The detection of HPV infection and microbial colonization in cervical lesions is currently done through PCR-based viral or bacterial DNA amplification. Our objective was to develop a methodology to expand the metaproteomic landscape of cervical disease and determine if protein biomarkers from both human and microbes could be detected in distinct cervical samples. This would lead to the development of multi-species proteomics, which includes protein-based lateral flow diagnostics that can define patterns of microbes and/or human proteins relevant to disease status. In this study, we collected both non-frozen tissue biopsy and exfoliative non-fixed cytology samples to assess the consistency of detecting human proteomic signatures between the cytology and biopsy samples. Our results show that proteomics using biopsies or cytologies can detect both human and microbial organisms. Across patients, Lumican and Galectin-1 were most highly expressed human proteins in the tissue biopsy, whilst IL-36 and IL-1RA were most highly expressed human proteins in the cytology. We also used mass spectrometry to assess microbial proteomes known to reside based on prior 16S rRNA gene signatures. Lactobacillus spp. was the most highly expressed proteome in patient samples and specific abundant Lactobacillus proteins were identified. These methodological approaches can be used in future metaproteomic clinical studies to interrogate the vaginal human and microbiome structure and metabolic diversity in cytologies or biopsies from the same patients who have pre-invasive cervical intraepithelial neoplasia, invasive cervical cancer, as well as in healthy controls to assess how human and pathogenic proteins may correlate with disease presence and severity.

• MeSH
• biologické markery * analýza   metabolismus   MeSH
• biopsie MeSH
• cervix uteri * mikrobiologie   patologie   MeSH
• dospělí MeSH
• galektin 1 metabolismus   analýza   genetika   MeSH
• Lactobacillus MeSH
• lidé MeSH
• lumican MeSH
• mikrobiota MeSH
• nádory děložního čípku patologie   mikrobiologie   MeSH
• proteomika * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery * MeSH
• galektin 1 MeSH
• lumican MeSH

Occult cervical cancer is rare and is diagnosed incidentally after a simple hysterectomy. The staging upon histological examination is usually International Federation of Gynecology and Obstetrics (FIGO) stage I, rarely higher with negative preoperative diagnostic tests such as a Pap smear. The clinical case in question is a rare case of cervical carcinoma diagnosed at the time of hysterectomy with a negative exo-endocervical Pap smear, diagnostic tests including transvaginal ultrasound, abdominal magnetic resonance imaging and abdominal computed tomography with a diagnosis of degenerating myoma or suspected sarcoma. In the operating theatre, the surgical radicality was modified and the operation was completed with removal of the parameters, vaginal collar and bilateral pelvic lymphadenectomy. The final histological examination indicated FIGO stage III, for which the patient underwent radiotherapy and chemotherapy.

• Klíčová slova
• FIGO classification, computed tomography, magnetic resonance, magnetic resonance imaging, occult carcinoma of the cervix, pathology,
• MeSH
• cervix uteri patologie   MeSH
• hysterektomie metody   MeSH
• lidé MeSH
• nádory děložního čípku * diagnóza   terapie   patologie   MeSH
• Papanicolaouův test MeSH
• retrospektivní studie MeSH
• staging nádorů MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH

INTRODUCTION: The standard procedure in cervical cancer is radical hysterectomy and pelvic lymphadenectomy (PLND). Because of the increasing age of women bearing children, fertility has become a major challenge. We present pregnancy results after less radical fertility-sparing surgery in women with IA1, LVSI positive, IA2 and IB1 (<2 cm, infiltration less than half of the cervical stroma). MATERIALS AND METHOD: All women (n = 91) underwent laparoscopic sentinel lymph node mapping with frozen section followed by PLND and "selective parametrectomy" (removal of afferent lymphatic channels from the paracervix) if sentinel nodes (SLN) are negative. If lymph nodes were verified negative by definitive histopathology, patients were treated by simple trachelectomy (IB1) or large cone (IA1/IA2) biopsy 1 week after primary surgery. RESULTS: From 1999 to 2018, 91 women were enrolled in the study (median age 29.1 years, range 21-40). Fertility was spared in 76 (83.5%) women; 13 (17.1%) women did not plan future pregnancy and 63 (82.9%) had pregnancy desires. Fifty-four of 63 women conceived (pregnancy rate 85.7%) and 48 of 63 delivered 58 babies (delivery rate 76.2%). Thirty-nine women delivered in term (67.2%): 13 women between 32 and 36 + 6 weeks of pregnancy, 3 between 28 and 31 + 6 weeks and 3 between 24 and 27 + 6 weeks. Only one woman still plans pregnancy. One woman is currently pregnant. CONCLUSION: The goal of fertility-sparing surgery is to produce good oncological results and promising pregnancy outcomes. Pregnancy results after less radical fertility-sparing procedures show promise (pregnancy rate 82.9% and delivery rate 76.2%).

• Klíčová slova
• Cervical cancer, Less radical fertility-sparing surgery, Pregnancy outcomes, Sentinel lymph node mapping,
• MeSH
• biopsie sentinelové lymfatické uzliny MeSH
• cerkláž cervikální MeSH
• cervix uteri * patologie   chirurgie   MeSH
• dospělí MeSH
• fertilita * fyziologie   MeSH
• laparoskopie MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádory děložního čípku * diagnóza   patologie   chirurgie   MeSH
• peritoneum chirurgie   MeSH
• předčasný porod epidemiologie   MeSH
• těhotenství MeSH
• trachelektomie MeSH
• výsledek těhotenství * MeSH
• zachování plodnosti * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Fertility-sparing treatment in patients with cervical cancer should, in principle, follow identical algorithms to that in patients without future reproductive plans. In recent years, a trend toward nonradical procedures, such as conization or simple trachelectomy, has become apparent in medical literature, because of their associations with better pregnancy outcomes. However, the published reports included small numbers of patients and heterogenous treatment strategies to ascertain the safety of such approaches. OBJECTIVE: This study aimed to collect multi-institutional data regarding the oncological outcomes after fertility-sparing treatment in patients with cervical cancer and to identify prognostic risk factors, including the influence of the radicality of individual cervical procedures. STUDY DESIGN: Patients aged 18 to 40 years with International Federation of Gynecology and Obstetrics 2018 stage IA1 with positive lymphovascular space invasion or ≥IA2 cervical cancer who underwent any type of fertility-sparing procedure were eligible for this retrospective observational study, regardless of their histotype, tumor grade, and history of neoadjuvant chemotherapy. Associations between disease- and treatment-related characteristics with the risk of recurrence were analyzed. RESULTS: A total of 733 patients from 44 institutions across 13 countries were included in this study. Almost half of the patients had stage IB1 cervical cancer (49%), and two-thirds of patients were nulliparous (66%). After a median follow-up of 72 months, 51 patients (7%) experienced recurrence, of whom 19 (2.6%) died because of the disease. The most common sites of recurrence were the cervix (53%) and pelvic nodes (22%). The risk of recurrence was 3 times higher in patients with tumors >2 cm in size than in patients with smaller tumors, irrespective of the treatment radicality (19.4% vs 5.7%; hazard ratio, 2.982; 95% confidence interval, 1.383-6.431; P=.005). The recurrence risk in patients with tumors ≤2 cm in size did not differ between patients who underwent radical trachelectomy and patients who underwent nonradical (conization and simple trachelectomy) cervical procedures (P=.957), regardless of tumor size subcategory (<1 or 1-2 cm) or lymphovascular space invasion. CONCLUSION: Nonradical fertility-sparing cervical procedures were not associated with an increased risk of recurrence compared with radical procedures in patients with tumors ≤2 cm in size in this large, multicenter retrospective study. The risk of recurrence after any type of fertility-sparing procedure was significantly greater in patients with tumors >2 cm in size.

• Klíčová slova
• cervical cancer, conization, fertility-sparing treatment, recurrence, trachelectomy,
• MeSH
• cervix uteri chirurgie   patologie   MeSH
• lidé MeSH
• nádory děložního čípku * chirurgie   patologie   MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• staging nádorů MeSH
• těhotenství MeSH
• výsledek těhotenství MeSH
• zachování plodnosti * metody   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Uterus transplantation is a causal treatment for absolute uterine factor infertility. Assessing rejection signs using a histopathological examination of the ectocervical biopsy from the transplanted uterus is common practice in all human uterus transplants worldwide to date. A provisional scoring system was used for the histopathological assessment of subclinical rejection signs in uterus recipients. Here we hypothesized that histopathological and immunohistochemical findings in the normal uteri would differ from the borderline category of subclinical rejection in uterine transplants. MATERIAL AND METHODS: This prospective observational study included ectocervical biopsies of 54 women who underwent hysterectomy for benign reasons. All biopsy samples were assessed histopathologically and immunohistochemically. RESULTS: Most of the ectocervical biopsies showed clustering lymphocytic infiltrates affecting the stromal-epithelial interface with the epithelial influx of lymphocytes, primarily CD45RO-positive activated T-cells with CD8 T-lymphocyte predominance. CD4-positive T-lymphocytes and B-cells were rarely detected in the ectocervix. These morphological findings and immunoprofiles of lymphocytic populations overlapped with the so-called borderline changes defined in the provisional scoring system for rejection in the transplanted uteri. The immunoprofiles of ectocervical and endocervical lymphocytic populations differed, with strikingly prominent B-cell participation in the endocervix vs the rare detection of B-cells in the ectocervix. CONCLUSIONS: The histopathological and immunohistochemical findings in the uteri of premenopausal women were similar to the borderline category of the currently used provisional scoring system of subclinical uterine rejection utilized in all uterine transplant studies. However, future similar studies are required to validate our findings.

• Klíčová slova
• cervical biopsy, histopathology, hysterectomy, immunohistochemistry, organ rejection, uterus transplantation,
• MeSH
• biopsie MeSH
• cervix uteri patologie   MeSH
• dospělí MeSH
• hysterektomie MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• rejekce štěpu patologie   MeSH
• uterus transplantace   MeSH
• výzkumný projekt MeSH
• ženská infertilita chirurgie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

BACKGROUND: Squamous cell carcinoma is the most common malignant tumor of the uterine cervix with a well-documented link to infection with human papillomaviruses (HPV). According to a recent classification, there are several morphological variants of cervical squamous carcinoma, without reference to sarcomatoid squamous cell carcinoma, which is well described in other organs. CASE PRESENTATION: In this paper, we describe an extremely rare case of a 77-year-old woman with primary malignant cervical tumor displaying biphasic histomorphology with an epithelioid and sarcomatoid part; the latter was immunohistochemistry positive for cytokeratin and vimentin. The association with a high-grade squamous intraepithelial lesion and molecular proof of HPV33 infection in the tumor tissue supported our diagnosis of carcinoma with partial sarcomatoid differentiation. CONCLUSION: We report a rare case of a primary cervical epithelial tumor with a partial sarcomatoid phenotype, an unequivocal HPV infection, and an associated precancerous lesion in the cervical mucosa. This is the first description of an HPV33 infection underlying a biphasic epithelioid-sarcomatous tumor of the uterine cervix. The terminology overlap between sarcomatoid carcinoma and carcinosarcoma is also discussed.

• Klíčová slova
• Carcinsarcoma, Cervix, HPV, Sarcomatoid, Squamous carcinoma,
• MeSH
• buněčná diferenciace fyziologie   MeSH
• cervix uteri patologie   virologie   MeSH
• infekce papilomavirem virologie   MeSH
• karcinosarkom komplikace   diagnóza   patologie   MeSH
• keratiny metabolismus   MeSH
• lidé MeSH
• nádory děložního čípku diagnóza   patologie   MeSH
• sarkom patologie   virologie   MeSH
• senioři MeSH
• spinocelulární karcinom komplikace   diagnóza   patologie   MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• keratiny MeSH

INTRODUCTION: The carcinoma of the cervix uteri is the fourth most common cancer in women worldwide and more than 85% of these cases occur in developing countries. Altogether 822 new cases were found in the Czech Republic during 2016 which means the incidence 15,3 new diseases/100,000 women. OBJECTIVE: To provide an overview of changes in FIGO (International Federation of Gynecology and Obstetrics) staging for carcinoma of the cervix uteri with an incorporation of possible imaging methods and/or pathological findings, and clinical assessment of tumor size and extent. SETTINGS: Gynecologic Oncology Center, Department of Gynecology and Obstetrics, Hospital Na Bulovce and 1st Medical School of Charles University, Prague; Gynecologic Oncology Center, Department of Gynecology and Obstetrics, General Faculty Hospital and 1st Medical School of Charles University, Prague; Institute of Radiation Oncology, Hospital Na Bulovce, Prague. METHODS: For this review, we have used the results of studies, review articles, and guidelines of oncogynecologic organisations on the cervical cancer published in English. They were identified through a search of literature using PubMed, MEDLINE-Ovid, Scopus and Cochrane Library with the keywords. We summarize the new classification, main changes compared to the former one and their clinical impact. CONCLUSION: Lateral extension measurement is removed in the stage IA, the only criterion is the measured deepest invasion.

• Klíčová slova
• ESGO, FIGO, carcinoma, cervix uteri, staging,
• MeSH
• cervix uteri patologie   MeSH
• gynekologie MeSH
• karcinom diagnostické zobrazování   patologie   MeSH
• lidé MeSH
• lymfatické metastázy diagnostické zobrazování   patologie   MeSH
• nádory děložního čípku diagnostické zobrazování   patologie   MeSH
• staging nádorů trendy   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: DNA methylation has been suggested as one of the epigenetic changes promoting carcinogenesis. The aim of this study was to prospectively evaluate the methylation status of CADM 1, MAL and hsa-miR-124 genes in high-grade squamous intraepithelial lesion (HSIL) liquid-based cytology (LBC) samples with a histological correlation. METHODS: Seventy histologically confirmed cases of HSIL paired with prior screening LBC diagnosis of HSIL within a 3-month interval were selected. Histologically, the lesions were reviewed and assessed including: (a) number of blocks harbouring dysplastic squamous epithelium; (b) number of blocks containing glandular extension of dysplastic epithelium; and (c) the depth of glandular extension (which was assessed semi-quantitatively as graded 1-3). Human papillomavirus (HPV) subtyping was performed from residual LBC materials using the LINEAR ARRAY HPV Genotyping Test and in-house polymerase chain reaction targeting the HPV E1 gene. The detection of methylation silencing of tumour suppressor genes CADM1, MAL and hsa-miR-124 was performed by multiplex methylation-specific real-time polymerase chain reaction. RESULTS: A positive methylation status was detected in 41 cases (58.6%). The number of blocks with HSIL varied from one to 13. Glandular extension was seen in 44 cases with the number of blocks involved ranging from one to 10. The depth of HSIL glandular extension varied. CONCLUSION: The DNA methylation test allows HSIL lesions to be divided into two distinct groups of methylated HSIL in significantly older patients and unmethylated HSIL in younger patients. This study was not able to prove that methylation status in cervical HSIL correlates with the size of the lesion (measured by the number of blocks involved) or with HSIL propensity for endocervical glandular extension, nor with HPV type or multi-infection.

• Klíčová slova
• HSIL, cervix, cytology, hypermethylation, methylation,
• MeSH
• buněčná adhezní molekula 1 genetika   MeSH
• cervix uteri patologie   virologie   MeSH
• cytodiagnostika * MeSH
• dlaždicová intraepiteliální léze cervixu diagnóza   genetika   patologie   virologie   MeSH
• dospělí MeSH
• genotypizační techniky MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA genetika   MeSH
• mikro RNA genetika   MeSH
• mladý dospělý MeSH
• nádorové supresorové proteiny genetika   MeSH
• Papanicolaouův test MeSH
• Papillomaviridae patogenita   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• skvamózní intraepiteliální léze diagnóza   genetika   patologie   virologie   MeSH
• vaginální stěr MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• buněčná adhezní molekula 1 MeSH
• CADM1 protein, human MeSH Prohlížeč
• mikro RNA MeSH
• MIRN124 microRNA, human MeSH Prohlížeč
• nádorové supresorové proteiny MeSH

Radiotherapy is an important therapeutic approach against cervical cancer but associated with adverse effects including vaginal fibrosis and dyspareunia. We here assessed the immunological and oxidative responses to cervical irradiation in an animal model for radiation-induced cervicitis. Rats were sedated and either exposed to 20 Gy of ionising radiation given by a linear accelerator or only sedated (controls) and euthanized 1-14 days later. The expressions of toll-like receptors (TLRs) and coupled intracellular pathways in the cervix were assessed with immunohistofluorescence and western blot. Expression of cytokines were analysed with the Bio-Plex Suspension Array System (Bio-Rad). We showed that TLRs 2-9 were expressed in the rat cervix and cervical irradiation induced up-regulation of TLR5, TRIF and NF-κB. In the irradiated cervical epithelium, TLR5 and TRIF were increased in concert with an up-regulation of oxidative stress (8-OHdG) and antioxidant enzymes (SOD-1 and catalase). G-CSF, M-CSF, IL-10, IL- 17A, IL-18 and RANTES expressions in the cervix decreased two weeks after cervical irradiation. In conclusion, the rat uterine cervix expresses the TLRs 2-9. Cervical irradiation induces immunological changes and oxidative stress, which could have importance in the development of adverse effects to radiotherapy.

• MeSH
• adaptorové proteiny vezikulární transportní imunologie   MeSH
• cervix uteri imunologie   patologie   MeSH
• cytokiny imunologie   MeSH
• experimentální radiační poranění imunologie   patologie   MeSH
• krysa rodu Rattus MeSH
• NF-kappa B imunologie   MeSH
• oxidační stres imunologie   účinky záření   MeSH
• potkani Sprague-Dawley MeSH
• regulace genové exprese imunologie   účinky záření   MeSH
• toll-like receptory imunologie   MeSH
• zánět děložního hrdla imunologie   patologie   MeSH
• záření gama škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adaptorové proteiny vezikulární transportní MeSH
• cytokiny MeSH
• NF-kappa B MeSH
• Ticam1 protein, rat MeSH Prohlížeč
• toll-like receptory MeSH

Currently, three prophylactic HPV vaccines are commercially available to prevent HPV 16/18 infection and associated lesions. The aim of the study was to assess markers of HPV infection in women/girls before vaccination and to ascertain the prevalence and spectrum of post-vaccination HPV types. Three hundred and thirty subjects of which 75 were virgins were enrolled. Before the first dose of the HPV vaccine and 1, 3 and 5 years after the completion of HPV vaccination, the samples for cytology, HPV detection and anti-HPV antibody response were taken. At enrolment, HPV DNA was detected in 38% of sexually active girls/women. At the first, second and third follow-up, HPV DNA was found in 40, 45, and 39% of them. The seroprevalence rates to HPV 6, 11, 16 and 18 in these subjects were 31, 21, 18 and 10%. On the follow-up significantly higher levels of antibodies to HPV 16/18 were found after application of divalent vaccine. Results of the study demonstrate high prevalence of HPV infection in young women. In a substantial number of women, HPV-specific antibodies as well as high-risk HPV types were detected. HPV-specific antibodies were also frequently found in non-sexually active girls. The acquisition of HPV after the onset of sexual life was very fast.

• Klíčová slova
• DNA, HPV, antibodies, infection, persistence, vaccination,
• MeSH
• cervix uteri patologie   virologie   MeSH
• DNA virů analýza   MeSH
• dospělí MeSH
• infekce papilomavirem epidemiologie   prevence a kontrola   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Papillomaviridae izolace a purifikace   MeSH
• protilátky virové krev   MeSH
• séroepidemiologické studie MeSH
• vakcíny proti papilomavirům aplikace a dávkování   imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA virů MeSH
• protilátky virové MeSH
• vakcíny proti papilomavirům MeSH