High-Risk Human Papilloma Virus Genotype Distribution and Correlation with Cervical Cytomorphological Data in Turkish and Immigrant Women in Mersin Province.

Human papilloma virus (HPV) is the most common sexually transmitted viral agent in the world and the most common cause of cervical cancer. HPV prevalence and genotype distribution vary by region and demographic data. In a province in the south of Turkey that constantly receives immigration, we aimed to determine the prevalence of high-risk HPV (HR-HPV) genotypes, evaluate the compatibility between cervical Pap smear cytology results patients and HR-HPVs, and make an up-to-date contribution to the elucidation of epidemiological data. In this single-centre study, a total of 12,641 women aged 18 and over were evaluated retrospectively from January 2019 to July 2022. HPV detection and genotyping were analysed by the PCR method. Bethesda scoring was used for Pap smear cytological evaluation. The overall prevalence of HR-HPV was 12.6% (12.7% in Turkish women, 11.2% in foreign women). Among the typed HPVs that were detected, HPV-16 (31%) was found first, followed by HPV-18 (8%). The prevalence of HR-HPV was higher in women with abnormal cytology (977/1762, 55.4%) than in women with normal cytology (620/10879, 5.7%) (p<0.001). Turkey doesn't yet have a national HPV immunisation program. We think that determining the specific regional frequency of other HR-HPVs separately will be useful in the follow-up of the natural course of the type-specific infection and in vaccine studies in the future.

Laminin receptor 1 expression in premalignant and malignant squamous lesions of the cervix.

Laminin receptor 1 (LAMR) may have a role in the progression of premalignant squamous epithelial lesions to cervical cancer. Therefore, we aimed to investigate the expression of laminin receptor 1 (LAMR) in normal, premalignant, and malignant tissues of the uterine cervix. Paraffin blocks of 129 specimens with the diagnoses of normal cervical tissue (n = 33), cervical intraepithelial neoplasia (CIN) 1 (n = 30), CIN 2 (n = 14), CIN 3 (n = 28), and squamous cell carcinoma (n = 24) were immunohistochemically stained with LAMR antibody and its expression percentage, pattern, and intensity in these tissues were assessed. Compared to the other groups, the nonstaining with LAMR was highest in low grade squamous intraepithelial lesion (LSIL) (p < 0.0001). LAMR expression, which was positive in less than 50% of cells with weak staining, increased significantly between normal cervical epithelium and high-grade squamous intraepithelial lesion (HSIL) or invasive carcinoma, as well as between LSIL and HSIL (p < 0.0001). Between LSIL and invasive carcinoma, a significant increment was also observed for weak staining in less than 50% of cells (p < 0.001). LAMR expression, which was positive in more than 50% of cells with strong staining, was significantly higher in normal cervical tissue compared to the other groups (p < 0.0001). Disease progression related gradual increment of LAMR expression from normal cervical epithelium or LSIL towards HSIL or cervical cancer reveals that LAMR may play an important role in the transition from premalignant to malignant state in cervical lesions.

Tobacco Smoke Condensate Induces Morphologic Changes in Human Papillomavirus-Positive Cervical Epithelial Cells Consistent with Epithelial to Mesenchymal Transition (EMT) with Activation of Receptor Tyrosine Kinases and Regulation of TGFB.

High-risk human papillomavirus (HR-HPV; HPV-16) and cigarette smoking are associated with cervical cancer (CC); however, the underlying mechanism(s) remain unclear. Additionally, the carcinogenic components of tobacco have been found in the cervical mucus of women smokers. Here, we determined the effects of cigarette smoke condensate (CSC; 3R4F) on human ectocervical cells (HPV-16 Ect/E6E7) exposed to CSC at various concentrations (10-6-100 µg/mL). We found CSC (10-3 or 10 µg/mL)-induced proliferation, enhanced migration, and histologic and electron microscopic changes consistent with EMT in ectocervical cells with a significant reduction in E-cadherin and an increase in the vimentin expression compared to controls at 72 h. There was increased phosphorylation of receptor tyrosine kinases (RTKs), including Eph receptors, FGFR, PDGFRA/B, and DDR2, with downstream Ras/MAPK/ERK1/2 activation and upregulation of common EMT-related genes, TGFB SNAI2, PDGFRB, and SMAD2. Our study demonstrated that CSC induces EMT in ectocervical cells with the upregulation of EMT-related genes, expression of protein biomarkers, and activation of RTKs that regulate TGFB expression, and other EMT-related genes. Understanding the molecular pathways and environmental factors that initiate EMT in ectocervical cells will help delineate molecular targets for intervention and define the role of EMT in the initiation and progression of cervical intraepithelial neoplasia and CC.

Reevaluation of negative cervical conizations: Frequency, diagnostic errors, risk factors and management.

OBJECTIVE: Cervical conization is an effective treatment for precancerous lesions. However, in cases where no high-grade lesion is identified in the surgical specimen, managing these patients may be challenging due to the absence of established follow-up protocols for negative conizations. This study aimed to assess the negative conization rates at our institution by histopathological review, identify diagnostic errors, possible risk and recurrence factors and propose follow-up strategies for this group of patients. METHODS: A retrospective study from January-2010 to December-2020 analyzed patients with negative conization including all surgical techniques and procedure indications. Biopsy and cervical conizations slides were reviewed and patients who kept a negative result underwent deeper levels sectioning of the paraffin blocks with immunohistochemical stains application: p16, Ki-67 and geminin. Data were compared with a control group composed by 29 women with CIN3. RESULTS: Out of 1022 conizations, 186 were negative (18.1%), with 151 cases selected for the study after excluding 35 patients. Following pathology review, 4 patients were excluded due to false-positive cervical biopsy results, 16 for false-negative conization results and 9 for hidden dysplasia identified after deeper sectioning. The remaining 122 patients were considered truly negative cones (11.9%) and exhibited IHC staining with p16 positive in 20.4% of cases, low Ki-67 expression, and low geminin score in most cases. Specimens with CIN 1 had higher prevalence of p16 staining, Ki-67 expression and geminin score when compared to absence of neoplasia, nevertheless geminin had no statistical difference. Older age, higher parity and IHC pattern with negative p16, low Ki-67 and geminin expressions were identified as risk factors for negative cones (p<0.05). Only 10 patients recurred for high-grade lesions, with no statistically significant risk factors identified. CONCLUSIONS: The negative conization rate was 11.9%, with diagnostic errors identified across pre-surgical biopsy, cone specimen, and deeper levels. Risk factors included older age, higher parity, low expression of p16, Ki-67 and geminin (p<0.05). Recurrence represented 8.1% of the negative cones, without identification of statistically significant risk factors. Pathological review with deeper level sections and 2-year follow-up are recommended for patients with negative conizations.

Endometrial Cancer Detection by DNA Methylation Analysis in Cervical Papanicolaou Brush Samples.

Background: Endometrial cancer (EC) is the leading gynecological cancer worldwide, yet current EC screening approaches are not satisfying. The purpose of this retrospective study was to evaluate the feasibility and capability of DNA methylation analysis in cervical Papanicolaou (Pap) brush samples for EC detection. Methods: We used quantitative methylation-sensitive PCR (qMS-PCR) to determine the methylation status of candidate genes in EC tissue samples, as well as cervical Pap brushes. The ability of RASSF1A and HIST1H4F to serve as diagnostic markers for EC was then examined in cervical Pap brush samples from women with endometrial lesions of varying degrees of severity. Results: Methylated RASSF1A and HIST1H4F were found in EC tissues. Further, methylation of the two genes was also observed in cervical Pap smear samples from EC patients. Methylation levels of RASSF1A and HIST1H4F increased as endometrial lesions progressed, and cervical Pap brush samples from women affected by EC exhibited significantly higher levels of methylated RASSF1A and HIST1H4F compared to noncancerous controls (P < .001). Receiver operating characteristic (ROC) curves and area under the curve (AUC) analyses revealed RASSF1A and HIST1H4F methylation with a combined AUC of 0.938 and 0.951 for EC/pre-EC detection in cervical Pap brush samples, respectively. Conclusion: These findings demonstrate that DNA methylation analysis in cervical Pap brush samples may be helpful for EC detection, broadening the scope of the commonly used cytological screening. Our proof-of-concept study provides new insights into the field of clinical EC diagnosis.

Synergistic effect of human uterine cervical mesenchymal stem cell secretome and paclitaxel on triple negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer and, despite its adverse effects, chemotherapy is the standard systemic treatment option for TNBC. Since, it is of utmost importance to consider the combination of different agents to achieve greater efficacy and curability potential, MSC secretome is a possible innovative alternative. METHODS: In the present study, we proposed to investigate the anti-tumor effect of the combination of a chemical agent (paclitaxel) with a complex biological product, secretome derived from human Uterine Cervical Stem cells (CM-hUCESC) in TNBC. RESULTS: The combination of paclitaxel and CM-hUCESC decreased cell proliferation and invasiveness of tumor cells and induced apoptosis in vitro (MDA-MB-231 and/or primary tumor cells). The anti-tumor effect was confirmed in a mouse tumor xenograft model showing that the combination of both products has a significant effect in reducing tumor growth. Also, pre-conditioning hUCESC with a sub-lethal dose of paclitaxel enhances the effect of its secretome and in combination with paclitaxel reduced significantly tumor growth and even allows to diminish the dose of paclitaxel in vivo. This effect is in part due to the action of extracellular vesicles (EVs) derived from CM-hUCESC and soluble factors, such as TIMP-1 and - 2. CONCLUSIONS: In conclusion, our data demonstrate the synergistic effect of the combination of CM-hUCESC with paclitaxel on TNBC and opens an opportunity to reduce the dose of the chemotherapeutic agents, which may decrease chemotherapy-related toxicity.

Inhibition of cytosine 5-hydroxymethylation during progression of cancer precursor lesions in the uterine cervix.

Methylation and hydroxymethylation of cytosine moieties in CpG islands of specific genes are epigenetic processes shown to be involved in the development of cervical (pre)neoplastic lesions. We studied global (hydroxy)methylation during the subsequent steps in the carcinogenic process of the uterine cervix by using immunohistochemical protocols for the detection of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in paraffin-embedded tissues of the normal epithelia and (pre)malignant lesions. This approach allowed obtaining spatially resolved information of (epi)genetic alterations for individual cell populations in morphologically heterogeneous tissue samples. The normal ectocervical squamous epithelium showed a high degree of heterogeneity for both modifications, with a major positivity for 5-mC in the basal and parabasal layers in the ectocervical region, while 5-hmC immunostaining was even more restricted to the cells in the basal layer. Immature squamous metaplasia, characterized by expression of SOX17, surprisingly showed a decrease of 5-hmC in the basal compartments and an increase in the more superficial layers of the epithelium. The normal endocervical glandular epithelium showed a strong immunostaining reactivity for both modifications. At the squamocolumnar junctions, a specific 5-hmC pattern was observed in the squamous epithelium, resembling that of metaplasia, with the typical weak to negative reaction for 5-hmC in the basal cell compartment. The reserve cells underlying the glandular epithelium were also largely negative for 5-hmC but showed immunostaining for 5-mC. While the overall methylation status remained relatively constant, about 20% of the high-grade squamous lesions showed a very low immunostaining reactivity for 5-hmC. The (pre)malignant glandular lesions, including adenocarcinoma in situ (AIS) and adenocarcinoma showed a progressive decrease of hydroxymethylation with advancement of the lesion, resulting in cases with regions that were negative for 5-hmC immunostaining. These data indicate that inhibition of demethylation, which normally follows cytosine hydroxymethylation, is an important epigenetic switch in the development of cervical cancer.

Interstitial round needles should not be used for cervical cancer patient treated with intracavitary/ interstitial brachytherapy using a Venezia applicator : a case report.

BACKGROUND: Image-guided adaptive brachytherapy (IGABT) demonstrates an excellent local control rate and low toxicity while treating cervical cancer. For intracavitary/interstitial (IC/IS) brachytherapy (BT), several applicators are commercially available. Venezia (Elekta, Sweden), an advanced gynecological applicator, is designed for IC/IS BT for treating locally advanced cervical cancer. There are two types of interstitial needles for the Venezia applicator: the round needle and sharp needle. Generally, a round needle is safer because it has less risk of damaging the organ at risk than a sharp needle. However, there is currently no evidence to suggest that a round needle is better than a sharp needle for the Venezia applicator in IC/IS BT. Herein, we documented our experience of using both round and sharp needles with the Venezia applicator in IC/IS BT for cervical cancer. CASE PRESENTATION: A 71-year-old woman was diagnosed with clinical stage T2bN0M0 and the International Federation of Gynecology and Obstetrics stage IIB cervical squamous cell carcinoma. Definitive therapy, including a high-dose-rate BT boost, was planned using a round needle with the Venezia applicator in IC/IS BT. After inserting four interstitial round needles during the first and second BT sessions, an unexpectedly large gap (1.5 cm) was detected between the cervix and ovoid. We therefore used a sharp needle with the Venezia applicator for IC/IS BT during the third and fourth BT sessions. Three sharp needles were firmly inserted during the third and fourth BT sessions. CONCLUSIONS: The study findings suggest that the interstitial round needle should not be used for cervical cancer patients undergoing IC/IS BT using the Venezia applicator.

Aggressive precursor B cell ALL of cervix with obstructive uropathy.

Involvement of the cervix with acute lymphoblastic leukaemia (ALL) is extremely rare. In this case report, we discuss an unmarried woman in her early 20s, who presented in the emergency with lower abdominal pain and irregular vaginal bleeding for 1 month. Clinical examination and imaging revealed a large cervical mass probably neoplastic with obstructive uropathy. On evaluation, she was diagnosed incidentally with CALLA-positive precursor B cell ALL in peripheral blood flow cytometry. Involvement of B cell ALL in cervical mass was confirmed by histopathological examination of cervical biopsy and immunohistochemistry markers. Her history was not suggestive of signs and symptoms pertaining to leukaemia. Literature is sparse with only a few cases reporting cervical leukaemic infiltration. The present case report is a rarest case where the primary/initial presentation of precursor B cell ALL was seen with cervical involvement and obstructive uropathy mimicking characteristics of advanced cervical malignancy.

Concomitant ectopic Enterobius vermicularis infection in uterine cervical cancer.

BACKGROUND: Enterobius vermicularis (E. vermicularis), also referred to as pinworm, is a widespread human intestinal parasite which predominantly occurs in young children, making their caretakers a population at risk for the transmission of this helminth. It can occasionally affect extraintestinal organs and tissues, including the female genital tract. Infestation can be asymptomatic or manifest as different kinds of gynaecological disorders, such as pelvic inflammation mimicking tumours, abnormal uterine bleeding, or vaginitis. Diagnosis is made by identifying ova in the sample collected from the perineal skin using a transparent adhesive tape or microscopic examination of resected tissue. Mebendazole is the first-line medication and should also be administered to all household members. CASE PRESENTATION: We present a case of a patient who had undergone surgery for invasive cervical cancer with an accidental finding of E. vermicularis eggs in the cervix. CONCLUSIONS: Although not very common, infestation with E. vermicularis should be considered in differential diagnoses of various gynaecological disorders accompanied by histological findings of granulomatous inflammation.

Efficacy of Lidocaine Spray for Pain Reduction during Colposcopy-Directed Cervical Biopsies: A Randomized Controlled Trial.

Objectives: The objective of this study was to evaluate the efficacy of lidocaine spray in reducing the pain during colposcopy-directed cervical biopsy (CDB). Methods: From December 2017 to February 2019, 312 women undergoing CDBs were enrolled. The participants were randomized to three groups: group 1 (lidocaine spray), in which lidocaine spray was applied thoroughly to the cervix; group 2 (placebo), in which normal saline was applied thoroughly to the cervix; and group 3 (control), in which no anesthetic agent was applied to the cervix. Each woman completed a 10 cm visual analog scale to classify the subjective pain experience at three time points: baseline, immediately after biopsy, and 10 min after the procedure. The primary outcome of this study was the biopsy pain score. Results: The 312 enrolled women were randomly assigned to the three groups, amounting to 104 women per group. The clinical and pathological characteristics of the participants in all groups were comparable. The baseline, the biopsy, and the post-procedure pain scores were comparable among the three groups. There was a significant increase in the pain score from baseline to biopsy and from baseline to post-procedure in each group. The pain-score changes from baseline to biopsy in the lidocaine spray group significantly decreased when compared with the normal saline group (<0.001), and tended to decrease, though not significantly (p = 0.06), when compared with the control group. No complication with the intervention was observed. Conclusions: The application of lidocaine spray to the cervix has the benefit of reducing the pain associated with CDBs by a small amount. However, the intervention is safe and may be considered in nulliparous and/or overly anxious women undergoing the procedure.

Expression of the O-Linked N-Acetylglucosamine-containing Epitope H (O-GlcNAcH) in Human Uterine Cervical Mucosa.

BACKGROUND/AIM: Epitope H contains an O-linked N-acetylglucosamine (O-GlcNAcH) residue in a specific conformation or environment, recognized by a site-specific monoclonal mouse IgM antibody H. O-GlcNAcH occurs in several normal and pathological cells and in several polypeptides, including keratin-8 and vimentin, on the latter in cells under stress. MATERIALS AND METHODS: In this work, we studied the distribution of O-GlcNAcH on cells of endocervical mucosa in 60 specimens of endocervical curettings, 10 of which contained 15 inflamed polyps. RESULTS: In our results, expression of O-GlcNAcH was weak in the mucosa with <5% mucin-secreting cells and up to 30% of the polyps staining positively. All non-ciliated, non-mucin-secreting cells, normal and hyperplastic 'reserve' cells, as well as the cells of immature squamous metaplasia, showed strong diffuse cytoplasmic staining for O-GlcNAcH. In mature squamous epithelium, fewer than 5% of basal cells and all the intermediate and superficial cells showed cytoplasmic staining for O-GlcNAcH, whereas parabasal cells were negative. All ciliated cells showed patchy or diffuse cytoplasmic staining. Nuclear staining for O-GlcNAcH was weak with fewer than 5% of hyperplastic 'reserve' and ciliated cells staining positively. Moreover, mucosal fibroblasts were negative, whereas all stromal cells of the polyps showed strong cytoplasmic staining for O-GlcNAcH. CONCLUSION: O-GlcNAcH is: a) differentially expressed among the cellular elements of mucosa and polyps, b) upregulated in mucin-secreting cells of polyps, c) induced in stromal cells of inflamed polyps, and d) can be used as a marker to differentiate between 'reserve' (positive) and parabasal (negative) cells, which have similar morphology using conventional cytological stains.

[Application of optical coherence tomography in the evaluation of cervical lesions: a multicenter study].

Objective: To explore the value of optical coherence tomography (OCT) imaging system in evaluating cervical lesions in vivo. Methods: A total of 1 214 patients with cervical lesions were collected from January 2020 to December 2021 in the Third Affiliated Hospital of Zhengzhou University, Maternal and Chlid Heaith Hospital of Gushi County, Xinyang City, Henan Province, and Maternal and Chlid Heaith Hospital of Sui County, Shangqiu City, Henan Province. The age of the patients was (38.9±10.5) years (range: 16-77 years). All patients underwent in vivo cervical OCT examination and cervical biopsy pathology examination, and summarized the OCT image features of in vivo cervical lesions. Using the pathological diagnosis as the "gold standard", the accuracy, specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of OCT image interpretation results were evaluated, as well as the consistency of OCT image diagnosis and pathological diagnosis. At the same time, the in vivo cervical OCT imaging system, as a newly developed screening tool, was compared with the traditional combined screening of human papillomavirus (HPV) and Thinprep cytologic test (TCT), to assess the screening effect. Results: By comparing the OCT images of the cervix in vivo with the corresponding HE images, the OCT image characteristics of the normal cervix and various types of cervical lesions in vivo were summarized. The accuracy, sensitivity, specificity, PPV and NPV of OCT image in the diagnosis of high-grade squamous intraepithelial lesion (HSIL) and above (HSIL+) were 93.4%, 88.5%, 95.0%, 85.0% and 96.2%, respectively. The accuracy, sensitivity, specificity, PPV and NPV of OCT for low-grade squamous intraepithelial lesion (LSIL) were 84.7%, 61.7%, 96.3%, 89.3% and 83.2%, respectively. The consistency between OCT image diagnosis and pathological diagnosis was strong (Kappa value was 0.701).The accuracy, sensitivity and specificity of OCT screening, HPV and TCT combined screening were 83.7% vs 64.9% (χ²=128.82, P<0.001), 77.8% vs 64.5% (χ²=39.01, P<0.001), 91.8% vs 65.4% (χ²=98.12, P<0.001), respectively. The differences were statistically significant. Conclusions: OCT imaging system has high sensitivity and specificity in the evaluation of cervical lesions in vivo, and has the characteristics of non-invasive, real-time and high efficiency. OCT examination is expected to become an effective method for the diagnosis of cervical lesions and cervical cancer screening.

Ewing sarcoma of the cervix: an unusual site of presentation.

Ewing sarcoma is an exceedingly rare form of cancer that affects the cervix. It falls within the spectrum of neoplastic diseases known as Ewing's family of tumours, typically observed in osseous tissues. A woman in her 40s, experiencing symptoms of leucorrhoea and transvaginal bleeding that commenced 3 months before her consultation, was referred to our gynaecological oncology clinic with a preliminary diagnosis of ovarian teratoma. A colposcopy procedure was conducted unveiling a complete loss of cervical anatomy with friable and malodorous tissue. Pelvic ultrasound identified a lesion of uncertain origin in the cervix, suggestive of malignancy. Histopathological assessment of cervical biopsy specimens confirmed the presence of a small, round, blue cell neoplasm consistent with Ewing sarcoma. She underwent chemotherapy and pelvic radiotherapy, achieving complete remission 9 months after diagnosis, without experiencing any systemic adverse effects or sequelae.

Evaluation of the diagnostic performance of colposcopy in the detection of cervical high-grade squamous intraepithelial lesions among women with transformation zone type 3.

BACKGROUND: Inaccurate colposcopy diagnosis may lead to inappropriate management and increase the incidence of cervical cancer. This study aimed to evaluate the diagnostic accuracy of colposcopy in the detection of histologic cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with transformation zone type 3 (TZ3). METHODS: Records from 764 patients with TZ3 who underwent colposcopy-directed biopsy and/or endocervical curettage in Putuo Hospital China between February 2020 and March 2023 were retrospectively collected. Colposcopy was carried out based on 2011 International Federation of Cervical Pathology and Colposcopy (IFCPC) and Colposcopy nomenclature. The diagnostic performance of colposcopy for identifying CIN2 + was evaluated compared with biopsies. The Kappa and McNemar tests were used to perform statistical analyses. RESULTS: Among the study population, 11.0% had pathologic CIN2+. The relative sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of colposcopy for histologic CIN2 + were 51.2%, 96.5%, 64.2% and 94.1%, respectively. The senior colposcopists (80.6%) had a higher colposcopic accuracy to diagnose histologic CIN2 + than junior colposcopists (68.6%). In subgroup analyses, age group ≥ 60 years (70.3%) showed lowest diagnostic accuracy when compared with age groups of < 45 years (84.4%) and 45-59 years (74.9%). CONCLUSION: Our findings suggest an increased risk of diagnostic inaccuracy of colposcopy in identifying CIN2 + in those ≥ 60 years of age with TZ3, and the accuracy of colposcopy is required to be further improved.

MKRN1 regulates the expression profiles and transcription factor activity in HeLa cells inhibition suppresses cervical cancer cell progression.

Cervical cancer is one of the most common gynecologic malignancies worldwide, necessitating the identification of novel biomarkers and therapeutic targets. This study aimed to investigate the significance of MKRN1 in cervical cancer and explore its potential as a diagnostic marker and therapeutic target. The results indicated that MKRN1 expression was up-regulated in cervical cancer tissues and correlated with advanced tumor stage, higher grade, and poor patient survival. Functional studies demonstrated that targeting MKRN1 effectively inhibited cell proliferation, migration, and invasion, highlighting its critical role in tumor progression and metastasis. Moreover, the knockdown of MKRN1 resulted in altered expression patterns of six transcription factor-encoding genes, revealing its involvement in gene regulation. Co-expression network analysis unveiled complex regulatory mechanisms underlying the effects of MKRN1 knockdown on gene expression. Furthermore, the results suggested that MKRN1 might serve as a diagnostic marker for personalized treatment strategies and a therapeutic target to inhibit tumor growth, metastasis, and overcome drug resistance. The development of MKRN1-targeted interventions might hold promise for advancing personalized medicine approaches in cervical cancer treatment. Further research is warranted to validate these findings, elucidate underlying mechanisms, and translate these insights into improved management and outcomes for cervical cancer patients.

Mature solid teratoma of the uterine cervix: A rare case report and review of the literature.

RATIONALE: Most of the mature teratomas are found in the ovaries. Extragonadal teratomas are extremely rare. To date, there are only a handful of reports of uterine cervical teratomas documented in the English literature. PATIENT CONCERNS: Herein we describe a rare case of a 40-year-old patient who was presented to our hospital for a cervical polypoid mass, which was finally confirmed to be mature solid teratoma in uterine cervix. DIAGNOSES: Histological examination of the polypoid mass was found to consist of ciliated pseudostratified columnar respiratory epithelium, intestinal epithelium and smooth muscle tissue, adipose tissue and mature glial component, epidermis, and skin adnexa. Meanwhile, no history of abortion, dilatation, and curettage was present in this patient, so implantation of fetal tissue was excluded. Therefore, we make a diagnosis of uterine cervical mature teratoma. INTERVENTIONS: Tumorectomy was performed after discovering the cervical polypoid mass. OUTCOMES: The patient had been followed-up for next 3 months after surgery and no recurrence was documented until now. LESSONS: Though teratomas of the uterine cervix are extremely rare, more attention should be paid on this rare but possible tumor for appropriate treatment in these patients.

Cervical clear cell carcinoma: Case report and literature review.

RATIONALE: Clear cell carcinoma (CCC) is a highly invasive malignant tumor. CCCs of the female reproductive system occur mostly in the endometrium and ovaries and rarely in the cervix. So, it is difficult to diagnose cervical clear cell carcinoma (CCAC) on imaging. This report helps to further deepen our understanding of CCAC. PATIENT CONCERNS: A 39-year-old female patient presented with vaginal discharge with no obvious cause, elevated levels of carcinoembryonic antigen (CEA), CA125, CA153, and squamous cell carcinoma antigen (SCC), and underwent ultrasonography (US) CT and MRI examination in our hospital, which showed a mass in the cervix of the uterus, considered of cervical squamous carcinoma. DIAGNOSES: The cervix biopsy guided by vaginoscope biopsy and immunohistochemistry confirmed CCAC, combined Magnetic Resonance Imaging examination, CCAC with pelvic lymph node metastasis was considered. INTERVENTIONS AND OUTCOMES: The patient refused further treatment and was discharged from hospital. LESSONS: CCAC exhibited no specific symptoms, and is slightly different from cervical squamous carcinoma in image features, mainly relying on immunohistochemistry for diagnosis. The reported case raised awareness of CCAC.

Atypical glandular cells in Pap tests: cytology-histology correlation and risk assessment with human papillopmavirus (HPV) testing.

INTRODUCTION: Atypical glandular cells (AGC) represent less than 1% of Pap test cases and include a variety of lesions in both the cervix and endometrium. The study aimed to investigate the cytology-histology correlation in AGC patients and to evaluate the clinical utility of hrHPV testing in this diagnostic context. MATERIALS AND METHODS: We identified 491 atypical glandular cells (AGC) cases in our quality analysis (QA) database of 336,064 Pap tests interpreted between March 1, 2013 and July 12, 2016. Of these, 251 cases had follow-up biopsies with hrHPV tests in 148 cases. RESULTS: The most common histologic diagnosis associated with AGC was normal/benign or low-grade lesions, comprising 55% of cervical biopsies and 24% of endometrial biopsies. High-grade lesions were identified in 21% of follow-up biopsies. In patients with AGC cytology, a positive hrHPV test significantly increased the likelihood of cervical HSIL or above lesions on biopsy by 26.4 times (OR = 26.4, 95% CI: 5.8-119.4, P < 0.0001). A positive genotyping result for HPV 16 dramatically increased the likelihood of cervical HSIL or above lesions on biopsy (OR = 84, 95% CI: 12.0-590.5, P < 0.0001). The HPV test had a negative predictive value of 97% (CI: 85%-100%). CONCLUSIONS: Our study confirms that AGC is a significant diagnosis with an overall risk for high-grade cervical or endometrial lesions as high as 21%. hrHPV testing with genotyping is an effective tool for identifying high-risk individuals within the AGC population, with excellent positive and negative predictive values. This approach is valuable for clinical risk stratification and differential diagnosis in patients with AGC cytology.

A nomogram of preoperative indicators predicting lymph vascular space invasion in cervical cancer.

PURPOSE: To develop predictive nomograms of lymph vascular space invasion (LVSI) in patients with early-stage cervical cancer. METHODS: We identified 403 patients with cervical cancer from the Affiliated Hospital of Jiangnan University from January 2015 to December 2019. Patients were divided into the training set (n = 242) and the validation set (n = 161), with patients in the training set subdivided into LVSI (+) and LVSI (-) groups according to postoperative pathology. Preoperative hematologic indexes were compared between the two subgroups. Univariate and multivariate logistic regression analyses were used to analyze the independent risk factors for LVSI, from which a nomogram was constructed using the R package. RESULTS: LVSI (+) was present in 94 out of 242 patients in the training set, accompanied by a significant increase in the preoperative squamous cell carcinoma antigen (SCC), white blood cells (WBC), neutrophil (NE), platelet (PLT), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and tumor size (P < 0.05). Univariate analysis showed that SCC, WBC, NE, NLR, PLR, SII, and tumor size were correlated with LVSI (P < 0.05), and multivariate analysis showed that tumor size, SCC, WBC, and NLR were independent risk factors for LVSI (P < 0.05). A nomogram was correspondingly established with good performance in predicting LVSI [training: ROC-AUC = 0.845 (95% CI: 0.731-0.843) and external validation: ROC-AUC = 0.704 (95% CI: 0.683-0.835)] and high accuracy (training: C-index = 0.787; external validation: C-index = 0.759). CONCLUSION: The nomogram based on preoperative tumor size, SCC, WBC, and NLR had excellent accuracy and discriminative capability to assess the risk of LVSI in early-stage cervical cancer patients.