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Simple Summary: Constant technological development of modern imaging has led to substantial improvement in management and decision-making in the diagnostic and prognostic process of many different neoplasms. This also applies to cervical cancer. The main evidence, providing the base of recently updated ESGO-ESTRO-ESP recommendations (2023) on the management and treatment of cervical cancer, has been evaluated and reviewed in this paper. Ultrasound has been suggested as a valid alternative to MRI in primary diagnostic workup of cervical cancer if performed by an expert sonographer. Additionally, CT or PET/CT exhibits a substantial role in assessing the extrapelvic spread of the disease in locally advanced cases or when suspicious lymph nodes are detected. The purpose of this article is to provide a comprehensive review of the role of different imaging techniques in staging settings, displaying a focused interest in the use of ultrasound. Following the European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) joint guidelines (2018) for the management of patients with cervical cancer, treatment decisions should be guided by modern imaging techniques. After five years (2023), an update of the ESGO-ESTRO-ESP recommendations was performed, further confirming this statement. Transvaginal/transrectal ultrasound (TRS/TVS) or pelvic magnetic resonance (MRI) enables tumor delineation and precise assessment of its local extent, including the evaluation of the depth of infiltration in the bladder- or rectal wall. Additionally, both techniques have very high specificity to confirm the presence of metastatic pelvic lymph nodes but fail to exclude them due to insufficient sensitivity to detect small-volume metastases, as in any other currently available imaging modality. In early-stage disease (T1a to T2a1, except T1b3) with negative lymph nodes on TVS/TRS or MRI, surgicopathological staging should be performed. In all other situations, contrast-enhanced computed tomography (CECT) or 18F-fluorodeoxyglucose positron emission tomography combined with CT (PET-CT) is recommended to assess extrapelvic spread. This paper aims to review the evidence supporting the implementation of diagnostic imaging with a focus on ultrasound at primary diagnostic workup of cervical cancer. [ABSTRACT FROM AUTHOR]

Context.--Ultrastaging of sentinel lymph nodes (SLNs) is a crucial aspect in the approach to SLN processing. No consensual protocol for pathologic ultrastaging has been approved by international societies to date. Objective.--To provide a review of the ultrastaging protocol and all its aspects related to the processing of SLNs in patients with cervical cancer. Data Sources.--In total, 127 publications reporting data from 9085 cases were identified in the literature. In 24% of studies, the information about SLN processing is entirely missing. No ultrastaging protocol was used in 7% of publications. When described, the differences in all aspects of SLN processing among the studies and institutions are substantial. This includes grossing of the SLN, which is not completely sliced and processed in almost 20% of studies. The reported protocols varied in all aspects of SLN processing, including the thickness of slices (range, 1-5 mm), the number of levels (range, 0-cut out until no tissue left), distance between the levels (range, 40-1000 im), and number of sections per level (range, 1-5). Conclusions.--We found substantial differences in protocols used for SLN pathologic ultrastaging, which can impact sensitivity for detection of micrometastases and even small macrometastases. Since the involvement of pelvic lymph nodes is the most important negative prognostic factor, such profound discrepancies influence the referral of patients to adjuvant radiotherapy and could potentially cause treatment failure. It is urgent that international societies agree on a consensual protocol before SLN biopsy without pelvic lymphadenectomy is introduced into routine clinical practice. doi: 10.5858/arpa.2019-0249-RA, During the last few years, sentinel lymph node (SLN) biopsy has emerged as one of the most promising and effective approaches for patients with early-stage cervical cancer. (1-3) According to [...]

The article focuses on the threshold for radical hysterectomy in the treatment of low-risk cervical cancer, currently between stages T1a2 and T1b1, and the criteria proposed in the SHAPE trial by Plante et al. that advocate for a simpler hysterectomy approach for tumors up to 2 cm in size combined with limited stromal invasion.

The majority of endometrial and cervical cancers present with abnormal vaginal bleeding but only a small proportion of women suffering from vaginal bleeding actually have such a cancer. A simple, operator‐independent and accurate test to correctly identify women presenting with abnormal bleeding as a consequence of endometrial or cervical cancer is urgently required. We have recently developed and validated the WID‐qEC test, which assesses DNA methylation of ZSCAN12 and GYPC via real‐time PCR, to triage women with symptoms suggestive of endometrial cancer using ThinPrep‐based liquid cytology samples. Here, we investigated whether the WID‐qEC test can additionally identify women with cervical cancer. Moreover, we evaluate the test's applicability in a SurePath‐based hospital‐cohort by comparing its ability to detect endometrial and cervical cancer to cytology. In a set of 23 cervical cancer cases and 28 matched controls the receiver operating characteristic (ROC) area under the curve (AUC) is 0.99 (95% confidence interval [CI]: 0.97‐1.00) with a sensitivity and specificity of 100% and 92.9%, respectively. Amongst the hospital‐cohort (n = 330), the ROC AUC is 0.99 (95% CI: 0.98‐1) with a sensitivity and specificity of 100% and 82.5% for the WID‐qEC test, respectively, and 33.3% and 96.9% for cytology (considering PAP IV/V as positive). Our data suggest that the WID‐qEC test detects both endometrial and cervical cancer with high accuracy. [ABSTRACT FROM AUTHOR]

Background: Cervical screening using primary human papilloma virus (HPV) testing and cytology is being implemented in several countries. Cytology as triage for colposcopy referral suffers from several shortcomings. HPV testing overcomes some of these but lacks specificity in women under 30. Here, we aimed to develop and validate an automatable triage test that is highly sensitive and specific independently of age and sample heterogeneity, and predicts progression to CIN3+ in HPV+ patients. Results: The WID™-qCIN, assessing three regions in human genes DPP6, RALYL, and GSX1, was validated in both a diagnostic (case–control) and predictive setting (nested case–control), in a total of 761 samples. Using a predefined threshold, the sensitivity of the WID™-qCIN test was 100% and 78% to detect invasive cancer and CIN3, respectively. Sensitivity to detect CIN3+ was 65% and 83% for women < and ≥ 30 years of age. The specificity was 90%. Importantly, the WID™-qCIN test identified 52% of ≥ 30-year-old women with a cytology negative (cyt−) index sample who were diagnosed with CIN3 1–4 years after sample donation. Conclusion: We identified suitable DNAme regions in an epigenome-wide discovery using HPV+ controls and CIN3+ cases and established the WID™-qCIN, a PCR-based DNAme test. The WID™-qCIN test has a high sensitivity and specificity that may outperform conventional cervical triage tests and can in an objective, cheap, and scalable fashion identify most women with and at risk of (pre-)invasive cervical cancer. However, evaluation was limited to case–control settings and future studies will assess performance and generalisability in a randomised controlled trial. [ABSTRACT FROM AUTHOR]

Up to 26% of patients with early-stage cervical cancer experience relapse after primary surgery. However, little is known about which factors influence prognosis following disease recurrence. Therefore, our aims were to determine post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors for PR-DSS. Data from 528 patients with early-stage cervical cancer who relapsed after primary surgery performed between 2007 and 2016 were obtained from the SCANN study (Surveillance in Cervical CANcer). Factors related to the primary disease and recurrence were combined in a multivariable Cox proportional hazards model to predict PR-DSS. The 5-year PR-DSS was 39.1% (95% confidence interval [CI] 22.7%–44.5%), median disease-free interval between primary surgery and recurrence (DFI1) was 1.5 years, and median survival after recurrence was 2.5 years. Six significant variables were identified in the multivariable analysis and were used to construct the prognostic model. Two were related to primary treatment (largest tumour size and lymphovascular space invasion) and four to recurrence (DFI1, age at recurrence, presence of symptoms, and recurrence type). The C-statistic after 10-fold cross-validation of prognostic model reached 0.701 (95% CI 0.675–0.727). Three risk-groups with significantly differing prognoses were identified, with 5-year PR-DSS rates of 81.8%, 44.6%, and 12.7%. We developed the robust model of PR-DSS to stratify patients with relapsed cervical cancer according to risk profiles using six routinely recorded prognostic markers. The model can be utilised in clinical practice to aid decision-making on the strategy of recurrence management, and to better inform the patients. • The 5-year post-recurrence disease-specific survival (PR-DSS) rate was 39.1% in patients with early-stage cervical cancer. • The strongest factors for PR-DSS were primary tumour size and the presence of symptoms at diagnosis of recurrence. • The presence of symptoms at recurrence remained a significant prognostic factor after correction for lead-time bias. • PR-DSS was best in patients without LN involvement or LVSI suffering from solitary asymptomatic recurrence. [ABSTRACT FROM AUTHOR]

The anatomic descriptions and extents of radical hysterectomy often vary across the literature and operative reports worldwide. The same nomenclature is often used to describe varying procedures, and different nomenclature is often used to describe the same procedure despite the availability of guideline and classification systems. This makes it difficult to interpret retrospective surgical reports, analyze surgical databases, understand technique descriptions, and interpret the findings of surgical studies. In collaboration with international experts in gynecologic oncology, the purpose of this study was to establish a consensus in defining and interpreting the 2017 updated Querleu-Morrow classification of radical hysterectomies. The anatomic templates of type A, B, and C radical hysterectomy were documented through a set of 13 images taken at the time of cadaver dissection. An online survey related to radical hysterectomy nomenclature and definitions or descriptions of the associated procedures was circulated among international experts in radical hysterectomy. A 3-step modified Delphi method was used to establish consensus. Image legends were amended according to the experts' responses and then redistributed as part of a second round of the survey. Consensus was defined by a yes response to a question concerning a specific image. Anyone who responded no to a question was welcome to comment and provide justification. A final set of images and legends were compiled to anatomically illustrate and define or describe a lateral, ventral, and dorsal excision of the tissues surrounding the cervix. In total, there were 13 questions to review, and 29 experts completed the whole process. Final consensus exceeded 90% for all questions except 1 (86%). Questions with relatively lower consensus rates concerned the definitions of types A and B2 radical hysterectomy, which were the main innovations of the 2017 updated version of the 2008 Querleu-Morrow classification. Questions with the highest consensus rates concerned the definitions of types B1 and C, which are the most frequently performed radical hysterectomies. The 2017 version of the Querleu-Morrow classification proved to be a robust tool for defining and describing the extent of radical hysterectomies with a high level of consensus among international experts in gynecologic oncology. Knowledge and implementation of the exact definitions of hysterectomy radicality are imperative in clinical practice and clinical research. [ABSTRACT FROM AUTHOR]

Current guidelines for surveillance strategy in cervical cancer are rigid, recommending the same strategy for all survivors. The aim of this study was to develop a robust model allowing for individualised surveillance based on a patient's risk profile. Data of 4343 early-stage patients with cervical cancer treated between 2007 and 2016 were obtained from the international SCCAN (Surveillance in Cervical Cancer) consortium. The Cox proportional hazards model predicting disease-free survival (DFS) was developed and internally validated. The risk score, derived from regression coefficients of the model, stratified the cohort into significantly distinctive risk groups. On its basis, the annual recurrence risk model (ARRM) was calculated. Five variables were included in the prognostic model: maximal pathologic tumour diameter; tumour histotype; grade; number of positive pelvic lymph nodes; and lymphovascular space invasion. Five risk groups significantly differing in prognosis were identified with a five-year DFS of 97.5%, 94.7%, 85.2% and 63.3% in increasing risk groups, whereas a two-year DFS in the highest risk group equalled 15.4%. Based on the ARRM, the annual recurrence risk in the lowest risk group was below 1% since the beginning of follow-up and declined below 1% at years three, four and >5 in the medium-risk groups. In the whole cohort, 26% of recurrences appeared at the first year of the follow-up, 48% by year two and 78% by year five. The ARRM represents a potent tool for tailoring the surveillance strategy in early-stage patients with cervical cancer based on the patient's risk status and respective annual recurrence risk. It can easily be used in routine clinical settings internationally. • The recurrence risk model in cervical cancer was composed of five prognostic factors. • The developed annual recurrence risk model (ARRM) stratifies the cohort into five significantly distinctive risk groups. • The ARRM represents a powerful tool for tailoring of appropriate surveillance strategy. • The ARRM can easily be used in routine clinical settings internationally. [ABSTRACT FROM AUTHOR]

Cervical cancer is increasingly diagnosed in women who have not yet completed their reproductive plans. For women with early-stage disease (FIGO stage IA1-IB1), fertility-sparing procedures, such as conization, trachelectomy or radical trachelectomy, represent the treatments of choice. However, women who undergo repeated conization or trachelectomy represent a challenge for obstetricians because they are at increased risk of infertility, mid-trimester miscarriage, preterm premature rupture of membranes and preterm delivery. So far, the evidence-based guidance on the management of these pregnancies is limited. This article reviews the literature discussing pregnancy management in women after fertility-sparing surgery for early cervical cancer. Although the evidence is limited, certain measures are desirable, including screening and treatment of asymptomatic bacteriuria, screening for cervical incompetence and progressive cervical shortening by transvaginal ultrasonography, and fetal fibronectin testing. Vaginal progesterone supplementation should be primary prevention for all women after trachelectomy. Women with a history of preterm delivery or late miscarriage may benefit from cervical cerclage. Elective delivery by cesarean section in the early-term period is desirable. [ABSTRACT FROM AUTHOR]

Background: Radical trachelectomy is considered a viable option for fertility preservation in patients with low-risk, early-stage cervical cancer. Standard approaches include laparotomy or minimally invasive surgery when performing radical trachelectomy. Primary Objective: To compare disease-free survival between patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive (laparoscopic or robotic) radical trachelectomy. Study Hypothesis: We hypothesize that minimally invasive radical trachelectomy has similar oncologic outcomes to those of the open approach. Study Design: This is a collaborative, multi-institutional, international, retrospective study. Patients who underwent a radical trachelectomy and lymphadenectomy between January 1, 2005 and December 31, 2017 will be included. Institutional review board approval will be required. Each institution will be provided access to a study-specific REDCap (Research Electronic Data Capture) database maintained by MD Anderson Cancer Center and will be responsible for entering patient data. Inclusion Criteria: Patients with squamous, adenocarcinoma, or adenosquamous cervical cancer FIGO (2009) stages IA2 and IB1 (≤2 cm) will be included. Surgery performed by the open approach or minimally invasive approach (laparoscopy or robotics). Tumor size ≤2 cm, by physical examination, ultrasound, MRI, CT, or positron emission tomography (at least one should confirm a tumor size ≤2 cm). Centers must contribute at least 15 cases of radical trachelectomy (open, minimally invasive, or both). Exclusion Criteria: Prior neoadjuvant chemotherapy or radiotherapy to the pelvis for cervical cancer at any time, prior lymphadenectomy, or pelvic retroperitoneal surgery, pregnant patients, aborted trachelectomy (intra-operative conversion to radical hysterectomy), or vaginal approach. Primary Endpoint: The primary endpoint is disease-free survival measured as the time from surgery until recurrence or death due to disease. To evaluate the primary objective, we will compare disease-free survival among patients with FIGO (2009) stage IA2 or IB1 (≤2cm) cervical cancer who underwent open versus minimally invasive radical trachelectomy. Sample Size: An estimated 535 patients will be included; 256 open and 279 minimally invasive radical trachelectomy. Previous studies have shown that recurrence rates in the open group range from 3.8% to 7.6%. Assuming that the 4.5-year disease-free survival rate for patients who underwent open surgery is 95.0%, we have 80% power to detect a 0.44 HR using α level 0.10. This corresponds to an 89.0% disease-free survival rate at 4.5 years in the minimally invasive group. [ABSTRACT FROM AUTHOR]

Abstract Sentinel lymph node (SLN) biopsy has been increasingly used in the management of early-stages cervical cancer instead of systematic pelvic lymph node dissection (PLND). The aim of this article is to give a critical overview of key aspects related to this concept, such as a necessity for reliable detection of micrometastases (MIC) in SLN and the requirements for SLN pathologic ultrastaging, low accuracy of intraoperative detection of SLN involvement, and still a limited evidence of oncological safety of the replacement of PLND by SLN biopsy only in ≥IB1 tumours due to unknown risk of MIC in non-SLN pelvic lymph nodes in patients with negative SLN, and absence of any prospective evidence. Highlights • Detection of micrometastases increases sensitivity of SLN, so SLN ultrastaging should be performed if PLND is avoided. • Intraoperative SLN evaluation fails to detect 30–50% of metastases. • Micrometastases in SLN is associated with decreased survival equivalent to macrometastases. • The risk of micrometastases in pelvic LN in cases with negative SLN is not known. • There is no prospective evidence on safety of SLN only concept in cervical cancer. [ABSTRACT FROM AUTHOR]

Objective: Sentinel lymph node (SLN) biopsy has been increasingly used in the management of early-stage cervical cancer. It appears in guidelines as an alternative option to systematic pelvic lymphadenectomy. The evidence about safety is, however, based mostly on retrospective studies, in which SLN was combined with systematic lymphadenectomy. Materials and methods: SENTIX is a prospective multicenter trial aiming to prove that less-radical surgery with SLN is non-inferior to treatment with systematic pelvic lymphadenectomy. The primary end point is recurrence rate; the secondary end point is the prevalence of lower-leg lymphedema and symptomatic pelvic lymphocele. The reference recurrence rate was set up conservatively at 7% at 24 months after treatment. With a sample size of 300 patients treated per protocol, the trial is powered to detect a non-inferiority margin of 5% (90% power, p = 0.05) for recurrence rate, 30% reduction in the prevalence of symptomatic lymphocele or lower-leg lymphedema, with reference rates of 30% and 6% at 12 months (p = 0.025, Bonferroni correction). The patients eligible for SENTIX have stage IA1/LVSI+, IA2, IB1 (<2 cm for fertility sparing), with negative LN on pre-operative imaging. Intra-operatively, patients are excluded when there is a failure to detect SLN on both sides of the pelvis in cases of more advanced cancer (stage >IB1), or a positive intra-operative SLN assessment. The quality of SLN pathology evaluation will be assessed by central review. Three interim safety analyses are pre-planned when 30, 60, 150 patients complete 12 months' follow-up. Conclusions: The first patient was enrolled into the study in June 2016 and, by June 2018, 340 patients had been enrolled. The first analysis of secondary outcomes should be available in 2019 and the oncological outcome of 300 patients at the end of 2021. The trial is registered as a CEEGOG trial (CEEGOG CX-01), ENGOT trial (ENGOT-Cx 2), and at the ClinicalTrials.gov database (NCT02494063). [ABSTRACT FROM AUTHOR]

Objective: The aim of this survey was to acquire an overview of the current management of cervical cancer with an emphasis on the early disease stages. Materials and Methods: A hyperlink to the survey was sent to the European Society of Gynaecological Oncology Office database. The survey contained 6 groups of questions regarding the characteristics of respondents, pretreatment workup, management of the early stages of cervical cancer, adjuvant treatment, fertility-sparing treatment, and surveillance. Results: In total, 566 responses were collected. The most frequent imaging method used in the workup was magnetic resonance imaging (74%), followed by computed tomography (54%) and positron emission tomography/computed tomography (25%). Conization or simple hysterectomy was a preferred procedure in stage T1a1 lymphovascular space invasion (LVSI)–positive for 79% of respondents, in stage T1a2 LVSI-negative for 58%, and in stage T1a2 LVSI-positive for 28%. Sentinel lymph node biopsy alone was reported in stage T1a1 by 17% and in stage T1b1 less than 2 cm by 9%, whereas systematic lymphadenectomy by 29% and 90% of respondents. Macrometastases, micrometastases, and isolated tumor cells in lymph nodes were considered indications for adjuvant treatment by 96%, 93%, and 68% of respondents, respectively. Neoadjuvant chemotherapy was reported by 28% and 19% of respondents in fertility-sparing and nonsparing management in stage T1b1. Over 60% of respondents recommend primary surgery for their patients with T1b2 N0 disease and 81% of them use a combination of adverse prognostic factors as indication for adjuvant radiotherapy in pN0 disease. Conclusions: The results of this survey indicate considerable differences in the workup and treatment of cervical cancer in current clinical practice. [ABSTRACT FROM AUTHOR]

Objective: The aim of our study was to compare the sensitivity of various methods and their combinations in the follow-up of patients with cervical cancer after fertility-sparing surgery (FSS). Methods: Included were women with cervical cancer in stages IA2 to IB2 who underwent FSS, which includes pelvic lymphadenectomy, sentinel lymph node biopsy, abdominal radical trachelectomy, vaginal trachelectomy, or needle conization. Follow-up visits were scheduled at 3-month intervals and included symptom-oriented discussion, gynecological and physical examination, colposcopy, Papanicolaou test, human papillomavirus (HPV) DNA test, and ultrasound examination. All cases with a recurrent disease were thoroughly analyzed, and the results of individual examinations were compared. Results: In total, 43 women (IA2, 8; IB1, 33; IB2, 2) were enrolled. The mean patient age was 31 years; most patients were nulliparous (68.4%, 26/38) with squamous cell cancers (26/38). Abdominal radical trachelectomy was performed in 10 women, simple vaginal trachelectomy was performed in 11 women, and conization was performed in 22 women, according to the tumor characteristics and topography. The median duration of the follow-up reached 37 months. Invasive cancer and high- and low-grade squamous intraepithelial lesions were detected in 8, 1, and 1 patients, respectively. All except 1 event were central, detected within the first year after FSS. Only 2 cases were symptomatic. Colposcopy detected 7 of 10 recurrences; 5 of them were HPV positive, and, in 2 cases, a Papanicolaou test revealed abnormalities. Papanicolaou tests were false positive in 27.7%, especially after trachelectomies. Conclusions: Most patients in whom cancer recurred after FSS reveal central or pelvic lesions, which can be successfully treated with salvage surgery or radiotherapy. The early detection of recurrence is an essential condition for a favorable oncological outcome. Colposcopy alone and in combination with HPV positivity showed the highest sensitivity for the detection of recurrent diseases, whereas other methods had limited reliability. [ABSTRACT FROM AUTHOR]

The recently published ABRAX (ABandoning RAd hyst in cerviX cancer) study has not shown any survival benefit resulting from a completion of radical hysterectomy in patients with common cervical cancer types, in whom positive pelvic lymph nodes were diagnosed intraoperatively. Completion of radical hysterectomy does not improve survival of patients with cervical cancer and intraoperatively detected lymph node involvement: ABRAX international retrospective cohort study. Cibula D. Int J Gynecol Cancer 2021;31:502-503. doi:10.1136/ijgc-2021-002510 502 Rationale for the avoidance of parametrectomy and systematic lymphadenectomy in patients with early stages of neuroendocrine cervical cancer David Cibula Department of Obstetrics and Gynecology, General University Hospital in Prague, First Faculty of Medicine, Charles University, Prague, Czech Republic Correspondence to Dr David Cibula, Department of Obstetrics and Gynecology, University of Prague, Prague 118 00, Czech Republic; dc@ da vidcibula. cz Received 8 February 2021 Accepted 9 February 2021 Published Online First 18 March 2021 To cite: Cibula D. Int J Gynecol Cancer 2021;31:502- 503. [Extracted from the article]

The accurate harvesting of a sentinel node in gynaecological cancer (i.e. vaginal, vulvar, cervical, endometrial or ovarian cancer) includes a sequence of procedures with components from different medical specialities (nuclear medicine, radiology, surgical oncology and pathology). These guidelines are divided into sectione entitled: Purpose, Background information and definitions, Clinical indications and contraindications for SLN detection, Procedures (in the nuclear medicine department, in the surgical suite, and for radiation dosimetry), and Issues requiring further clarification. The guidelines were prepared for nuclear medicine physicians. The intention is to offer assistance in optimizing the diagnostic information that can currently be obtained from sentinel lymph node procedures. If specific recommendations given cannot be based on evidence from original scientific studies, referral is made to 'general consensus' and similar expressions. The recommendations are designed to assist in the practice of referral to, and the performance, interpretation and reporting of all steps of the sentinel node procedure in the hope of setting state-of-the-art standards for high-quality evaluation of possible metastatic spread to the lymphatic system in gynaecological cancer. The final result has been discussed by a group of distinguished experts from the EANM Oncology Committee and the European Society of Gynaecological Oncology (ESGO). The document has been endorsed by the SNMMI Board. [ABSTRACT FROM AUTHOR]

Background: Minimally invasive radical trachelectomy has emerged as an alternative to open radical hysterectomy for patients with early-stage cervical cancer desiring future fertility. Recent data suggest worse oncologic outcomes after minimally invasive radical hysterectomy than after open radical hysterectomy in stage I cervical cancer.Objective: We aimed to compare 4.5-year disease-free survival after open vs minimally invasive radical trachelectomy.Study Design: This was a collaborative, international retrospective study (International Radical Trachelectomy Assessment Study) of patients treated during 2005-2017 at 18 centers in 12 countries. Eligible patients had squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma; had a preoperative tumor size of ≤2 cm; and underwent open or minimally invasive (robotic or laparoscopic) radical trachelectomy with nodal assessment (pelvic lymphadenectomy and/or sentinel lymph node biopsy). The exclusion criteria included neoadjuvant chemotherapy or preoperative pelvic radiotherapy, previous lymphadenectomy or pelvic retroperitoneal surgery, pregnancy, stage IA1 disease with lymphovascular space invasion, aborted trachelectomy (conversion to radical hysterectomy), or vaginal approach. Surgical approach, indication, and adjuvant therapy regimen were at the discretion of the treating institution. A total of 715 patients were entered into the study database. However, 69 patients were excluded, leaving 646 in the analysis. Endpoints were the 4.5-year disease-free survival rate (primary), 4.5-year overall survival rate (secondary), and recurrence rate (secondary). Kaplan-Meier methods were used to estimate disease-free survival and overall survival. A post hoc weighted analysis was performed, comparing the recurrence rates between surgical approaches, with open surgery being considered as standard and minimally invasive surgery as experimental.Results: Of 646 patients, 358 underwent open surgery, and 288 underwent minimally invasive surgery. The median (range) patient age was 32 (20-42) years for open surgery vs 31 (18-45) years for minimally invasive surgery (P=.11). Median (range) pathologic tumor size was 15 (0-31) mm for open surgery and 12 (0.8-40) mm for minimally invasive surgery (P=.33). The rates of pelvic nodal involvement were 5.3% (19 of 358 patients) for open surgery and 4.9% (14 of 288 patients) for minimally invasive surgery (P=.81). Median (range) follow-up time was 5.5 (0.20-16.70) years for open surgery and 3.1 years (0.02-11.10) years for minimally invasive surgery (P<.001). At 4.5 years, 17 of 358 patients (4.7%) with open surgery and 18 of 288 patients (6.2%) with minimally invasive surgery had recurrence (P=.40). The 4.5-year disease-free survival rates were 94.3% (95% confidence interval, 91.6-97.0) for open surgery and 91.5% (95% confidence interval, 87.6-95.6) for minimally invasive surgery (log-rank P=.37). Post hoc propensity score analysis of recurrence risk showed no difference between surgical approaches (P=.42). At 4.5 years, there were 6 disease-related deaths (open surgery, 3; minimally invasive surgery, 3) (log-rank P=.49). The 4.5-year overall survival rates were 99.2% (95% confidence interval, 97.6-99.7) for open surgery and 99.0% (95% confidence interval, 79.0-99.8) for minimally invasive surgery.Conclusion: The 4.5-year disease-free survival rates did not differ between open radical trachelectomy and minimally invasive radical trachelectomy. However, recurrence rates in each group were low. Ongoing prospective studies of conservative management of early-stage cervical cancer may help guide future management. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the sensitivity of sentinel node (SN) ultrastaging and to define parameters that may reduce the overall false-negative rate in women with early-stage cervical cancer. Methods: We analyzed data from a large retrospective multicenter cohort group with FIGO stages IA–IIB cervical cancer in whom at least one SN was identified and systematic pelvic lymphadenectomy was uniformly performed. All who were SN negative by initial evaluation were subjected to ultrastaging. Results: In all, 645 patients were evaluable. SN were detected bilaterally in 72% of cases and unilaterally in 28%. Patients with optimal bilateral SN detection were significantly more likely to have any metastasis detected (33.3% vs. 19.2%; P <0.001) as well as micrometastasis detected in their SN (39.6% vs. 11.4%). SN ultrastaging resulted in a low overall false-negative rate of 2.8% (whole group) and an even lower false-negative rate of 1.3% for patients with optimal bilateral mapping. Patients with false-negative SN after ultrastaging had a higher prevalence of LVSI and more frequent unilateral SN detection. Sensitivity of SN ultrastaging was 91% (95% CI: 86%–95%) for the whole group and 97% (95% CI: 91%–99%) in the subgroup with bilateral SN detection. Conclusion: These data confirm previous observations that optimal bilateral SN detection substantially decreases the false negative rate of SN ultrastaging and increases detection of micrometastasis. In patients with bilateral SN detection, the sensitivity of SN ultrastaging is not reduced in more advanced stages of the disease. SN mapping and ultrastaging should become standard practice in the surgical management of early-stage cervical cancer. [Copyright &y& Elsevier]

Abdominal radical trachelectomy (ART) is a type C resection (uterine vessels ligated at origin from the hypogastric vessels). Questions arise as to whether fertility is maintained after ART, particularly when uterine vessels are sacrificed. We report an international series on ART to describe fertility and oncologic outcomes.Databases at 3 institutions were queried to identify patients planned for ART from 1999 to 2011. Clinical and demographic data were gathered.One hundred one patients underwent ART. Mean age was 31 years (range, 19-43 years). Histologic classifications were adenocarcinoma (n = 54), squamous cell carcinoma (n = 40), adenosquamous carcinoma (n = 6), and clear cell carcinoma (n = 1). Twenty patients (20%) required conversion to hysterectomy (10 margins and 10 nodes). Eight patients underwent completion hysterectomy owing to the following: positive margins on final pathology (n = 3), patient’s choice (n = 4), or recurrence (n = 1). Postoperatively, 20 patients (20%) received adjuvant chemotherapy and/or radiation (4 final pathology margins and 16 nodes). Four patients (4%) had recurrence and lived 22 to 35 months after diagnosis. Of the 70 women who had neither hysterectomy nor adjuvant therapy, 38 (54%) attempted pregnancy and 28 (74%) achieved pregnancy. Thirty-one pregnancies resulted in 16 (52%) third trimester deliveries. Six patients are currently pregnant with outcomes pending.These data demonstrate that ART preserves fertility and maintains excellent oncologic outcomes. Most women (74%) attempting pregnancy after ART are able to achieve pregnancy and deliver in the third trimester (52%). Preservation of the uterine vasculature is not necessary for fertility; obstetrical outcomes are similar to those of the historical vaginal radical trachelectomy cohorts. [ABSTRACT FROM AUTHOR]

It was the aim of our study to analyze oncological outcome and prognostic parameters in patients with early stages cervical cancer after tailored and well-standardized surgical treatment with an adequate follow-up.Oncological outcome and prognostic parameters were evaluated in a group of 192 patients with cervical cancer stages IA2 to 2B who had undergone radical hysterectomy (n = 171), radical parametrectomy (n = 12), or radical trachelectomy (n = 9). Procedures were classified as type B (n = 72), type C1 nerve sparing (n = 103), or type C2 (n = 17).Event-free and overall 5-year survivals probabilities reached 92.7% (confidence interval, 89.5%-95.9 %) and 94.1% (confidence interval, 90.9%-97.3 %). There was only 1 isolated pelvic recurrence found of the total of 10 recurrences. Adjuvant radiotherapy was given to only 22% of patients. The most significant independent prognostic parameters in stage IB tumors were lymph node status, histological type, and tumor volume, whereas in stage II, the parameters included histological type and tumor volume, the latter being inversely related to the prognosis.We have shown an excellent prognosis, especially local control, after tailored surgical treatment of stages IA2 to IIB of cervical cancer, with low prevalence of adjuvant treatment. Different prognostic parameters were observed for stages IB1/IB2 and IIA/B. [ABSTRACT FROM AUTHOR]

The impairment of spontaneous voiding is the most prominent type of morbidity in the early postoperative period after radical hysterectomy. The aim of our work was to evaluate the parameters affecting the recovery of spontaneous voiding.Enrolled were women in whom radical procedure for early-stage cervical cancer was performed in the period from 2006 to 2008. Satisfactory spontaneous voiding was characterized by the reduction of postvoiding urine residuum to 50 mL or less in the course of a whole day.Data from 85 patients were evaluated retrospectively (radical hysterectomy 67, radical parametrectomy 6, and radical trachelectomy 12), of which 35 underwent nerve-sparing modification, 19 underwent type C radicality of procedure, and 31 underwent type D radicality of procedure. Radicality of parametrectomy was the most significant parameter influencing the interval to spontaneous voiding recovery (P < 0.05); significant differences were observed between nerve-sparing and type D procedures. Multivariate analysis revealed 3 significant parameters: procedure radicality (P < 0.001), type of procedure (radical hysterectomy vs radical trachelectomy; P < 0.05), and a negative correlation with body mass index (P < 0.05). Long-term spontaneous voiding impairment lasting more than 6 weeks was observed in 7 patients, of whom 5 had undergone type D procedure.The radicality of parametrial resection is the most prominent factor determining the interval to spontaneous voiding, with significantly poorer outcomes after type D procedure. Interestingly, another significant parameter in our study was the type of parametrectomy, with better outcomes achieved after radical trachelectomy. Delayed voiding recovery was observed in patients with lower body mass index. [ABSTRACT FROM AUTHOR]

This work intends to present a systematic overview of data that have been published so far with regard to methods used for tissue sampling and DNA testing and with regard to the prevalence of human papillomavirus (HPV) DNA in pelvic lymph nodes (LNs) and its prognostic significance.The HPV DNA status of LN in women with cervical cancer is being explored as a potential marker of "occult" metastases. Although the presence of HPV DNA in LN usually correlates with its metastatic involvement, there is always a subgroup of HPV-positive but histologically negative LNs.The significance of HPV in negative LNs remains uncertain, although several studies have concluded that HPV is a risk factor of recurrence.A small group size and a short follow-up are the main limitations for drawing any conclusion concerning prognostic significance of the presence of HPV DNA in LNs. [ABSTRACT FROM AUTHOR]

Abdominal radical trachelectomy (ART) is one of the fertility-sparing procedures in women with early-stage cervical cancer. In comparison with vaginal radical trachelectomy, the published results of ART are so far limited.Enrolled were women referred for ART either by laparoscopy or laparotomy. The main inclusion criterion was stage IA2 or IB1 with a cranial extent that allows for preservation of at least 1 cm of the endocervical canal.A total of 24 women were referred for the procedure, but fertility could not be preserved in 7 (29%) of them. Four women underwent immediate completion of radical hysterectomy because of a positive cranial surgical margin (n = 2) or sentinel node macrometastasis (n = 2) on frozen section. We found no correlation between tumor volume and inability to preserve fertility. A positive sentinel node was identified in 4 patients (17%); there were no false-negative results. Of the 9 women (53%) who have tried to conceive so far, 6 (67%) have conceived and 5 given birth, 2 of which were premature deliveries.Fertility cannot be preserved because of positive cranial margins or involved lymph nodes in almost one third of patients originally referred for radical trachelectomy. The main criterion for the selection of suitable patients should be the cranial extent of the tumor. Abdominal radical trachelectomy allows for achievement of satisfactory obstetrical outcomes. [ABSTRACT FROM AUTHOR]

Metastatic involvement of pelvic lymph nodes is the most important prognostic parameter in early-stage cervical cancer. Still, approximately 15% of patients with negative pelvic nodes experience recurrence, most of them in the pelvis. The presence of human papillomavirus (HPV) DNA in histologically negative pelvic nodes is considered a subclinical metastatic spread.Patients with early-stage cervical cancer referred for surgical treatment were enrolled in the study. Cytobrush technique was used for sample collection from the fresh tissue to avoid any loss of material for histology.Altogether, 49 patients were enrolled in the study. High-risk (HR) HPV DNA was identified in the tumor in 91.8% patients and in the sentinel node or other pelvic nodes in 49.9% patients. Among the 10 HR HPV genotypes detected, HPV 16 was the most frequently represented in both the tumor and the lymph nodes (66.7% and 71.4%, respectively). All metastatic lymph nodes were HR HPV positive.The presence of HR HPV DNA in a sentinel node had a 100% positive predictive value for metastatic involvement of pelvic lymph nodes in our study. This could be considered a sign of an early subclinical metastatic spread; however, the prognostic value has to be evaluated through a longer follow-up. [ABSTRACT FROM AUTHOR]

Background: Metastatic affection of pelvic lymph nodes is the most important prognostic parameter in early stages cervical cancer. Still, serious number of patients with negative pelvic nodes experience recurrence, majority of them are local in pelvis. High frequency positivity of DNA of the most common high risk (HR) genotypes HPV-16 and 18 was shown in histopathology-negative pelvic nodes, and is considered as subclinical metastatic spread. Limited data are available concerning presence of different HR genotypes and correlation between HR HPV DNA in sentinel lymph nodes (SLN), other pelvic nodes and the primary tumor. Prognostic significance of such findings is still uncertain. Objectives: Main objective of the study was to evaluate the presence of HR HPV DNA including 13 genotypes in pelvic SLN, other pelvic non-SLN nodes and in the tumor. Material and Methods: Enrolled were patients with early-stage cervical cancer referred for surgical treatment including systematic pelvic lymphadenectumy. During the surgery, samples for HR HPV assesment were taken from tumor tissue, sentinel node and the pelvic nodes. All samples were evaluated for the presence of HR HPV and genotyped for the main 13 genotypes. Results: The study included 49 patients (FIGO IA2 - 2B) who underwent radical hysterectomy with systematic pelvic lymphadenectomy and sentinel lymph node biopsy. 91.8% patients had HR HPV DNA in their primary tumors, 49,9% patients in SLN and other pelvic nodes. In 1 case we found HR HPV DNA in pelvic nodes without positivity of SLN. We found 9 different genotypes of HR HPV in the examinated tissue. There were 6 cases with histopatologically confirmed nodal metastases, all of them were also HR HPV DNA positive with agreement between genotype in the primary tumor, SLN and other pelvic nodes. Conclusions: Our results show that the presence of HR HPV DNA in pelvic lymph nodes is an early sign of disease progression to the pelvis. Concordance between HPV genotype in the primary tumor and the involved pelvic lymph nodes is necessary. [ABSTRACT FROM AUTHOR]

In order to define the clinical significance of low-volume metastasis, a comprehensive meta-analysis of published data and individual data obtained from articles mentioning micrometastases (MIC) and isolated tumor cells (ITC) in cervical cancer was performed, with a follow up of at least 3 years. We performed a systematic literature review and meta-analysis, following Cochrane's review methods guide and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcome was the disease-free survival (DFS), and the secondary outcome was the overall survival (OS). The hazard ratio (HR) was taken as the measure of the association between the low-volume metastases (MIC+ITC and MIC alone) and DFS or OS; it quantified the hazard of an event in the MIC (+/− ITC) group compared to the hazard in node-negative (N0) patients. A random-effect meta-analysis model using the inverse variance method was selected for pooling. Forest plots were used to display the HRs and risk differences within individual trials and overall. Eleven articles were finally retained for the meta-analysis. In the analysis of DFS in patients with low-volume metastasis (MIC + ITC), the HR was increased to 2.60 (1.55–4.34) in the case of low-volume metastasis vs. N0. The presence of MICs had a negative prognostic impact, with an HR of 4.10 (2.71–6.20) compared to N0. Moreover, this impact was worse than that of MIC pooled with ITCs. Concerning OS, the meta-analysis shows an HR of 5.65 (2.81–11.39) in the case of low-volume metastases vs. N0. The presence of MICs alone had a negative effect, with an HR of 6.94 (2.56–18.81). In conclusion, the presence of MIC seems to be associated with a negative impact on both the DFS and OS and should be treated as MAC. • We performed a meta-analysis of published and individual data to define the significance of low-volume metastasis. • The presence of micrometastases seems to be associated with a negative impact on the disease-free survival. • Patients with isolated tumor cells should be considered like negative lymph node patients. [ABSTRACT FROM AUTHOR]

Highlights: [•] Cervarix® demonstrated, in clinical trials, an overall 93.2% efficacy against CIN3+. [•] This efficacy translates into a large number of lives saved in all countries; an additional 18–34% more lives saved than expected based on protection against HPV-16/18 only. [•] Public health benefit also includes reduction in costs, morbidity and suffering. [ABSTRACT FROM AUTHOR]

Abstract: Background: More than 90% of cases of anal cancers are caused by high-risk human papillomavirus (HR HPV) infection and a history of cervical intraepithelial neoplasia (CIN) is established as possible risk factor. Objectives: To demonstrate relationship between anal and cervical HPV infection in women with different grades of CIN and microinvasive cervical cancer. Study design: 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 Cobas and Lynear array HPV test. Results: Cervical, anal, and concurrent cervical and 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 of the cervix and anus occurred 5.3-fold more often in the study group than in the control group. Any contact with the anus was the only significant risk factor for development of concurrent HPV infection. Conclusions: Concurrent anal and cervical HR HPV infection was found in nearly half of women with CIN 2+. The dominant genotype found in both anatomical locations was HPV 16. Any frequency and any type of contact with the anus were shown as the most important risk factor for concurrent HPV infection. [Copyright &y& Elsevier]

Background: Few effective second-line treatments exist for women with recurrent or metastatic cervical cancer. Accordingly, we aimed to evaluate the efficacy and safety of tisotumab vedotin, a tissue factor-directed antibody-drug conjugate, in this patient population.Methods: This multicentre, open-label, single-arm, phase 2 study was done across 35 academic centres, hospitals, and community practices in Europe and the USA. The study included patients aged 18 years or older who had recurrent or metastatic squamous cell, adenocarcinoma, or adenosquamous cervical cancer; disease progression on or after doublet chemotherapy with bevacizumab (if eligible by local standards); who had received two or fewer previous systemic regimens for recurrent or metastatic disease; had measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1); and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received 2·0 mg/kg (up to a maximum of 200 mg) tisotumab vedotin intravenously once every 3 weeks until disease progression (determined by the independent review committee) or unacceptable toxicity. The primary endpoint was confirmed objective response rate based on RECIST (version 1.1), as assessed by the independent review committee. Activity and safety analyses were done in patients who received at least one dose of the drug. This study is ongoing with recruitment completed and is registered with ClinicalTrials.gov, NCT03438396.Findings: 102 patients were enrolled between June 12, 2018, and April 11, 2019; 101 patients received at least one dose of tisotumab vedotin. Median follow-up at the time of analysis was 10·0 months (IQR 6·1-13·0). The confirmed objective response rate was 24% (95% CI 16-33), with seven (7%) complete responses and 17 (17%) partial responses. The most common treatment-related adverse events included alopecia (38 [38%] of 101 patients), epistaxis (30 [30%]), nausea (27 [27%]), conjunctivitis (26 [26%]), fatigue (26 [26%]), and dry eye (23 [23%]). Grade 3 or worse treatment-related adverse events were reported in 28 (28%) patients and included neutropenia (three [3%] patients), fatigue (two [2%]), ulcerative keratitis (two [2%]), and peripheral neuropathies (two [2%] each with sensory, motor, sensorimotor, and neuropathy peripheral). Serious treatment-related adverse events occurred in 13 (13%) patients, the most common of which included peripheral sensorimotor neuropathy (two [2%] patients) and pyrexia (two [2%]). One death due to septic shock was considered by the investigator to be related to therapy. Three deaths unrelated to treatment were reported, including one case of ileus and two unknown causes.Interpretation: Tisotumab vedotin showed clinically meaningful and durable antitumour activity with a manageable and tolerable safety profile in women with previously treated recurrent or metastatic cervical cancer. Given the poor prognosis for this patient population and the low activity of current therapies in this setting, tisotumab vedotin, if approved, would represent a new treatment for women with recurrent or metastatic cervical cancer.Funding: Genmab, Seagen, Gynaecologic Oncology Group, and European Network of Gynaecological Oncological Trial Groups. [ABSTRACT FROM AUTHOR]

Objective The aim of our study was to describe oncological and obstetrical outcomes in patients who underwent less radical fertility-sparing surgical (FSS) procedures with omitted parametrectomy for cervical cancer. Methods Included were women with cervical cancer stages IA2–IB2 who were under the age of 40 and desired future pregnancy. Patients underwent pelvic lymphadenectomy and sentinel lymph node biopsy. Node-negative cases underwent subsequent cervical surgery and were further analyzed. Neoadjuvant chemotherapy (NAC) was administered in patients with tumors > 2 cm and/or involving > 2/3 of cervical stroma. Simple vaginal trachelectomy or needle conization were performed according to tumor extent and topography. The follow-up period started once free surgical margins were reached. Results Out of 44 women enrolled, 32 women (IA2 = 7, IB1 = 23, IB2 = 2) successfully completed FSS. NAC was administered in 9 (28.1%) cases. A simple trachelectomy was performed in 11 patients and needle conization in 21 patients. During the follow-up, 6 out of 32 women became pregnant. Of these, 1 miscarried and 5 successfully delivered. Disease recurred in 6 patients; 5 recurrences were central and 1 recurrence presented as an ovarian mass. Invasive cervical carcinoma, high-grade squamous intraepithelial (HSIL), and low-grade squamous intraepithelial (LSIL) lesions were detected in 4, 1 and 1 patients, respectively. Three of them received NAC. All events were detected within 16 months after surgery. Conclusions Nearly 27% of patients cannot complete FSS due to node positivity, progression during NAC, or involved margins. The total recurrence rate reached 18.8%, with the majority of invasive recurrences detected in patients after NAC followed by FSS. These patients represent cases at a higher risk of recurrence even if adequate free margins are reached by surgery. Nearly half of the cohort did not consider pregnancy in the near future because of personal reasons. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To compare the diagnostic accuracy of ultrasound (US) and magnetic resonance imaging (MRI) in the preoperative assessment of early-stage cervical cancer using pathologic findings as the reference standard. Patients and methods: Prospective multi-center trial enrolling 209 consecutive women with early-stage cervical cancer (FIGO IA2–IIA) scheduled for surgery. The following parameters were assessed on US and MRI and compared to pathology: remaining tumor, size, tumor stromal invasion<2/3 (superficial) or ≥2/3 (deep), and parametrial invasion. Results: Complete data were available for 182 patients. The agreement between US and pathology was excellent for detecting tumors, correctly classifying bulky tumors (>4cm), and detecting deep stromal invasion (kappa values 0.84, 0.82, and 0.81 respectively); and good for classifying small tumors (<2cm) and detecting parametrial invasion (kappa values 0.78 and 0.75, respectively). The agreement between MRI and histology was good for classifying tumors as <2cm, or >4cm, and detecting deep stromal invasion (kappa values 0.71, 0.76, and 0.77, respectively). It was moderately accurate in tumor detection, and in assessing parametrial invasion (kappa values 0.52 and 0.45, respectively). The agreement between histology and US was significantly better in assessing residual tumor (p <0.001) and parametrial invasion (p <0.001) than the results obtained by MRI. Imaging methods were not significantly influenced by previous cone biopsy. Conclusion: US and MRI are highly accurate for the preoperative assessment of women with early-stage cervical cancer, although US may be more accurate in detecting residual tumors and assessing parametrial invasion. [Copyright &y& Elsevier]

Abstract: Background: Paraaortic lymph nodes represent the second level in the lymphatic spread of cervical cancer. Recent studies have confirmed the association of HPV DNA in pelvic lymph nodes in early-stage disease with metastatic involvement and a less favourable prognosis. Objective: The aim of our study was to detect 13 high-risk genotypes of HPV in paraaortic nodes harvested from patients with FIGO IB2–IIIB tumours and correlate findings with histopathology. Study design: The study involved patients with advanced cervical cancer who had undergone low paraaortic lymphadenectomy. The cytobrush technique was used for perioperative sample collection from the tumour and fresh lymphatic tissue. Patients with non-HPV related cancers were used as a control group. Results: The study involved 24 cervical cancer patients. High-risk HPV DNA was found in the primary tumour of all cases and in PALN in 16 (67%) cases. The most frequent genotype was HPV 16, both in the tumour and in the paraaortic lymph nodes (83% and 54%, respectively). Metastatic involvement of paraaortic lymph nodes was identified in 8 cases (33%), which all were also HPV DNA positive. No HPV DNA was detected in PALN in any of 22 control group cases. Conclusions: Using the cytobrush technique, the presence of at least one HR HPV genotype in the primary tumour was identified in all the patients. The metastatically involved paraaortic lymph nodes always contained the DNA of at least one HPV genotype present in the primary tumour. Determination of clinical significance of HR HPV DNA presence in histologically negative lymph nodes requires further follow-up of the cohort. [ABSTRACT FROM AUTHOR]