In males aged 60 years and older living in LMICs, lung, prostate, stomach, liver and colon were the most frequent cancer types representing 58% of the total number of new cancer cases in this subgroup. Variations were observed between income categories. The number of new cancer diagnoses in adults aged 60 years and older living in LMICs will almost double by 2040, reaching 11.5 million new cancer cases. The greatest increase is expected to happen in lower-income countries (+158% in lower-middle-income countries (excluding India) and +99% in low-income countries versus +38% in upper-middle-income countries). In conclusion, our findings call for an urgent adaptation of healthcare systems in LMICs by developing geriatric oncology and by including older adults in research, clinical guidelines, insurance schemes and cancer prevention policies.

European consensus statement on expert colposcopy

BackgroundFollowing the publication of the European consensus statement on standards for essential colposcopy in 2020, the need for standards relating to more complex and challenging colposcopy practice was recognised. These standards relate to colposcopy undertaken in patients identified through cervical screening and tertiary referrals from colposcopists who undertake standard colposcopy only.This set of recommendations provides a review of the current literature and agreement on care for recognised complex cases. With good uptake of human papillomavirus (HPV) immunisation, we anticipate a marked reduction in cervical disease over the next decade. Still, the expert colposcopist will continue to be vital in managing complex cases, including previous cervical intraepithelial neoplasia (CIN)/complex screening histories and multi-zonal disease. AimsTo provide expert guidance on complex colposcopy cases through published evidence and expert consensus. Material & methodsMembers of the EFC and ESGO formed a working group to identify topics considered to be the remit of the expert rather than the standard colposcopy service. These were presented at the EFC satellite meeting, Helsinki 2021, for broader discussion and finalisation of the topics. Results & discussionThe agreed standards included colposcopy in pregnancy and post-menopause, investigation and management of glandular abnormalities, persistent high-risk HPV+ with normal/low-grade cytology, colposcopy management of type 3 transformation zones (TZ), high-grade cytology and normal colposcopy, colposcopy adjuncts, follow-up after treatment with CIN next to TZ margins and follow-up after treatment with CIN with persistent HPV+, and more. These standards are under review to create a final paper of consensus standards for dissemination to all EFC and ESGO members.

A comprehensive analysis of GATA3 expression in carcinomas of various origins with emphasis on lung carcinomas.

GATA3 is a transcription factor involved in the embryogenesis of multiple human tissues and organs and in maintaining cell differentiation and tissue homeostasis in the adult organism. GATA3 is also involved in carcinogenesis and is regarded as a sensitive marker for urothelial and breast carcinomas, although its expression in carcinomas of non-breast/urothelial origin has been frequently reported. In this study, we sought to examine the extent and intensity of GATA3 expression in various carcinomas, mainly lung, urothelial, breast, and various other primary sites. Patients with breast carcinoma (n=40), carcinoma of the urinary bladder/renal pelvis (n=40), lung carcinoma (n=110), and various other origins (n=45) were included in the study. 165 patients had a primary tumor diagnosis, and 70 cases had a metastatic tumor diagnosis. Our results showed that GATA3 expression was significantly more common in carcinomas of the breast, urinary bladder, and renal pelvis compared to all other origins. All primary and 93% of metastatic urinary bladder carcinomas and 94% of primary and 80% of metastatic breast carcinomas expressed GATA3. Expression was lower in the non-urothelial histology of urinary primaries and in triple-negative breast carcinomas (TNBC). Focal staining, mostly faint, was seen in 5.6% of the primary lung adenocarcinomas and 35% of the primary lung squamous cell carcinomas. More extensive and intense staining was seen in 3.7% of the primary lung adenocarcinomas and 12% of the primary lung squamous cell carcinomas. Expression, mostly focal, was also seen in 30% of the metastatic lung carcinomas. Finally, high expression was seen in 12.5% of the other tumors (one metastatic pancreatic carcinoma, one metastatic salivary gland adenocarcinoma not otherwise specified, one metastatic squamous cell carcinoma of the skin, one primary uterine cervix serous carcinoma, and one squamous cell carcinoma of the head and neck), and focal expression was present in another 22% of them. No ideal cut-off for positivity for GATA3 staining could be identified, as increasing the cut-off in either the extent or the intensity of staining increased specificity but decreased sensitivity. In conclusion, our study shows that although GATA3 staining is very helpful in everyday practice in determining the breast/urothelial origin of carcinomas, there are two caveats to its use: the first is that nonclassical histologies of urothelial carcinomas and TNBC may be negative for the marker, and secondly, carcinomas of various origins may show (although rarely) intense positivity.

Strengthening mechanism and plasticity deformation of crystalline/amorphous Cu3Fe/Fe3Cu nanolayered composite

Metallic glasses possess high strength and excellent elastic properties due to their amorphous atomic structure. However, they often display brittleness and suffer catastrophic failure because of shear localization, without exhibiting significant macroscopic plastic deformation under tension. In this paper, an effective method to enhance the strength and ductility of metallic glasses is presented by molecular dynamics simulation. The approach involves controlling the thickness of the crystalline Cu3Fe and amorphous Fe3Cu layers. The results indicate that increasing the thickness of the crystal layer improves the strength of the nanolayered composite. The crystalline/amorphous interface impedes stress propagation in the shear transformation zone, thereby enhancing the yield stress of the composite. Additionally, the presence of Hirth dislocations in the crystal layer strengthens the composite. The generation and annihilation of fixed dislocations in the crystal layer cause stress fluctuations in the composite, which further enhances its ductility. However, a small content of crystalline layer can cause stress concentration towards the shear band, leading to rapid fracture failure and reduced ductility. These findings shed light on the plastic deformation behavior of crystalline/amorphous composites at the nanoscale, providing valuable theoretical guidance for designing high-strength and ductile metallic materials.

Extensive lesions and a positive cone margin are strong predictors of residual disease in subsequent hysterectomy following conization for squamous intraepithelial lesion grade 2 or 3 study design

BackgroundThis study aimed to determine the predictive factors for post-conization of residual disease in subsequent hysterectomy for cervical intraepithelial neoplasia grade 2 or 3.MethodsThis retrospective study included 267 patients with histologically confirmed cervical intraepithelial neoplasia grade 2 or 3 who underwent hysterectomy within 7 months after conization. Clinical data (e.g., age, menopausal status, gravidity, parity, type of transformation zone, conization method) as well as pathological data pertaining to conization and hysterectomy were collected from medical records. A logistic regression model was used to analyze the relationship between the variables and risk of residual lesions in hysterectomy samples.ResultsOverall, 70 (26.2%) patients had residual lesions in their hysterectomy specimens. Univariate analyses revealed that age ≥ 50 years (p=0.019), endocervical gland involvement(p=0.013), positive margin(p < 0.001), and involvement of 3–4 quadrants(p < 0.001) were risk factors for residual lesions. Conversely, postmenopausal status, gravidity ≥ 3, parity ≥ 2, loop electrosurgical excision procedure, and type III transformation zone were not risk factors for residual lesions. A positive margin(p < 0.001) and multiple-quadrant involvement(p < 0.001) were identified as independent risk factors for residual lesions on multivariate analysis.ConclusionsMultiple-quadrant involvement and a positive cone margin were reliable predictive factors for residual disease. Total hysterectomy or repeated cervical conization should be considered for patients with these two risk factors. The identification of high-risk patients with extensive lesions by colposcopic examination before conization is indispensable, as it will enable surgeons to perform conization with consideration of risk factors and possibly improve the approach used for the excisional procedure. For high-risk patients, colposcope-guided cold-knife conization is preferred when resources permit.

Potential diagnostic value of quantitative superb microvascular imaging in premalignant and malignant cervical lesions.

The purpose of this study was to assess the diagnostic efficacy of the vascular index (VI) on superb microvascular imaging (SMI) in distinguishing normal uterine cervical epithelium, high-grade cervical intraepithelial neoplasia (CIN), and cervical cancer. The retrospective study included women with pathology-confirmed CIN or cervical cancer, who underwent transvaginal ultrasound and SMI between April 2021 and October 2022. The SIM manifestations of normal cervix and cervical lesions were reviewed. SIM were measured and converted into vascular index (VI) which compared between cervical lesions and control groups. We have retrospectively compared ultrasound features of cervical lesions and characteristics of patients. Measurement reliability was evaluated by intra class correlation coefficient (ICC). A total of 235 consecutive females were enrolled, comprising 38 with high-grade CIN, 96 with cervical cancer, and 101 with a normal uterine cervix. The microvascular architecture exhibited significant variations between premalignant and malignant cervical lesions. Branch-like patterns were predominantly observed in high-grade CIN, while crab claw-like and fireball-like patterns were more commonly associated with cervical cancer. The median VI of cervical cancer (34.7 ± 10.3) was significantly higher than that of high-grade CIN (17.6 ± 4.2) (P < 0.001). Moreover, the VI values of cervical cancer differed significantly among different FIGO stages and pathological types (P < 0.001 and P = 0.003, respectively). The VI demonstrated superior diagnostic performance for cervical lesions compared to vascular patterns (AUC = 0.974 and 0.969, respectively). Using a cut-off value of 25.5, the VI yielded a sensitivity of 82.3% and a specificity of 99.3% for cervical lesion detection. The SMI parameter (VI) exhibited a significantly higher value in cervical cancer compared to high-grade CIN, with a high level of agreement among observers. These findings suggest that quantitative SMI holds promise as an imaging technique for the detection and characterization of cervical lesions.

A multi-functional hypoxia/esterase dual stimulus responsive and hyaluronic acid-based nanomicelle for targeting delivery of chloroethylnitrosouea

Carmustine (BCNU), a vital type of chloroethylnitrosourea (CENU), inhibits tumor cells growth by inducing DNA damage at O6 position of guanine and eventually forming dG-dC interstrand cross-links (ICLs). However, the clinical application of BCNU is hindered to some extent by the absence of tumor selectivity, poor stability and O6-alkylguanine-DNA alkyltransferase (AGT) mediated drug resistance. In recent years, tumor microenvironment has been widely utilized for advanced drug delivery. In the light of the features of tumor microenvironment, we constructed a multifunctional hypoxia/esterase-degradable nanomicelle with AGT inhibitory activity named HACB NPs for tumor-targeting BCNU delivery and tumor sensitization. HACB NPs was self-assembled from hyaluronic acid azobenzene AGT inhibitor conjugates, in which O6-BG analog acted as an AGT inhibitor, azobenzene acted as a hypoxia-responsive linker and carboxylate ester bond acted as both an esterase-sensitive switch and a connector with hyaluronic acid (HA). The obtained HACB NPs possessed good stability, favorable biosafety and hypoxia/esterase-responsive drug-releasing ability. BCNU-loaded HACB/BCNU NPs exhibited superior cytotoxicity and apoptosis-inducing ability toward the human uterine cervix carcinoma HeLa cells compared with traditional combined medication of BCNU plus O6-BG. In vivo studies further demonstrated that after a selective accumulation in the tumor site, the micelles could respond to hypoxic tumor tissue for rapid drug release to an effective therapeutic dosage. Thus, this multifunctional stimulus-responsive nanocarrier could be a new promising strategy to enhance the anticancer efficacy and reduce the side effects of BCNU and other CENUs.