Appropriateness of Mini-Invasive Approaches for Nausea and Vomiting Refractory to Medical Therapy in Palliative Care Setting: A Case Report.

Introduction: Nausea and vomiting are frequent multifactorial symptoms in oncological patients. These manifestations, mainly affecting the advanced disease stages, may lead to existential, psychological, and physical suffering, with a negative impact on the quality of life (QoL) of the individual and his family. The medical approach makes use of a wide range of drugs, with different antiemetic potency and various mechanisms of action, taking into account the etiology and the patient's response to the different therapeutic strategies. In recent years, in addition to pharmacological treatments, some endoscopic procedures have been integrated into clinical practice as promising palliative approaches. Case Presentation: Herein, we describe and discuss a case of a 64-year-old female affected by advanced stage pancreatic adenocarcinoma, in which different techniques - both medical and endoscopic - have been used to approach a refractory symptomatology with a negative impact on the patient's QoL. In the context of a multidisciplinary approach in primary palliative care, a tailored intervention encompassing invasive methods for palliative purposes, may be considered adequate and appropriate when the prognostic expectation and the physical functionality indices allow it. Conclusion: Minimally invasive palliative interventions should be offered to patients with advanced cancer when symptoms become refractory to standard medical therapies, as part of the holistic approach in modern treatments. Therefore, the integration of an early palliative approach into the patient's therapeutic path becomes essential for the management of all the individual's needs.

Transmission of ß-lactamases in the pork food chain: A public health concern.

Antimicrobial resistance (AMR) is a risk for public health that requires management in a One Health perspective, including humans, animals, and the environment. The food production chain has been identified as a possible route of transmission of AMR bacteria to humans. The most critical issue regards resistance to the Critically Important Antimicrobials (CIAs), such as ß-lactams antibiotics. Here, pigs were analysed along the entire food producing chain, including feces, carcasses and pork products (fresh meat, fermented and seasoned products) ensuring treaciability of all samples. Escherichia coli were isolated and their ability to produce ESBL and AmpC ß-lactamases was evaluated both phenotypically and genotypically. Strains with the same AMR profile from feces, carcasses, and meat products were selected for phylogenetic and comparative genomic analyses to evaluate the possible "farm-to-fork" transmission of ß-lactams resistant bacteria. Results showed that the percentage of ESBL strains in fecal E. coli was approximately 7% and increased slightly in the pork food chain: the 10% of ESBL E. coli isolated from carcasses and the 12.5% of isolates from fresh meat products. AmpC E. coli were found only in feces, carcasses, and fresh meat with a low prevalence. Results showed that of the 243 pigs followed along the entire food chain genetic similarities in E. coli isolated from farm-to-fork were found in only one pig (feces, carcasses and fresh meat). Frequent similarities were shown in resistant E. coli isolates from carcasses and fresh meat or fermented product (three pork food chain). Moreover, in one case, bacteria isolated from fresh meat and fermented product were genotypically similar. Concluding, direct transmission of ß-lactams resistance from farm-to-fork is possible but not frequent. Further studies are needed to improve risk communication to consumers and access to clear and reliable information and health concerns on food.

Clinical Utility and Application of Liquid Biopsy Genotyping in Lung Cancer: A Comprehensive Review.

Precision medicine has revolutionized the therapeutic management of cancer patients with a major impact on non-small cell lung cancer (NSCLC), particularly lung adenocarcinoma, where advances have been remarkable. Tissue biopsy, required for tumor molecular testing, has significant limitations due to the difficulty of the biopsy site or the inadequacy of the histological specimen. In this context, liquid biopsy, consisting of the analysis of tumor-released materials circulating in body fluids, such as blood, is increasingly emerging as a valuable and non-invasive biomarker for detecting circulating tumor DNA (ctDNA) carrying molecular tumor signatures. In advanced/metastatic NSCLC, liquid biopsy drives target therapy by monitoring response to treatment and identifying eventual genomic mechanisms of resistance. In addition, recent data have shown a significant ability to detect minimal residual disease in early-stage lung cancer, underlying the potential application of liquid biopsy in the adjuvant setting, in early detection of recurrence, and also in the screening field. In this article, we present a review of the currently available data about the utility and application of liquid biopsy in lung cancer, with a particular focus on the approach to different techniques of analysis for liquid biopsy and a comparison with tissue samples as well as the potential practical uses in early and advanced/metastatic NSCLC.

COVID-19 pandemic impact on cytopathology practice in the post-lockdown period: An international, multicenter study.

BACKGROUND: In a previous worldwide survey, the authors showed a drastic reduction in the number of cytological specimens processed during the coronavirus disease 2019 "lockdown" period along with an increase in malignancy rates. To assess the continued impact of the pandemic on cytological practices around the world, they undertook a second follow-up worldwide survey collecting data from the post-lockdown period (2020). METHODS: Participants were asked to provide data regarding their cytopathology activity during the first 12 weeks of their respective national post-lockdown period (2020), which ranged from April 4 to October 31. Differences between the post-lockdown period and the corresponding 2019 period were evaluated, and the authors specifically focused on rates of malignant diagnoses. RESULTS: A total of 29 respondents from 17 countries worldwide joined the survey. Overall, a lower number of cytological specimens (n = 236,352) were processed in comparison with the same period in 2019 (n = 321,466) for a relative reduction of 26.5%. The overall malignancy rate showed a statistically significant increase (12,442 [5.26%] vs 12,882 [4.01%]; P < .001) during the same time period. Similar results were obtained if both malignancy and suspicious for malignancy rates were considered together (15,759 [6.58%] vs 16,011 [4.98%]; P < .001). CONCLUSIONS: The data showed a persistent reduction in the cytological specimen volume during the post-lockdown period (2020). However, the relative increase in the cytological workload in the late part of the post-lockdown is a promising finding of a slow return to normality.

Reduction trend of mcr-1 circulation in Emilia-Romagna Region, Italy.

This study aims to describe trends of mcr-positive Enterobacterales in humans based on laboratory surveillance with a defined catchment population. The data source is the Micro-RER surveillance system, established in Emilia-Romagna region (Italy), to monitor the trend of mcr resistance. Enterobacterales isolates from human clinical samples with minimum inhibitory concentration (MIC) ≥ 2 mg/L for colistin were sent to the study reference laboratory for the detection of mcr genes. Isolates prospectively collected in the period 2018-2020 were considered for the assessment of population rates and trends; further analyses were carried out for the evaluation of clonality and horizontal mcr gene transfer. Previous isolates from local laboratory collection were also described. In the period 2018-2020, 1164 isolates were sent to the reference laboratory, and 51 (4.4%) were confirmed as mcr-positive: 50 mcr-1 (42 Escherichia coli, 6 Klebsiella pneumoniae, 2 Salmonella enterica) and 1 mcr-4 (Enterobacter cloacae). The number of mcr-positive isolates dropped from 24 in the first half of 2018 to 3 in the whole of 2020 (trend p value < 0.001). Genomic analyses showed the predominant role of the horizontal transfer of mcr genes through plasmids or dissemination of transposable elements compared to clonal dissemination of mcr-positive microorganisms. The study results demonstrate a substantial decrease in the circulation of mcr-1 plasmid genes in Emilia-Romagna Region.

COVID-19 and breast fine needle aspiration cytology method: What should we change?

INTRODUCTION: Air-dried slide preparation for fine needle aspiration cytology procedures is currently considered unsafe because of the risk of infectious aerosols of coronavirus 19. This study compares the safety and accuracy of two different protocols, one with and one without air-dried slides. METHODS: Starting from 3 March 2020, we discontinued the use of air-dried slides during breast fine needle aspiration procedures. We selected cases collected during two periods: 2 months before and 2 months after 3 March. In both groups, the number of procedures was recorded together with the distribution of the diagnostic categories and the concordance between cytological and histological results on surgical specimens for lesions suggestive of malignancy, using the chi-squared test. RESULTS: Of the 100 procedures performed during the pre-COVID-19 period, 55% were negative (C2), 3% were non-diagnostic (C1) and 40% were positive (C4 or C5). Of the 75 procedures obtained during the COVID-19 period, 44% were negative (C2), 2.7% were non-diagnostic (C1) and 52% were positive (C4 or C5). Despite the use of a new protocol during the COVID-19 period, we observed concordance between cytological and histological results for lesions suggestive of malignancy. There was no statistically significant difference concerning the distribution of the diagnostic categories in the two groups. CONCLUSIONS: Taking into account the slightly lower number of procedures being analysed during the COVID-19 period, the introduction of a new protocol that does not include air-dried slides is safe and reliable.

Global impact of the COVID-19 pandemic on cytopathology practice: Results from an international survey of laboratories in 23 countries.

BACKGROUND: To the authors' knowledge, the impact of the coronavirus disease 2019 (COVID-19) pandemic on cytopathology practices worldwide has not been investigated formally. In the current study, data from 41 respondents from 23 countries were reported. METHODS: Data regarding the activity of each cytopathology laboratory during 4 weeks of COVID-19 lockdown were collected and compared with those obtained during the corresponding period in 2019. The overall number and percentage of exfoliative and fine-needle aspiration cytology samples from each anatomic site were recorded. Differences in the malignancy and suspicious rates between the 2 periods were analyzed using a meta-analytical approach. RESULTS: Overall, the sample volume was lower compared with 2019 (104,319 samples vs 190,225 samples), with an average volume reduction of 45.3% (range, 0.1%-98.0%). The percentage of samples from the cervicovaginal tract, thyroid, and anorectal region was significantly reduced (P < .05). Conversely, the percentage of samples from the urinary tract, serous cavities, breast, lymph nodes, respiratory tract, salivary glands, central nervous system, gastrointestinal tract, pancreas, liver, and biliary tract increased (P < .05). An overall increase of 5.56% (95% CI, 3.77%-7.35%) in the malignancy rate in nongynecological samples during the COVID-19 pandemic was observed. When the suspicious category was included, the overall increase was 6.95% (95% CI, 4.63%-9.27%). CONCLUSIONS: The COVID-19 pandemic resulted in a drastic reduction in the total number of cytology specimens regardless of anatomic site or specimen type. The rate of malignancy increased, reflecting the prioritization of patients with cancer who were considered to be at high risk. Prospective monitoring of the effect of delays in access to health services during the lockdown period is warranted.

Next-generation sequencing-based BRCA testing on cytological specimens from ovarian cancer ascites reveals high concordance with tumour tissue analysis.

BACKGROUND: With the approval of the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib for newly diagnosed, breast cancer gene (BRCA)1/2 mutated, ovarian cancer women, the assessment of BRCA1/2 tumour status will be shortly required at the time of diagnosis. AIM: To investigate the feasibility of next-generation sequencing (NGS)-based BRCA tumour test on cytological specimens from ovarian cancer ascites. METHODS: We evaluated the BRCA1/2 status on neoplastic ascites and corresponding tumour tissue of 11 patients with ovarian cancer, using the NGS 'Oncomine BRCA Research Assay'. RESULTS: The NGS-based BRCA test on cytological samples had a success rate of 100%, with 11 of 11 concordant BRCA1/2 results between ascites and tumour tissues analyses, including two wild type samples and nine cases harbouring somatic or germline variants. CONCLUSION: BRCA test may be performed on ovarian cancer ascites, reproducing BRCA1/2 tumour status and representing a useful tool for clinical decision-making.

Endobronchial Ultrasound Transbronchial Needle Aspiration in Thoracic Diseases: Much More than Mediastinal Staging.

Background and Objective: EBUS-TBNA has revolutionized the diagnostic approach to thoracic diseases from a surgical to minimally invasive procedure. In non small-cell lung cancer (NCSLC) patients, EBUS-TBNA is able to dictate the consecutive therapy both for early and advanced stages, providing pathological diagnosis, mediastinal staging, and even adequate specimens for molecular analysis. This study reports on the ability of EBUS-TBNA to make different diagnoses and dictates the consecutive therapy in a large cohort of patients presenting different thoracic diseases. Methods: All procedures performed from January 2012 to September 2016 were reviewed. Five groups of patients were created according to the main indications for the procedure. Group 1: lung cancer staging; Group 2: pathological diagnosis in advanced stage lung cancer; Group 3: lymphadenopathy in previous malignancies; Group 4: pulmonary lesions; Group 5: unknown origin lymphadenopathy. In each group, the diagnostic yield of the procedure was analysed. Non malignant diagnosis at EBUS-TBNA was confirmed by a surgical procedure or clinical and radiological follow-up. Results: 1891 patients were included in the analysis. Sensitivity, negative predictive value, and diagnostic accuracy in each group were 90.7%, 79.4%, and 93.1% in Group 1; 98.5%, 50%, and 98.5% in Group 2; 92.4%, 85.1%, and 94.7% in Group 3; 90.9%, 51.0%, and 91.7% in Group 4; and 25%, 83.3%, and 84.2% in Group 5. Overall sensitivity, negative predictive value, and accuracy were 91.7%, 78.5%, and 93.6%, respectively. Conclusions: EBUS-TBNA is the best approach for invasive mediastinal investigation, confirming its strategic role and high accuracy in thoracic oncology.

The long tail of molecular alterations in non-small cell lung cancer: a single-institution experience of next-generation sequencing in clinical molecular diagnostics.

BACKGROUND: Molecular profiling of advanced non-small cell lung cancers (NSCLC) is essential to identify patients who may benefit from targeted treatments. In the last years, the number of potentially actionable molecular alterations has rapidly increased. Next-generation sequencing allows for the analysis of multiple genes simultaneously. AIMS: To evaluate the feasibility and the throughput of next-generation sequencing in clinical molecular diagnostics of advanced NSCLC. METHODS: A single-institution cohort of 535 non-squamous NSCLC was profiled using a next-generation sequencing panel targeting 22 actionable and cancer-related genes. RESULTS: 441 non-squamous NSCLC (82.4%) harboured at least one gene alteration, including 340 cases (63.6%) with clinically relevant molecular aberrations. Mutations have been detected in all but one gene (FGFR1) of the panel. Recurrent alterations were observed in KRAS, TP53, EGFR, STK11 and MET genes, whereas the remaining genes were mutated in <5% of the cases. Concurrent mutations were detected in 183 tumours (34.2%), mostly impairing KRAS or EGFR in association with TP53 alterations. CONCLUSIONS: The study highlights the feasibility of targeted next-generation sequencing in clinical setting. The majority of NSCLC harboured mutations in clinically relevant genes, thus identifying patients who might benefit from different targeted therapies.

Acquired Resistance to Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancers: The Role of Next-Generation Sequencing on Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Samples.

CONTEXT: - Molecular testing is essential for the diagnostic workup of patients with advanced non-small cell lung cancers. Cytology specimens from minimally invasive procedures, such as endobronchial ultrasound-guided transbronchial needle aspiration, are often the only available samples for these patients. The implementation of molecular diagnostic testing, and in particular next-generation sequencing-based testing, on these cytologic specimens is currently an evolving field for lung cytopathology. The application of these molecular analyses on tyrosine kinase inhibitor-resistant non-small cell lung cancers raises unique technical, biologic, and clinical challenges. OBJECTIVE: - To provide an overview of the implementation of next-generation sequencing analysis on endobronchial ultrasound-guided transbronchial needle aspiration samples to detect the molecular aberrations underneath the phenomenon of acquired resistance in patients with non-small cell lung cancers progressing while on the EGFR/ALK tyrosine kinase inhibitor treatment. DATA SOURCES: - Peer-reviewed original articles, review articles, and published guidelines and expert opinion reports were reviewed, together with our single-center experience. CONCLUSIONS: - Next-generation sequencing analyses and the endobronchial ultrasound-guided transbronchial needle aspiration procedure may represent a valuable strategy to address the unique requirements of molecular testing on tyrosine kinase inhibitor-resistant non-small cell lung cancers.

MicroRNA expression profile in primary lung cancer cells lines obtained by endobronchial ultrasound transbronchial needle aspiration.

BACKGROUND: Novel cancer biomarkers like microRNA (miRNA) are promising tools to gain a better understanding of lung cancer pathology and yield important information to guide therapy. In recent years, new less invasive methods for the diagnosis and staging of NSCLC have become key tools in thoracic oncology and the worldwide spread of endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA). However, appropriate specimen handling is mandatory to achieve adequate results and reproducibility. The aim of this single centre prospective study was to evaluate the feasibility of a complete miRNA expression profile in fresh NSCLC cell lines obtained by EBUS-TBNA. METHODS: Patients with proven NSCLC underwent EBUS-TBNA for the diagnosis of suspect lymph node metastasis, and cytological specimens were collected for epithelial cell culture and miRNA expression analysis. To validate the miRNA expression profile, we compared the results from EBUS-TBNA NSCLC specimens with those obtained from formalin-fixed paraffin-embedded (FFPE) mediastinoscopy specimens. RESULTS: Analysis of the miRNA expression profiles of three independent EBUS-TBNA-derived primary cell lines allowed the screening of 377 different human miRNAs. One hundred and fifty miRNAs were detected in all cell lines. Analysis of the miRNA expression profile in mediastinoscopy specimens showed a strong similarity in the clusters analysed. CONCLUSIONS: The miRNA expression profile is feasible and reliable in EBUS-TBNA specimens. Validation of this protocol in fresh cytological specimens represents an effective and reproducible method to correlate translational and clinical research.

EBUS-TBNA in PET-positive lymphadenopathies in treated cancer patients.

Mediastinal lymph node enlargement is common in the follow-up of patients with previously treated malignancies. The aim of this study is to assess the role of endobronchial ultrasound (EBUS) transbronchial needle aspiration (TBNA) for cyto-histological evaluation of positron emission tomography with 18fluorodeoxyglucose (PET) positive mediastinal and hilar lymph nodes developed in patients with previous malignancies. All EBUS-TBNA cases performed from January 2012 to May 2016 were retrospective reviewed. Results of EBUS-TBNA in patients with mediastinal and/or hilar lymphadenopathies were analysed. Non-malignant cytopathologies were confirmed with surgical procedures or clinical and radiological follow-up. Among 1780 patients, 176 were included in the analysis. 103 of these (58.5%) had a diagnosis of tumour recurrence whereas 73 (41.5%) had a different diagnosis: 63 (35.8%) had a non-neoplastic diagnosis and 8 patients (4.6%) had a different cell type malignancy. Samples were false-negative in 5 (2.8%) out of 176 patients. The overall sensitivity, specificity, negative predicted value and diagnostic accuracy were 95.7% (95% CI 90.2-98.6%), 100% (95% CI 94.0-100%), 92.3% (95% CI 83.2-96.7%) and 97.2% (95% CI 93.5-98.8%), respectively. EBUS-TBNA demonstrated a pathological diagnosis different from the previous tumour in a large percentage of patients, confirming its strategic role in the management of patients with previously treated malignancies.

Autophagy regulates UBC9 levels during viral-mediated tumorigenesis.

UBC9, the sole E2-conjugating enzyme required for SUMOylation, is a key regulator of essential cellular functions and, as such, is frequently altered in cancers. Along these lines, we recently reported that its expression gradually increases during early stages of human papillomavirus (HPV)-mediated cervical lesions transformation. However, a better understanding of how UBC9 is exploited by transforming viral oncoproteins is still needed. In the present study, we show that in human samples HPV drives UBC9 up-regulation also in very early steps of head and neck tumorigenesis, pointing to the important role for UBC9 in the HPV-mediated carcinogenic program. Moreover, using HPV-infected pre-cancerous tissues and primary human keratinocytes as the natural host of the virus, we investigate the pathological meaning and the cellular mechanisms responsible for UBC9 de-regulation in an oncoviral context. Our results show that UBC9 overexpression is promoted by transforming viral proteins to increase host cells' resistance to apoptosis. In addition, ultrastuctural, pharmacological and genetic approaches crucially unveil that UBC9 is physiologically targeted by autophagy in human cells. However, the presence of HPV E6/E7 oncoproteins negatively impacts the autophagic process through selective inhibition of autophagosome-lysosome fusion, finally leading to p53 dependent UBC9 accumulation during viral-induced cellular transformation. Therefore, our study elucidates how UBC9 is manipulated by HPV oncoproteins, details the physiological mechanism by which UBC9 is degraded in cells, and identifies how HPV E6/E7 impact on autophagy. These findings point to UBC9 and autophagy as novel hallmarks of HPV oncogenesis, and open innovative avenues towards the treatment of HPV-related malignancies.

Prevalence and Risk Factors of Human Papillomavirus Infection in 18-Year-Old Women: Baseline Report of a Prospective Study on Human Papillomavirus Vaccine.

OBJECTIVES: Little is known about the epidemiology of human papillomavirus (HPV) in Italy before the age of 25. At the European Institute of Oncology, a prospective observational study on cervical HPV infection in 18-year-old women undergoing quadrivalent HPV vaccination is ongoing. METHODS: At the first visit before vaccination, all the young women answered an epidemiological questionnaire, and then, the presence of high-risk HPV (hrHPV) was tested. Samples positive for hrHPV were genotyped. Liquid-based cytology was done only to women declaring not to be virgins. Any positivity at cytology or HPV testing was completed with colposcopy and eventually biopsies. RESULTS: Seven hundred and thirty women were enrolled. Two hundred sixty-six women were virgins; 7 (2.6%) of these resulted positive to hrHPV: 1 had HPV16 and CP6108, whereas the other 6 resulted negative at genotyping. Of the 464 nonvirgins, 61 (13.1%) were HPV positive: 19 had HPV16, 4 were positive to HPV18 with other hrHPVs, 25 to other hrHPVs, 7 to low-risk HPV, whereas 13 resulted negative at genotyping. HPV positivity was significantly associated to both smoking and having more than 3 partners. Cervical cytology was negative in 433 cases (93.3%), ASC-US in 10 cases (2.2%), low-grade squamous intraepithelial lesion in 20 cases (4.3%), and ASC-H in 1 case (0.2%). No CIN2+ was identified. CONCLUSIONS: Overall, we found a low positivity to HPV in this population; however, the rate of HPV positivity was significantly related to smoking and sexual life. The cytology result low-grade squamous intraepithelial lesion was more frequent than in the screening population, whereas no CIN2+ was identified, confirming the indication to avoid screening at this age.

Successful palliative approach with high-intensity focused ultrasound in a patient with metastatic anaplastic pancreatic carcinoma: a case report.

We report a case of a 74-year-old man with a metastatic anaplastic pancreatic carcinoma (APC). After an early tumour progression on first-line chemotherapy with cisplatin and gemcitabine, even though it was badly tolerated, he was treated with a combination of systemic modified FOLFIRI and high-intensity focused ultrasound (HIFU) on the pancreatic mass. A tumour showing partial response with a clinical benefit was obtained. HIFU was preferred to radiotherapy because of its shorter course and minimal side effects, in order to improve the patient's clinical conditions. The patient is currently on chemotherapy, asymptomatic with a good performance status. In referral centres, with specific expertise, HIFU could be safely and successfully combined with systemic chemotherapy for treatment of metastatic pancreatic carcinoma.

Molecular Testing for Targeted Therapy in Advanced Non-Small Cell Lung Cancer: Suitability of Endobronchial Ultrasound Transbronchial Needle Aspiration.

OBJECTIVES: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive procedure that has revolutionized the diagnosis and staging of lung cancer. The goal of the present study was to investigate the yield and applicability of molecular testing in the specimens obtained by EBUS-TBNA from patients with advanced non-small cell lung cancer (NSCLC), comparing the results with a series of patients who underwent diagnostic surgical procedures in the same institution. METHODS: The study followed 306 consecutive patients with clinically diagnosed primary lung cancer who had the EBUS-TBNA procedure. EGFR and KRAS mutations were evaluated on cytologic specimens by Sanger sequencing and Cobas real-time polymerase chain reaction, whereas ALK rearrangement was tested by fluorescence in situ hybridization. The results were compared with those obtained from a series of 1,000 NSCLC surgical samples routinely analyzed. RESULTS: Molecular testing was possible in 96.9% of the samples obtained by EBUS-TBNA. EGFR (exons 18-21) mutations were found in 16.9%, KRAS mutation (exons 2-3) in 31.6%, and ALK rearrangement in 3.9% of the cases. In the surgical series, the mutations' distribution were 14.8%, 29.0%, and 3.4%, respectively. There were no statistical differences between the two series. CONCLUSIONS: Our study demonstrates that EBUS-TBNA can be effectively used not just for diagnosis but also for complete mutational testing.

The predictive value of human papillomavirus testing for the outcome of patients conservatively treated for stage IA squamous cell cervical carcinoma.

BACKGROUND: Although it is hypothesised that human papillomavirus (HPV) testing may have a role in surveillance of patients conservatively treated for stage IA squamous cell cervical carcinoma, research on this topic has been minimal. OBJECTIVES: To determine: (1) the changes in HPV test result from treatment onward; (2) the time to viral clearance; and (3) the negative predictive value (NPV) and positive predictive value (PPV) of HPV test result for the detection of CIN2 or worse (CIN2+) during follow-up. STUDY DESIGN: In a multicentre retrospective follow-up study of a consecutive series (1997-2009) of 91 patients, longitudinal outcome measures were estimated as cumulative probabilities using the Kaplan-Meier method. RESULTS: For patients testing HPV-positive at the first follow-up visit (n=44), the probability of change to negative rose from 0 to 0.78 between 7 and 21 months after treatment. For HPV-negative patients (n=47), the probability of change to positive rose to 0.13 between 9 and 26 months. After a median follow-up of 50 months (range, 2-80), the NPV for CIN2+ was 1.00. The PPV was 0.60 (95% confidence interval, 0.43-0.77) after 26 months. The median time to detection was 5 months. CONCLUSIONS: If adequately confirmed, these findings would indicate that HPV testing is capable to identify the patients who have had their lesions fully removed, and would make it possible to focus follow-up efforts on a subset of patients at high risk of residual or progressive disease.

The SUMO conjugating enzyme UBC9 as a biomarker for cervical HPV infections.

Human papillomaviruses (HPVs) infect stratified epithelium and are the causative agents of cervical cancer, the second most common cause of cancer-related death in women. A critical aspect that still persists in the HPV field is the selection of very sensitive and specific HPV diagnostic assays. Here, we provide evidence that the crucial small ubiquitin-like modifier (SUMO) E2-conjugating enzyme Ubc9 is strongly upregulated in cervical lesions. Ubc9 detection could thus be used in diagnosing and/or monitoring the progression of an HPV oncogenic infection.