Sentinel lymph node mapping and intraoperative assessment in a prospective, international, multicentre, observational trial of patients with cervical cancer: The SENTIX trial

Background: SENTIX (ENGOT-CX2/CEEGOG-CX1) is an international, multi centre, prospective observational trial evaluating sentinel lymph node (SLN) biopsy without pelvic lymph node dissection in patients with early-stage cervical cancer. We report the final preplanned analysis of the secondary end-points: SLN mapping and outcomes of intraoperative SLN pathology. Methods: Forty-seven sites (18 countries) with experience of SLN biopsy participated in SENTIX. We preregistered patients with stage IA1/lymphovascular space invasion-positive to IB2 (4 cm or smaller or 2 cm or smaller for fertility-sparing treatment) cervical cancer without suspicious lymph nodes on imaging before surgery. SLN frozen section assessment and pathological ultrastaging were mandatory. Patients were registered postoperatively if SLN were bilaterally detected in the pelvis, and frozen sections were negative. Trial registration: ClinicalTrials.gov (NCT02494063). Results: We analysed data for 395 preregistered patients. Bilateral detection was achieved in 91% (355/395), and it was unaffected by tumour size, tumour stage or body mass index, but it was lower in older patients, in patients who underwent open surgery, and in sites with fewer cases. No SLN were found outside the seven anatomical pelvic regions. Most SLN and positive SLN were localised below the common iliac artery bifurcation. Single positive SLN above the iliac bifurcation were found in 2% of cases. Frozen sections failed to detect 54% of positive lymph nodes (pN1), including 28% of cases with macrometastases and 90% with micrometastases. Interpretation: SLN biopsy can achieve high bilateral SLN detection in patients with tumours of 4 cm or smaller. At experienced centres, all SLN were found in the pelvis, and most were located below the iliac vessel bifurcation. SLN frozen section assessment is an unreliable tool for intraoperative triage because it only detects about half of N1 cases. (C) 2020 The Author(s). Published by Elsevier Ltd

Central Pathology Review in SENTIX, a Prospective Observational International Study on Sentinel Lymph Node Biopsy in Patients with Early-Stage Cervical Cancer (ENGOT-CX2)

The quality of pathological assessment is crucial for the safety of patients with cervical cancer if pelvic lymph node dissection is to be replaced by sentinel lymph node (SLN) biopsy. Central pathology review of SLN pathological ultrastaging was conducted in the prospective SENTIX/European Network of Gynaecological Oncological Trial (ENGOT)-CX2 study. All specimens from at least two patients per site were submitted for the central review. For cases with major or critical deviations, the sites were requested to submit all samples from all additional patients for second-round assessment. From the group of 300 patients, samples from 83 cases from 37 sites were reviewed in the first round. Minor, major, critical, and no deviations were identified in 28%, 19%, 14%, and 39% of cases, respectively. Samples from 26 patients were submitted for the second-round review, with only two major deviations found. In conclusion, a high rate of major or critical deviations was identified in the first round of the central pathology review (28% of samples). This reflects a substantial heterogeneity in current practice, despite trial protocol requirements. The importance of the central review conducted prospectively at the early phase of the trial is demonstrated by a substantial improvement of SLN ultrastaging quality in the second-round review

Cervical determinants of anal HPV infection and high-grade anal lesions in women: a collaborative pooled analysis

Cervical cancer screening might contribute to the prevention of anal cancer in women. We aimed to investigate if routine cervical cancer screening results-namely high-risk human papillomavirus (HPV) infection and cytohistopathology-predict anal HPV16 infection, anal high-grade squamous intraepithelial lesions (HSIL) and, hence, anal cancer.International Agency for Research on Cance

The prevalence of anal HPV infection in women with high grade cervical intraepithelial neoplasia and its relation to sexual behavior

Background: More than 90 % of anal cancers are caused by high-risk human papillomavirus (HR HPV) infection and a history of cervical intraepithelial neoplasia (CIN) and cervical cancer is established as possible risk factor. The aim of this study was to demonstrate relationship between anal and cervical HPV infection in women with different grades of CIN and microinvasive cervical cancer and to determinate potential risk factors for concurrent cervical-anal HPV infection. Methods: A total of 272 women were enrolled in the study. The study group included 172 women who underwent conization for high-grade CIN or microinvasive cervical cancer. The control group consisted of 100 women with non-neoplastic gynecologic diseases or biopsy- confirmed CIN 1. All participants completed a questionnaire detailing their medical history and sexual risk factors and were subjected to anal and cervical HPV genotyping using Lynear array test (Roche). Results: Cervical, anal, and concurrent cervical-anal HPV infections were detected in 82.6 %, 48.3 % and 42.4 % of women in the study group, and in 28.0 %, 26.0 % and 8.0 % of women in the control group, respectively. The prevalence of the HR HPV genotypes was higher in the study group and significantly increased with the severity of cervical lesion. Concurrent infections..

The prevalence of anal HPV infection in women with high grade cervical intraepithelial neoplasia and its relation to sexual behavior

SOUHRN Úvod: Více než 90 % karcinomů anu je způsobeno infekcí vysoce rizikovými genotypy lidských papillomavirů (HR HPV). Anamnéza cervikální intraepiteliální neoplazie (CIN) a cervikálního karcinomu je proto definována jako možný rizikový faktor budoucího rozvoje karcinomu anu. Cílem práce bylo zjistit vztah mezi anální a cervikální HPV infekcí u žen s různými stupni CIN a s mikroinvazivním karcinomem děložního hrdla a určit potenciální rizikové faktory pro rozvoj společné cerviko-anální HPV infekce. Metodika: Celkem bylo do studie zahrnuto 272 žen. Studovanou skupinu zahrnovalo 172 žen, které podstoupily konizaci pro těžkou prekancerózu CIN nebo mikroinvazivní karcinom děložního hrdla (CIN 2+). Kontrolní skupina tvořilo ze 100 žen s jinými neonkologickými gynekologickými chorobami nebo s biopticky ověřenou CIN 1. Všechny účastnice vyplnily dotazník se zaměřením na anamnézu a sexuální rizikové faktory a byly jim odebrány stěry z anu a děložního hrdla na stanovení genotypu HPV pomocí testu Lynear array (Roche). Výsledky: Cervikální, anální a společná cerviko-anální HPV infekce byly zjištěny u 82,6 %, 48,3 % and 42,4 % žen ve studované skupině a u 28,0 %, 26,0 % a 8,0 % žen v kontrolní skupině. Prevalence HR HPV genotypů byla signifikantně vyšší ve studované skupině a významně narůstala se závažností...Background: More than 90 % of anal cancers are caused by high-risk human papillomavirus (HR HPV) infection and a history of cervical intraepithelial neoplasia (CIN) and cervical cancer is established as possible risk factor. The aim of this study was to demonstrate relationship between anal and cervical HPV infection in women with different grades of CIN and microinvasive cervical cancer and to determinate potential risk factors for concurrent cervical-anal HPV infection. Methods: A total of 272 women were enrolled in the study. The study group included 172 women who underwent conization for high-grade CIN or microinvasive cervical cancer. The control group consisted of 100 women with non-neoplastic gynecologic diseases or biopsy- confirmed CIN 1. All participants completed a questionnaire detailing their medical history and sexual risk factors and were subjected to anal and cervical HPV genotyping using Lynear array test (Roche). Results: Cervical, anal, and concurrent cervical-anal HPV infections were detected in 82.6 %, 48.3 % and 42.4 % of women in the study group, and in 28.0 %, 26.0 % and 8.0 % of women in the control group, respectively. The prevalence of the HR HPV genotypes was higher in the study group and significantly increased with the severity of cervical lesion. Concurrent infections...Gynekologicko-porodnická klinika 1. LF UK a VFNDepartment of Obstetrics and Gynaecology First Faculty of Medicine and General University HospitalFirst Faculty of Medicine1. lékařská fakult

The prevalence of anal HPV infection in women with high grade cervical intraepithelial neoplasia and its relation to sexual behavior

Background: More than 90 % of anal cancers are caused by high-risk human papillomavirus (HR HPV) infection and a history of cervical intraepithelial neoplasia (CIN) and cervical cancer is established as possible risk factor. The aim of this study was to demonstrate relationship between anal and cervical HPV infection in women with different grades of CIN and microinvasive cervical cancer and to determinate potential risk factors for concurrent cervical-anal HPV infection. Methods: A total of 272 women were enrolled in the study. The study group included 172 women who underwent conization for high-grade CIN or microinvasive cervical cancer. The control group consisted of 100 women with non-neoplastic gynecologic diseases or biopsy- confirmed CIN 1. All participants completed a questionnaire detailing their medical history and sexual risk factors and were subjected to anal and cervical HPV genotyping using Lynear array test (Roche). Results: Cervical, anal, and concurrent cervical-anal HPV infections were detected in 82.6 %, 48.3 % and 42.4 % of women in the study group, and in 28.0 %, 26.0 % and 8.0 % of women in the control group, respectively. The prevalence of the HR HPV genotypes was higher in the study group and significantly increased with the severity of cervical lesion. Concurrent infections..

Chlamydia trachomatis and Neisseria gonorrhoeae PCR detection in women treated for ectopic pregnancy

The aim of this study was to determine the presence of Chlamydia trachomatis (ChT) and Neisseria gonorrhoae (NG) in the genital tract of women with ectopic pregnancy and to compare the positive results with patients’ self-reported history of PID. Overall 40 women were eligible for the study. The samples for the ChT and NG Polymerase Chain-reaction (PCR) detection were obtained from the cervix, endometrium and fallopian tube. The results of testing for NG at all sites were negative as were the results from cervical testing for ChT. The prevalence of ChT in the upper genital tract was 12.5%. No statistically significant correlation was found between the positive cases and the previous signs of PID and laparoscopic findings. We found statistically significant relationship between signs of pelvic inflammation in a pacients’ history and histopathological findings of tubal inflammation. 12.5% prevalence of ChT confirms the ascending genital infection. There was no association between the positive PCR result and clinical history of pelvic inflammation.IMPACT STATEMENT What is already known on this subject? Pelvic inflammatory disease, Chlamydia trachomatis and Neisseria gonorrhoae infections are the main risks for ectopic pregnancy. Clinical history of PID and perioperative adhesions may suggest prior upper genital infection. What do the results of this study add? Chlamydia trachomatis positive PCR result can be found in the upper genital tract without the positivity of cervical smear in women with ectopic pregnancy. Our study is unique in assessing the endometrial biopsy for the presence of Chlamydia trachomatis and Neisseria gonorrhoae. What are the implications of these findings for future clinical practice and/or future clinical research? There is no statistically significant association between positive PCR result and clinical history of PID or pelvic adhesions found during laparoscopy for tubal pregnancy. Therefore there is no need for the preventive antibiotic treatment in patients with these findings

Lower-limb lymphedema after sentinel lymph node biopsy in cervical cancer patients

Background: to prospectively assess LLL incidence among cervical cancer patients treated by uterine surgery complemented by SLN biopsy, without PLND. Methods: a prospective study in 150 patients with stage IA1-IB2 cervical cancer treated by uterine surgery with bilateral SLN biopsy. Objective LLL assessments, based on limb volume increase (LVI) between pre- and postoperative measurements, and subjective patient-perceived swelling were conducted in six-month periods over 24-months post-surgery. Results: the cumulative incidence of LLL at 24 months was 17.3% for mild LLL (LVI 10-19%), 9.2% for moderate LLL (LVI 20-39%), while only one patient (0.7%) developed severe LLL (LVI > 40%). The median interval to LLL onset was nine months. Transient edema resolving without intervention within six months was reported in an additional 22% of patients. Subjective LLL was reported by 10.7% of patients, though only a weak and partial correlation between subjective-report and objective-LVI was found. No risk factor directly related to LLL development was identified. Conclusions: the replacement of standard PLND by bilateral SLN biopsy in the surgical treatment of cervical cancer does not eliminate the risk of mild to moderate LLL, which develops irrespective of the number of SLN removed

Sentinel lymph node mapping and intraoperative assessment in a prospective, international, multicentre, observational trial of patients with cervical cancer : the SENTIX trial

BACKGROUND: SENTIX (ENGOT-CX2/CEEGOG-CX1) is an international, multicentre, prospective observational trial evaluating sentinel lymph node (SLN) biopsy without pelvic lymph node dissection in patients with early-stage cervical cancer. We report the final preplanned analysis of the secondary end-points: SLN mapping and outcomes of intraoperative SLN pathology. METHODS: Forty-seven sites (18 countries) with experience of SLN biopsy participated in SENTIX. We preregistered patients with stage IA1/lymphovascular space invasion-positive to IB2 (4 cm or smaller or 2 cm or smaller for fertility-sparing treatment) cervical cancer without suspicious lymph nodes on imaging before surgery. SLN frozen section assessment and pathological ultra staging were mandatory. Patients were registered postoperatively if SLN were bilaterally detected in the pelvis, and frozen sections were negative. Trial registration: ClinicalTrials.gov (NCT02494063). RESULTS: We analysed data for 395 preregistered patients. Bilateral detection was achieved in 91% (355/395), and it was unaffected by tumour size, tumour stage or body mass index, but it was lower in older patients, in patients who underwent open surgery, and in sites with fewer cases. No SLN were found outside the seven anatomical pelvic regions. Most SLN and positive SLN were localised below the common iliac artery bifurcation. Single positive SLN above the iliac bifurcation were found in 2% of cases. Frozen sections failed to detect 54% of positive lymph nodes (pN1), including 28% of cases with macrometastases and 90% with micrometastases. INTERPRETATION: SLN biopsy can achieve high bilateral SLN detection in patients with tumours of 4 cm or smaller. At experienced centres, all SLN were found in the pelvis, and most were located below the iliac vessel bifurcation. SLN frozen section assessment is an unreliable tool for intraoperative triage because it only detects about half of N1 cases.The Czech Research Councilhttp://www.ejcancer.compm2021Obstetrics and Gynaecolog