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Detection of high-risk human papillomavirus DNA in sentinel lymph nodes of patients with cervical cancer.

ABSTRACT: The aim of the present study was to investigate the expression of human papillomavirus (HPV) DNA in sentinel lymph nodes (SLN) in patients with early-stage cervical cancer (CC). In addition, the present study compared the positive rate of SLNs metastasis detected by routine pathological examination, and investigated the value of HPV-DNA in the detection of early CC lymph node micrometastasis. Reverse transcription-quantitative PCR (RT-qPCR) was used in order to evaluate the HPV DNA detection in all CC samples [International Federation of Gynecology and Obstetrics (FIGO) stage IA2-IIA2]. The consistency of HPV-DNA was compared between primary lesions and SLNs. The positive rates of HPV-DNA were compared with pathological diagnosis of SLN metastasis, and the association between the positive expression of HPV-DNA in SLNs and the clinical and pathological parameters of patients with cervical cancer were analyzed. A total of 345 sentinel lymph nodes were detected in 100 patients with IA2-IIA2 CC. The positive rates of RT-qPCR and conventional histopathological detection of SLNs metastasis were 31.6% (109/345) and 12.8% (44/345), respectively (P<0.001). The positive expression of HPV-DNA in SLNs was associated with the clinical stage and tumor diameter (P<0.05), but not with patients' age, depth of cervical invasion, histological grade, lymphatic and vascular space invasion (LVSI), squamous cell carcinoma antigen (SCCAg) (P>0.05). The detection of HPV-DNA expression in pelvic lymph nodes of early CC may be used to improve the detection rate of micrometastasis, guide the postoperative adjuvant therapy more accurately and improve prognosis. Patients with positive HPV-DNA would require closer surveillance than those with negative HPV-DNA.

SUBMITTER: Lu Y

PROVIDER: S-EPMC7039119 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Detection of high-risk human papillomavirus DNA in sentinel lymph nodes of patients with cervical cancer.

Lu Yan Y Xu Xun X Nong Xiu-Hong XH Yao De-Sheng DS

Oncology letters 20200123 3

The aim of the present study was to investigate the expression of human papillomavirus (HPV) DNA in sentinel lymph nodes (SLN) in patients with early-stage cervical cancer (CC). In addition, the present study compared the positive rate of SLNs metastasis detected by routine pathological examination, and investigated the value of HPV-DNA in the detection of early CC lymph node micrometastasis. Reverse transcription-quantitative PCR (RT-qPCR) was used in order to evaluate the HPV DNA detection in ...[more]

PMID: 32194731

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Project description:ObjectiveDiscrepancies exist among international guidelines on the surgical staging of para-aortic lymph nodes in locally advanced cervical cancer (LACC), varying from considering a para-aortic lymph node dissection, at least up to the inferior mesenteric artery, to a complete para-aortic lymph node dissection. In this study, we aim to assess the reproducibility of our recently reported robotic technique using indocyanine green for identifying besides primary pelvic sentinel lymph nodes (SLNs), secondary para-aortic SLNs in a first case-cohort of cervical cancer patients.MethodsA retrospective case series of LACC patients with/without suspicious pelvic lymph nodes (LNs) on imaging (including two patients with an additional suspicious para-aortic LN) is reported. All patients underwent a robotic pelvic SLN and para-aortic sentinel/nonsentinel LN dissection using the da Vinci Xi platform. Indocyanine green was used as a fluorescent tracer, at a concentration of 1.9 mg/mL, and injected as 0.5 mL in each quadrant of the cervix.ResultsIn a total of 10 cases, primary pelvic SLNs (90% bilateral) with subsequent secondary para-aortic SLNs were identified in all cases. Lower para-aortic SLNs were present in all cases, and upper para-aortic SLNs were found in 9 out of 10 cases. The mean age of the cervical cancer patients was 49.8 years (SD ± 6.89), and the mean body mass index (BMI; kg/m2) was 23.96 (SD ± 4.60). The median total operative time was 105.5 min (range: 89-141 min). The mean numbers of primary pelvic SLNs and secondary lower and upper para-aortic SLNs were 3.10 (SD ± 1.10), 2.90 (SD ± 0.74), and 2.30 (SD ± 1.57), respectively. The median number of total para-aortic LNs (PALNs) dissected per patient was 11.5. Six patients had positive primary pelvic SLNs, and two had secondary positive para-aortic SLNs. The nonsentinel para-aortic LNs were negative in all cases. There were no intra- or postoperative complications.ConclusionOur preliminary experience demonstrates the reproducibility of identifying, besides primary pelvic SLNs, secondary lower and upper para-aortic SLNs during robotic staging in LACC. A surgical approach limiting a complete para-aortic LN dissection could reduce the potential risks and morbidity associated with this procedure. To determine the sensitivity and negative predictive value of this new surgical approach, and whether the lower para-aortic SLNs under the inferior mesenteric artery are representative of the whole para-aortic region, large prospective observational studies are needed in LACC and/or those with suspicious pelvic LNs but apparent normal para-aortic LNs on imaging.

Project description:ObjectiveTo provide the first report on the main outcomes from the prevalence and incidence rounds of a large pilot of routine primary high risk human papillomavirus (hrHPV) testing in England, compared with contemporaneous primary liquid based cytology screening.DesignObservational study.SettingThe English Cervical Screening Programme.Participants578 547 women undergoing cervical screening in primary care between May 2013 and December 2014, with follow-up until May 2017; 183 970 (32%) were screened with hrHPV testing.InterventionsRoutine cervical screening with hrHPV testing with liquid based cytology triage and two early recalls for women who were hrHPV positive and cytology negative, following the national screening age and interval recommendations.Main outcome measuresFrequency of referral for a colposcopy; adherence to early recall; and relative detection of cervical intraepithelial neoplasia grade 2 or worse from hrHPV testing compared with liquid based cytology in two consecutive screening rounds.ResultsBaseline hrHPV testing and early recall required approximately 80% more colposcopies, (adjusted odds ratio 1.77, 95% confidence interval 1.73 to 1.82), but detected substantially more cervical intraepithelial neoplasia than liquid based cytology (1.49 for cervical intraepithelial neoplasia grade 2 or worse, 1.43 to 1.55; 1.44 for cervical intraepithelial neoplasia grade 3 or worse, 1.36 to 1.51) and for cervical cancer (1.27, 0.99 to 1.63). Attendance at early recall and colposcopy referral were 80% and 95%, respectively. At the incidence screen, the 33 506 women screened with hrHPV testing had substantially less cervical intraepithelial neoplasia grade 3 or worse than the 77 017 women screened with liquid based cytology (0.14, 0.09 to 0.23).ConclusionsIn England, routine primary hrHPV screening increased the detection of cervical intraepithelial neoplasia grade 3 or worse and cervical cancer by approximately 40% and 30%, respectively, compared with liquid based cytology. The very low incidence of cervical intraepithelial neoplasia grade 3 or worse after three years supports extending the screening interval.

Project description:BackgroundAccurate identification of sentinel lymph nodes in patients with cancer improves detection of metastatic disease and decreases surgical morbidity. We sought to establish whether indocyanine green fluorescent dye is non-inferior to isosulfan blue dye in detecting sentinel lymph nodes in women with cervical and uterine cancers.MethodsIn this non-inferiority, within-patient comparison study, patients aged 18 years or older with clinical stage I endometrial or cervical cancer undergoing curative surgery were randomly assigned 1:1 to lymphatic mapping with isosulfan blue dye (visualised by white light) followed by indocyanine green (visualised by near-infrared imaging), or indocyanine green followed by isosulfan blue dye. Permuted block randomisation with stratification by study site was done with a computerised random number generator. All participants were masked to their randomisation assignment until after the procedure; however, investigators were not masked to the procedure used. Laparoscopic surgery with the PINPOINT near-infrared fluorescence imaging system (Stryker, Kalamazoo, MI, USA) was used in all cases. The primary outcome was efficacy of intraoperative indocyanine green with near-infrared fluorescence imaging versus that of isosulfan blue dye in the identification of lymph nodes, defined as the number of lymph nodes identified by indocyanine green and isosulfan blue dye, respectively (and confirmed as lymphoid tissue by histology), divided by the number of lymph nodes identified intraoperatively and excised. The study had a 5% non-inferiority margin needed to show non-inferiority of the frequency of lymph node detection with indocyanine green to that with isosulfan blue dye with 80% power at a 5% two-sided significance level. Analyses were done in both per-protocol and modified intention-to-treat populations. The trial was registered with ClinicalTrials.gov, number NCT02209532, and is completed and closed.FindingsBetween Dec 21, 2015, and June 19, 2017, 180 patients were enrolled and randomly assigned to the two groups (90 to each group); 176 patients received the intervention and were evaluable (modified intention-to-treat population). 13 patients with major protocol violations were subsequently excluded from the per-protocol population. 517 sentinel nodes were identified in the per-protocol population (n=163), of which 478 (92%) were confirmed to be lymph nodes on pathological processing: 219 (92%) of 238 nodes that were both blue and green, all seven nodes that were blue only, and 252 (95%) of 265 nodes that were green only (p=0·33). Seven sentinel lymph nodes were neither blue nor green but were removed for appearing suspicious or enlarged on visual examination. In total, 471 (97%) of 485 lymph nodes were identified with the green dye and 226 (47%) with the blue dye (difference 50%, 95% CI 39-62; p<0·0001). In the modified intention-to-treat population (n=176), 545 nodes were identified, of which 513 (94%) were confirmed to be lymph nodes on pathological processing: 229 (92%) of 248 nodes that were both blue and green, all nine nodes that were blue only, and 266 (95%) of 279 nodes that were green only (p=0·30). Nine sentinal lymph nodes were neither blue nor green but were removed for appearing suspicious or enlarged on visual examination. 495 (96%) of 513 nodes were identified with the green dye and 238 (46%) with the blue dye (50%, 39-61; p<0·0001).InterpretationIndocyanine green dye with near-infrared fluorescence imaging identified more sentinel nodes than isosulfan blue dye in women with cervical and uterine cancers, with no difference in the pathological confirmation of nodal tissue between the two mapping substances.FundingNovadaq.

Project description:BackgroundSentinel lymph node spread is a crucial factor in melanoma outcome. We aimed to define the impact of minimal cancer spread and of increasing numbers of disseminated cancer cells on melanoma-specific survival.Methods and findingsWe analyzed 1,834 sentinel nodes from 1,027 patients with ultrasound node-negative melanoma who underwent sentinel node biopsy between February 8, 2000, and June 19, 2008, by histopathology including immunohistochemistry and quantitative immunocytology. For immunocytology we recorded the number of disseminated cancer cells (DCCs) per million lymph node cells (DCC density [DCCD]) after disaggregation and immunostaining for the melanocytic marker gp100. None of the control lymph nodes from non-melanoma patients (n?=?52) harbored gp100-positive cells. We analyzed gp100-positive cells from melanoma patients by comparative genomic hybridization and found, in 45 of 46 patients tested, gp100-positive cells displaying genomic alterations. At a median follow-up of 49 mo (range 3-123 mo), 138 patients (13.4%) had died from melanoma. Increased DCCD was associated with increased risk for death due to melanoma (univariable analysis; p<0.001; hazard ratio 1.81, 95% CI 1.61-2.01, for a 10-fold increase in DCCD + 1). Even patients with a positive DCCD ?3 had an increased risk of dying from melanoma compared to patients with DCCD?=?0 (p?=?0.04; hazard ratio 1.63, 95% CI 1.02-2.58). Upon multivariable testing DCCD was a stronger predictor of death than histopathology. The final model included thickness, DCCD, and ulceration (all p<0.001) as the most relevant prognostic factors, was internally validated by bootstrapping, and provided superior survival prediction compared to the current American Joint Committee on Cancer staging categories.ConclusionsCancer cell dissemination to the sentinel node is a quantitative risk factor for melanoma death. A model based on the combined quantitative effects of DCCD, tumor thickness, and ulceration predicted outcome best, particularly at longer follow-up. If these results are validated in an independent study, establishing quantitative immunocytology in histopathological laboratories may be useful clinically.

Dataset Information

Detection of high-risk human papillomavirus DNA in sentinel lymph nodes of patients with cervical cancer.

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Detection of high-risk human papillomavirus DNA in sentinel lymph nodes of patients with cervical cancer.

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