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Difficulty of cervical cancer diagnosis during pregnancy: A case series analysis of the clinicopathological characteristics and prognosis of cervical cancer diagnosed during pregnancy or within 6 months after parturition.

ABSTRACT: Due to the recent trend of women having children at an older age, the number of pregnancies complicated by cervical cancer has increased. In the present study, the clinical characteristics of patients with cervical cancer complicated by pregnancy were analyzed. The clinicopathological characteristics and prognosis of patients with cervical cancer during pregnancy who underwent treatment at Kyushu University Hospital from January 2008 to December 2017 were assessed retrospectively from their medical records. The medical information of patients diagnosed within 6 months after parturition was also evaluated as these patients were considered to be affected by cervical cancer during pregnancy. A total of 19 women were diagnosed with cervical cancer during pregnancy (median age, 33 years), three of whom were diagnosed as negative for intraepithelial lesion or malignancy at the initial visit to a previous clinic after pregnancy. The tumor stage was IA1 in one patient, IB1 in 16 patients, IB2 in one patient and IVB in one patient. The median gestational age at the time of cervical cancer diagnosis was 13 weeks. One patient died of cervical cancer during the follow-up period. An additional 12 patients were diagnosed within 6 months after parturition. The median age of these patients was 35.5 years. Cancer screening was performed in 10 patients during pregnancy, none of whom were diagnosed with cervical cancer, including three patients who were negative for intraepithelial lesion or malignancy. Of the 12 patients, one had tumor stage IA1, eight had IB1, two had IB2 and one had IIB. Three patients experienced recurrence, of whom one died of cervical cancer. Advanced cervical cancer was diagnosed both during pregnancy and within 6 months after parturition. Diagnosis of cervical cancer during pregnancy is difficult even at an advanced stage; however, rapid diagnosis and prompt multidisciplinary treatment are critical. Therefore, it is necessary to improve the accuracy of cervical cancer diagnosis, and to characterize tumor cells and their microenvironment, during pregnancy.

SUBMITTER: Sonoda K

PROVIDER: S-EPMC7890457 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Difficulty of cervical cancer diagnosis during pregnancy: A case series analysis of the clinicopathological characteristics and prognosis of cervical cancer diagnosed during pregnancy or within 6 months after parturition.

Sonoda Kenzo K Ohgami Tatsuhiro T Hachisuga Masahiro M Fujita Yasuyuki Y Okugawa Kaoru K Yahata Hideaki H Kato Kiyoko K

Molecular and clinical oncology 20210208 4

Due to the recent trend of women having children at an older age, the number of pregnancies complicated by cervical cancer has increased. In the present study, the clinical characteristics of patients with cervical cancer complicated by pregnancy were analyzed. The clinicopathological characteristics and prognosis of patients with cervical cancer during pregnancy who underwent treatment at Kyushu University Hospital from January 2008 to December 2017 were assessed retrospectively from their medi ...[more]

PMID: 33680458

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Project description:The cervix undergoes extensive remodeling throughout pregnancy and parturition. This process involves both ECM collagen degradation and cellular remodeling, which includes cell proliferation, transition and migration. Progesterone (P4) has been used clinically to delay cervical ripening and prevent preterm birth (PTB). However, the mechanisms by which progesterone affects cell transition and the migration of cervical epithelial and stromal cells are not yet fully known. In this study, we documented the role of a gestational level of P4 in the cellular transition (epithelial-mesenchymal transition [EMT] and mesenchymal-epithelial transition [MET]), cell migration, and inflammatory responses of endocervical epithelial cells (EEC) and cervical stromal cells (CSC). EEC and CSC were treated with LPS and P4 for 6 days. The epithelial:mesenchymal ratio (regular microscopy and cell shape index analysis), shift in intermediate filaments (immunofluorescence microscopy and western blot analyses for cytokeratin [CK]-18 and vimentin), adhesion molecules and transcription factors (western blot analyses for E-cadherin, N-cadherin and SNAIL), were used to determine growth characteristics and EMT and MET changes in EEC and CSC under the indicated conditions. To test cell remodeling, scratch assays followed by cellular analyses as mentioned above were performed. Inflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor α [TNFα]) and matrix metallopeptidase 9 (MMP9) were measured by ELISA. LPS promoted EMT (decreased cell shape index, decreased CK-18 and E-cadherin, increased vimentin, N-cadherin, and SNAIL), and increased IL-6 and MMP9 production by EEC. A gestational level of P4 prevented LPS-induced EMT in EEC and exhibited anti-inflammatory effect in both EEC and CSC. LPS slowed down wound healing in CSC but P4 treatment prevented the negative impact of LPS in CSC wound healing. These results may explain the cellular mechanisms by which P4 helps to stabilize the cervical epithelial barrier and preserve the mechanical and tensile strength of the cervical stromal layer, which are important in normal cervical remodeling processes during pregnancy.

Project description:BackgroundVaginal microbiome and the local innate immune defense, including the complement system, contribute to anti- and proinflammatory homeostasis during pregnancy and parturition. The relationship between commensal vaginal bacteria and complement activation during pregnancy and delivery is not known.ObjectiveTo study the association of the cervicovaginal microbiota composition to activation and regulation of the complement system during pregnancy and labor.Study designWe recruited women during late pregnancy (weeks 41 + 5 to 42 + 0, n=48) and women in active labor (weeks 38 + 4 to 42 + 2, n=25). Mucosal swabs were taken from the external cervix and lateral fornix of the vagina. From the same sampling site, microbiota was analyzed with 16S RNA gene amplicon sequencing. A Western blot technique was used to detect complement C3, C4 and factor B activation and presence of complement inhibitors. For semiquantitative analysis, the bands of the electrophoresed proteins in gels were digitized on a flatbed photo scanner and staining intensities were analyzed using ImageJ/Fiji win-64 software. Patient data was collected from medical records and questionnaires.ResultsThe vaginal microbiota was Lactobacillus-dominant in most of the samples (n=60), L. iners and L. crispatus being the dominant species. L. gasseri and L. jensenii were found to be more abundant during pregnancy than active labor. L. jensenii abundance correlated with C4 activation during pregnancy but not in labor. Gardnerella vaginalis was associated with C4 activation both during pregnancy and labor. The amount of L. gasseri correlated with factor B activation during pregnancy but not during labor. Atopobium vaginae was more abundant during pregnancy than labor and correlated with C4 activation during labor and with factor B activation during pregnancy. Activation of the alternative pathway factor B was significantly stronger during pregnancy compared to labor. During labor complement activation may be inhibited by the abundant presence of factor H and FHL1.ConclusionsThese results indicate that bacterial composition of the vaginal microbiota could have a role in the local activation and regulation of complement-mediated inflammation during pregnancy. At the time of parturition complement activation appears to be more strictly regulated than during pregnancy.

Project description:ImportanceOutcomes among patients with pregnancy-associated cancers (diagnosed during pregnancy or 1-year postpartum) other than breast cancer have received relatively little research attention. High-quality data from additional cancer sites are needed to inform the care of this unique group of patients.ObjectiveTo assess mortality and survival in premenopausal women with pregnancy-associated cancers, with a particular focus on cancers other than those of the breast.Design, setting, and participantsThis population-based retrospective cohort study included premenopausal women (aged 18-50 years) living in 3 Canadian provinces (Alberta, British Columbia, and Ontario) diagnosed with cancer between January 1, 2003, and December 31, 2016, with follow-up until December 31, 2017, or date of death. Data analysis occurred in 2021 and 2022.ExposuresParticipants were categorized as being diagnosed with cancer during pregnancy (from conception to delivery), during the postpartum period (up to 1 year after delivery), or during a time that was remote from pregnancy.Main outcomes and measuresOutcomes were overall survival at 1 and 5 years and time from diagnosis to death due to any cause. Cox proportional hazard models were used to estimate mortality adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs), adjusting for age at cancer diagnosis, cancer stage, cancer site, and days from diagnosis to first treatment. Meta-analysis was used to pool results across all 3 provinces.ResultsDuring the study period there were 1014, 3074, and 20 219 participants diagnosed with cancer during pregnancy, postpartum, and periods remote from pregnancy, respectively. One-year survival was similar across the 3 groups, but 5-year survival was lower among those diagnosed with cancer during pregnancy or postpartum. Overall, there was a greater risk of death due to pregnancy-associated cancer among those diagnosed during pregnancy (aHR, 1.79; 95% CI, 1.51-2.13) and postpartum (aHR, 1.49; 95% CI, 1.33-1.67); however, these results varied across cancer sites. Increased hazard of mortality was observed for breast (aHR, 2.01; 95% CI, 1.58-2.56), ovarian (aHR, 2.60; 95% CI, 1.12-6.03), and stomach (aHR, 10.37; 95% CI, 3.56-30.24) cancers diagnosed during pregnancy, and brain (aHR, 2.75; 95% CI, 1.28-5.90), breast (aHR, 1.61; 95% CI, 1.32-1.95), and melanoma (aHR, 1.84; 95% CI, 1.02-3.30) cancers diagnosed postpartum.Conclusions and relevanceThis population-based cohort study found that pregnancy-associated cancers had increased overall 5-year mortality, though not all cancer sites presented the same risk.

Project description:Occult parametrial involvement in apparent early-stage cervical cancer might be overlooked with standard pathologic assessment. The primary endpoint of the present study was to assess the rate of positive parametrial lymph nodes and of microscopic continuous or discontinuous parametrial involvement. This is a retrospective, single-center, observational study including patients with FIGO 2018 stage IA1-IIA1 and IIIC1p in whom bilateral sentinel lymph node (SLN) detection and ultrastaging of SLN were performed according to institutional protocol, with surgery as primary treatment performed between May 2017 and February 2021, as well as type B2/C1/C2 (Querleu-Morrow) radical hysterectomy and usual histology (squamous cell, adenocarcinoma and adenosquamous carcinoma). Thirty-one patients were included in the study period. Six (18.7%) patients had metastatic lymph nodes, of whom four had only SLN metastasis (two cases of ITC, one case of micrometastasis and one case of macrometastasis). We found a macroscopic deposit of cancer cells in the parametrial lymph node of one patient (3.1%). There was a positive statistical correlation between the incidence of parametrial lymph node involvement and the metastatic pelvic lymph nodes (p = 0.038). When performed per patient, the sensitivity, negative predictive value and accuracy of parametrial lymph node involvement in predicting pelvic lymph node metastasis were 16.7%, 83.3% and 83.9%, respectively. Ultrastaging of parametrial tissue did not identify any occult continuous or discontinuous parametrial metastasis. In conclusion, the incidence of lymph node parametrial involvement in a retrospective series of early-stage cervical cancer was 3.1% of all included patients. Lymph node involvement of the parametrium was associated with lymph node metastasis. The sensitivity of parametrial lymph node involvement to predict pelvic lymph node metastasis was low. The lack of parametrial involvement revealed by parametrial ultrastaging could be related to the number of patients with tumors with a pathologic diameter < 2 cm (54.8%). Further prospective studies are needed to analyze the role of parametrial ultrastaging in early-stage cervical cancer and to assess whether it can be considered the "sentinel" of the sentinel lymph node.

Dataset Information

Difficulty of cervical cancer diagnosis during pregnancy: A case series analysis of the clinicopathological characteristics and prognosis of cervical cancer diagnosed during pregnancy or within 6 months after parturition.

Publications

Difficulty of cervical cancer diagnosis during pregnancy: A case series analysis of the clinicopathological characteristics and prognosis of cervical cancer diagnosed during pregnancy or within 6 months after parturition.

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