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International Journal of Molecular... Nov 2021Cervical cancer is one of the most common types of carcinomas causing morbidity and mortality in women in all countries of the world. At the moment, the oncology,... (Review)
Review
Cervical cancer is one of the most common types of carcinomas causing morbidity and mortality in women in all countries of the world. At the moment, the oncology, oncobiology, and oncomorphology of cervical cancer are characterized by the accumulation of new information; various molecular biological, genetic, and immunohistochemical methods of investigation of the mechanisms of cervical carcinogenesis are tested and applied; targeted antitumour drugs and diagnostic, prognostic, and predictive biomarkers are being searched for. Many issues of the etiopathogenesis of cervical cancer have not been sufficiently studied, and the role of many biomarkers characterizing various stages of cervical carcinogenesis remains unclear. Therefore, the target of this review is to systematize and understand several problems in the pathogenesis of cervical cancer and to evaluate the significance and role of biomarkers in cervical carcinogenesis.
Topics: Biomarkers, Tumor; Carcinogenesis; Carcinoma, Squamous Cell; Cervix Uteri; Female; Humans; Uterine Cervical Neoplasms
PubMed: 34830452
DOI: 10.3390/ijms222212571 -
International Journal of Molecular... Nov 2022Cervical cancer is the fourth most common cancer in women. It is the leading cause of female deaths in developing countries. Most of these cervical neoplasms are... (Review)
Review
Cervical cancer is the fourth most common cancer in women. It is the leading cause of female deaths in developing countries. Most of these cervical neoplasms are represented by squamous lesions. Cervical adenocarcinoma causes about a quarter of cervical cancers. In contrast to squamous lesions, cervical glandular disease is HPV-negative in about 15-20% of cases. HPV-negative cervical adenocarcinomas typically present in advanced stages at clinical evaluation, resulting in a poorer prognosis. The overall and disease-free survival of glandular lesions is lower than that of squamous lesions. Treatment options require definitive treatments, as fertility-sparing is not recommended. Moreover, the impact of HPV vaccination and primary HPV screening is likely to affect these lesions less; hence, the interest in this challenging topic for clinical practice. An updated review focusing on clinical and molecular characterization, prognostic factors, and therapeutic options may be helpful for properly managing such cervical lesions.
Topics: Female; Humans; Uterine Cervical Neoplasms; Papillomaviridae; Papillomavirus Infections; Cervix Uteri; Adenocarcinoma; Carcinoma, Squamous Cell
PubMed: 36499345
DOI: 10.3390/ijms232315022 -
BMC Cancer May 2018Neuroendocrine carcinoma of the cervix (NECC) is a rare variant of cervical cancer. The prognosis of women with NECC is poor and there is no standardized therapy for...
BACKGROUND
Neuroendocrine carcinoma of the cervix (NECC) is a rare variant of cervical cancer. The prognosis of women with NECC is poor and there is no standardized therapy for this type of malignancy based on controlled trials.
METHODS
We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify clinical trials describing the management and outcome of women with NECC.
RESULTS
Three thousand five hundred thirty-eight cases of NECC in 112 studies were identified. The pooled proportion of NECC among women with cervical cancer was 2303/163470 (1.41%). Small cell NECC, large cell NECC, and other histological subtypes were identified in 80.4, 12.0, and 7.6% of cases, respectively. Early and late stage disease presentation were evenly distributed with 1463 (50.6%) and 1428 (49.4%) cases, respectively. Tumors expressed synaptophysin (424/538 cases; 79%), neuron-specific enolase (196/285 cases; 69%), chromogranin (323/486 cases; 66%), and CD56 (162/267; 61%). The most common primary treatment was radical surgery combined with chemotherapy either as neoadjuvant or adjuvant chemotherapy, described in 42/48 studies. Radiotherapy-based primary treatment schemes in the form of radiotherapy, radiochemotherapy, or radiotherapy with concomitant or followed by chemotherapy were also commonly used (15/48 studies). There is no standard chemotherapy regimen for NECC, but cisplatin/carboplatin and etoposide (EP) was the most commonly used treatment scheme (24/40 studies). Overall, the prognosis of women with NECC was poor with a mean recurrence-free survival of 16 months and a mean overall survival of 40 months. Immune checkpoint inhibitors and targeted agents were reported as being active in three case reports.
CONCLUSION
NECC is a rare variant of cervical cancer with a poor prognosis. Multimodality treatment with radical surgery and neoadjuvant/adjuvant chemotherapy with cisplatin and etoposide with or without radiotherapy is the mainstay of treatment for early stage disease while chemotherapy with cisplatin and etoposide or topotecan, paclitaxel, and bevacizumab is appropriate for women with locally advanced or recurrent NECC. Immune checkpoint inhibitors may be beneficial, but controlled evidence for their efficacy is lacking.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Neuroendocrine; Cervix Uteri; Chemoradiotherapy, Adjuvant; Clinical Trials as Topic; Female; Humans; Hysterectomy; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Survival Rate; Treatment Outcome; Uterine Cervical Neoplasms
PubMed: 29728073
DOI: 10.1186/s12885-018-4447-x -
Virchows Archiv : An International... Nov 2019Endocervical adenocarcinomas (ECAs) are currently classified according to the 2014 World Health Organization (WHO) system, which is predominantly based on descriptive... (Review)
Review
Endocervical adenocarcinomas (ECAs) are currently classified according to the 2014 World Health Organization (WHO) system, which is predominantly based on descriptive morphologic characteristics, considers factors bearing minimal etiological, clinical, or therapeutic relevance, and lacks sufficient reproducibility. The 2017 International Endocervical Adenocarcinoma Criteria and Classification (IECC) system was developed by a group of international collaborators to address these limitations. The IECC system separates ECAs into two major groups-those that are human papillomavirus-associated (HPVA) and those that are non-HPV-associated (NHPVA)-based on morphology (linked to etiology) alone, precluding the need for an expensive panel of immunohistochemical markers for most cases. The major types of HPVA ECA include the usual (with villoglandular and micropapillary architectural variants) and mucinous types (not otherwise specified [NOS], intestinal, signet-ring, and invasive stratified mucin-producing carcinoma). Invasive adenocarcinoma NOS is morphologically uninformative, yet considered part of this group when HPV positive. NHPVA ECAs include gastric, clear cell, endometrioid, and mesonephric types. The IECC system is supported by demographic and clinical features (HPVA ECAs develop in younger patients, are smaller, and are diagnosed at an earlier stage), p16/HPV status (almost all HPVA ECAs are p16 and/or HPV positive), prognostic parameters (NHPVA ECAs more often have lymphovascular invasion, lymph node metastases, and are Silva pattern C), and survival data (NHPVA ECAs are associated with worse survival). A move from the morphology-based WHO system to the IECC system will likely provide clinicians with an improved means to diagnose and classify ECAs, and ultimately, to better personalize treatment for these patients.
Topics: Adenocarcinoma; Cervix Uteri; Female; Humans; Lymphatic Metastasis; Papillomaviridae; Papillomavirus Infections; Prognosis; Reproducibility of Results; Uterine Cervical Neoplasms
PubMed: 31209635
DOI: 10.1007/s00428-019-02601-0 -
Frontiers in Immunology 2022Cervical cancer (CC) is one of the most common malignancy in women worldwide. It is characterized by a natural continuous phenomenon, that is, it is in the initial stage...
Cervical cancer (CC) is one of the most common malignancy in women worldwide. It is characterized by a natural continuous phenomenon, that is, it is in the initial stage of HPV infection, progresses to intraepithelial neoplasia, and then develops into invasion and metastasis. Determining the complexity of tumor microenvironment (TME) can deepen our understanding of lesion progression and provide novel therapeutic strategies for CC. We performed the single-cell RNA sequencing on the normal cervix, intraepithelial neoplasia, primary tumor and metastatic lymph node tissues to describe the composition, lineage, and functional status of immune cells and mesenchymal cells at different stages of CC progression. A total of 59913 single cells were obtained and divided into 9 cellular clusters, including immune cells (T/NK cells, macrophages, B cells, plasma cells, mast cells and neutrophils) and mesenchymal cells (endothelial cells, smooth muscle cells and fibroblasts). Our results showed that there were distinct cell subpopulations in different stages of CC. High-stage intraepithelial neoplasia (HSIL) tissue exhibited a low, recently activated TME, and it was characterized by high infiltration of tissue-resident CD8 T cell, effector NK cells, Treg, DC1, pDC, and M1-like macrophages. Tumor tissue displayed high enrichment of exhausted CD8 T cells, resident NK cells and M2-like macrophages, suggesting immunosuppressive TME. Metastatic lymph node consisted of naive T cell, central memory T cell, circling NK cells, cytotoxic CD8+ T cells and effector memory CD8 T cells, suggesting an early activated phase of immune response. This study is the first to delineate the transcriptome profile of immune cells during CC progression using single-cell RNA sequencing. Our results indicated that HSIL exhibited a low, recently activated TME, tumor displayed immunosuppressive statue, and metastatic lymph node showed early activated phase of immune response. Our study enhanced the understanding of dynamic change of TME during CC progression and has implications for the development of novel treatments to inhibit the initiation and progression of CC.
Topics: Cervix Uteri; Endothelial Cells; Female; Humans; Lymph Nodes; Precancerous Conditions; Transcriptome; Tumor Microenvironment; Uterine Cervical Neoplasms
PubMed: 35812401
DOI: 10.3389/fimmu.2022.897366 -
The Journal of Experimental Medicine May 1953The cells of a human epithelial cancer cultivated en masse have been shown to support the multiplication of all three types of poliomyelitis virus. These cells (strain...
Studies on the propagation in vitro of poliomyelitis viruses. IV. Viral multiplication in a stable strain of human malignant epithelial cells (strain HeLa) derived from an epidermoid carcinoma of the cervix.
The cells of a human epithelial cancer cultivated en masse have been shown to support the multiplication of all three types of poliomyelitis virus. These cells (strain HeLa of Gey) have been maintained in vitro since their derivation from an epidermoid carcinoma of the cervix in February, 1951. As the virus multiplied it caused in from 12 to 96 hours degeneration and destruction of the cancer cells. The specific destructive effect of the virus was prevented by adding homotypic antibody to the cultures but not by adding heterotypic antibodies. Methods for the preparation of large numbers of replicate cultures with suspensions of strain HeLa cells were described. The cells in suspension were readily quantitated by direct counts in a hemocytometer. A synthetic solution that maintains cellular viability was employed for viral propagation. The experimental results demonstrate the usefulness of strain HeLa cells for (a) the quantitation of poliomyelitis virus, (b) the measurement of poliomyelitis antibodies, and (c) the production of virus.
Topics: Antibodies; Antibodies, Heterophile; Carcinoma, Squamous Cell; Cervix Uteri; Female; HeLa Cells; Humans; In Vitro Techniques; Poliomyelitis; Poliovirus; Tissue Culture Techniques; Viruses
PubMed: 13052828
DOI: 10.1084/jem.97.5.695 -
Journal of Cancer Research and... Apr 2023Stem cells exist in niches in the cervical tissue at squamocolumnar junction, which when infected with HR-Human Papilloma Virus undergo malignant transformation to...
BACKGROUND
Stem cells exist in niches in the cervical tissue at squamocolumnar junction, which when infected with HR-Human Papilloma Virus undergo malignant transformation to cancer stem cells and have a role in carcinogenesis and metastasis. The expression of CD44, P16, and Ki67 in high-grade squamous intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) is assessed in this study.
MATERIALS AND METHODS
Twenty-six cases each of normal cervix, HSIL, and SCC of cervix cases were subjected to immunohistochemistry markers; p16, Ki-67, and CD44. The association of expression of these markers between normal, HSIL, SCC cervix, and clinic-pathological parameters was statistically analyzed. P < 0.05 was considered significant.
RESULTS
Of 26 cases of HSIL, 61.5%, 7.7%, and 30.8% cases were positive, ambiguous, and negative respectively for p16 expression. About 11.5%, 53.8%, and 34.6% of cases were strongly positive, positive, and weakly positive, respectively, for Ki-67 expression. About 42.3%, 42.3%, and 15.4% cases were strongly positive, positive, and weakly positive, respectively, for CD44 expression. Among 26 cases of SCC of the cervix 92.3% and 7.7% were positive and ambiguous respectively. About 73.1% and 26.9% of cases were strongly positive and positive, respectively, for Ki-67 expression. 65.4%, 30.8%, and 3.8% of cases were strongly positive, positive, and weakly positive, respectively, for CD44 expression. p16, Ki-67, and CD44 expression between the three groups were statistically significant. p16 expression versus FIGO stage including lymph node involvement and CD44 expression versus lymph node involvement in carcinoma cervix was statistically significant.
CONCLUSION
Expression of p16, Ki-67, and CD44 increases as the lesion progress from normal to HSIL to carcinoma cervix. p16 and CD44 expression increase with lymph node involvement. P16 expression was maximum in Stage II than Stage III.
Topics: Female; Humans; Cervix Uteri; Ki-67 Antigen; Uterine Cervical Neoplasms; Squamous Intraepithelial Lesions of the Cervix; Squamous Intraepithelial Lesions; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p16; Papillomavirus Infections; Biomarkers, Tumor; Hyaluronan Receptors
PubMed: 37148002
DOI: 10.4103/jcrt.jcrt_43_21 -
Asian Pacific Journal of Cancer... Mar 2022Cytokeratin (CK) proteins play a vital role in cancer diagnosis, of which,CK-7 is a prominent marker of squamocolumnar junction cells corresponding to the the initiating...
OBJECTIVES
Cytokeratin (CK) proteins play a vital role in cancer diagnosis, of which,CK-7 is a prominent marker of squamocolumnar junction cells corresponding to the the initiating site of cervical cancer.The current study is aimed to evaluate the expression pattern of CK-7 and to corelate with the clinicopathological features in patients with cervical dysplasia and invasive squamous cell carcinoma.
METHODOLOGY
The hysterectomy and biopsy specimens from women with cervical dysplasia (n=60) and carcinoma (n=60) were evaluated histopathologically and processed for immunohistochemistry (IHC) staining to assess for CK-7 expression. The relationship between CK-7 expression and tumor characteristics like histological type of cervical intraepithelial neoplasia (CIN), tumor type and grade was evaluated. Data was analyzed using the Chi-square test ,wherein the p value ≤ 0.05 were taken for statistical significance.
RESULTS
Positive CK-7 expression was observed in 25 (41.67%) dysplasia and in 34 (56.67%) carcinoma cases. Majority of the cases were CIN III (n=31, 51.67%), large cell non-keratinizing tumor type (n=54, 90%) and moderately differentiated grade of tumor (n=52, 86.67%), out of which 18 (58.1%), 34 (62.96%) and 30 (57.69%) cases were CK-7 positive, respectively. The difference in clinical diagnosis and tumor characteristics over CK-7 expression was significant (p<0.05). The pattern of CK-7 expression in dysplasia and carcinoma cases were diffuse in 23 (38.33%) and 31 (51.67%) respectively and patchy in 2 (3.33%) and 3 (5%) of them, respectively.
CONCLUSION
Significant positive CK-7 expression in cervical dysplasia and carcinoma indicates a good clinical course and its role as a useful predictable marker for cancer progression.
Topics: Carcinoma, Squamous Cell; Cervix Uteri; Female; Humans; Keratin-7; Uterine Cervical Neoplasms; Uterine Cervical Dysplasia
PubMed: 35345360
DOI: 10.31557/APJCP.2022.23.3.885 -
Biomedical Journal Oct 2023Small cell neuroendocrine carcinoma of the cervix (SCNECC) is an uncommon but aggressive uterine malignancy, the cause of which is generally associated with human... (Review)
Review
Small cell neuroendocrine carcinoma of the cervix (SCNECC) is an uncommon but aggressive uterine malignancy, the cause of which is generally associated with human papillomavirus (HPV) infection. A lack of clinical trials and evidence-based treatment guidelines poses therapeutic challenges to this rare tumor. At present, published data remain limited to case series and case reports. While clinical management has traditionally followed those of small cell neuroendocrine (SCNE) lung cancer relying on surgery, chemoradiation, and systemic chemotherapy, the prognosis remains dismal. Immune checkpoint inhibitors (ICIs), such as monoclonal antibodies that target programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1), atezolizumab and durvalumab have proven effective in extensive-stage SCNE lung cancer. Moreover, pembrolizumab has also proven beneficial effects when added onto chemotherapy in metastatic and recurrent HPV-associated non-SCNE cervical cancer. It holds promise to use ICIs in combination with chemoradiation to improve the clinical outcomes of patients with SCNECC. Future advances in our understanding of SCNECC biology - associated with the study of its genomic and molecular aberrations as well as knowledge from SCNE of lung and other extrapulmonary sites- would be helpful in discovering new molecular targets for drug development. Collaborative efforts and establishment of a SCNECC-specific biobank will be essential to achieve this goal.
Topics: Female; Humans; Uterine Cervical Neoplasms; Cervix Uteri; Papillomavirus Infections; Lung Neoplasms; Carcinoma, Neuroendocrine; B7-H1 Antigen
PubMed: 37467967
DOI: 10.1016/j.bj.2023.100633 -
Reproduction & Fertility Jul 2022The phenomenal extracellular matrix (ECM) remodelling of the cervix that precedes the myometrial contraction of labour at term or preterm appears to share some common... (Review)
Review
ABSTRACT
The phenomenal extracellular matrix (ECM) remodelling of the cervix that precedes the myometrial contraction of labour at term or preterm appears to share some common mechanisms with the occurrence, growth, invasion and metastasis of cervical carcinoma. Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are pivotal to the complex extracellular tissue modulation that includes degradation, remodelling and exchange of ECM components, which contribute to homeostasis under normal physiological conditions such as cervical remodelling during pregnancy and puerperium. However, in cancer such as that of the uterine cervix, this extensive network of extracellular tissue modulation is altered leading to disrupted cell-cell and cell-basement membrane adhesion, abnormal tissue growth, neovascularization and metastasis that disrupt homeostasis. Cervical ECM remodelling during pregnancy and puerperium could be a physiological albeit benign neoplasm. In this review, we examined the pathophysiologic differences and similarities in the role of MMPs in cervical remodelling and cervical carcinoma.
LAY SUMMARY
During pregnancy and childbirth, the cervix, which is the barrel-shaped lower portion of the womb that connects to the vagina, gradually softens, shortens and opens to allow birth of the baby. This process requires structural and biochemical changes in the cervix that are stimulated by enzymes known as matrix metalloproteinases. Interestingly, these enzymes also affect the structural and biochemical framework of the cervix during cervical cancer, although cervical cancers usually occur after infection by human papillomavirus. This review is intended to identify and explain the similarities and differences between the structural and chemical changes in the cervix during pregnancy and childbirth and the changes seen in cervical cancer.
Topics: Pregnancy; Female; Humans; Animals; Uterine Cervical Neoplasms; Cervix Uteri; Matrix Metalloproteinases; Extracellular Matrix; Carcinoma
PubMed: 37931406
DOI: 10.1530/RAF-22-0015