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1. Contemporary antithrombotic strategies in patients with acute coronary syndromes managed without revascularization: insights from the EYESHOT study

Author

De Luca, Leonardo, Leonardi, Sergio, Smecca, Ignazio Maria, Formigli, Dario, Lucci, Donata, Gonzini, Lucio, Tuccillo, Bernardino, Olivari, Zoran, Gulizia, Michele Massimo, Bovenzi, Francesco Maria, De Servi, Stefano, Caporale, R., Cavallini, C., Ceravolo, R., Lupi, A., Musumeci, G., Rakar, S., Maggioni, A. P., Lorimer, A., Orsini, G., Fabbri, Giorgio, Bianchini, E., Abrignani, M. G., Bonura, F., Trimarco, B., Galasso, Giorgia, Misuraca, G., Manes, M. T., Irace, Lorenzo, Totis, O., Ledda, A., Mauro, C., Boccalatte, M., Iliceto, S., Cacciavillani, L., Savonitto, S., Tortorella, G., Esposito, L., DE ROSA, Paolo, Calabrò, P., Bianchi, R., Napoletano, C., Lalla Piccioni, L., Pavesi, P. C., Boni, Allegra, Merenda, R., Wolff, S., De Ferrari, G. M., Camporotondo, R., Gambino, Paolo, Cutaia, A., Picariello, C., Cemin, R., Chiarella, F., Grazioli Gauthier, L., Mircoli, L., Del Pinto, M., Finocchiaro, M. L., Scioli, R., Farina, R., Naddeo, C., Scherillo, M., Santopietro, S., Metra, M., Costa, F., Calculli, G., Troito, G., Pennisi, V., Adornato, E. M. F., Pirelli, S., Fadin, B. M., Di Biase, M., Ieva, R., Zuin, G., Sanfilippo, N., Mancuso, LAURA CATERINA, Pani, Luisa Anna, Serra, Eleonora, Marenzi, G., Assanelli, E. M., Ansalone, G., Cacciotti, L., Morocutti, G., Fresco, C., Berti, S., Paradossi, U., Bozzano, A., Mauro, A., Noussan, P., Zanini, P., Bolognese, L., Falsini, G., Costa, P., Manca, G., Caldarola, P., Locuratolo, N., Cipolla, T., Becchina, M., Cocco, Gabriele, Scalera, G., Stefanelli, S., Giunta, N., Sinagra, G., Meloni, L., Lai, O., Chiaranda, G., Luca, G., Sleiman Helou, J., Biscottini, E., Magliari, F., Callerame, M., Uguccioni, M., Pugliese, M., Sanchez, F., Tartaglione, S., Ignone, G., Mavilio, G., Mantovan, R., Bini, R., Caico, S. I., Demolli, V., Proietti, F., Michisanti, M., Musmeci, G., Cantamessa, P., Sicuso, G., Micalef, S. S., Accogli, M., Zaccaria, MICHELA MARIA, Caputo, M., Di Paolo, G., Piatti, L., Farina, A., Vicinelli, P., Paloscia, L., Di Clemente, D., Felis, S., Castini, D., Rota, C., Casu, Gabriella, Bonano, S., Margheri, M., Ricci Lucchi, G., Serdoz, R., Proietti, P., Autore, C., Conti, E., Russo, V., Orlando, P., Ramondo, A. B., Bontorin, M., Marcolongo, M., Marrara, F., Maestroni, A., Vitti, P., Rodella, P., Bonetti, P., Elia, M., Lumare, R., Politi, A., Gritti, S., Poletti, F., Mafrici, A., Fusco, R., Bongo, A. S., Bacchini, S., Gasparetto, V., Ferraiuolo, G., Campana, C., Bonatti, R., Gaita, F., Bergerone, S., Bonmassari, R., Zeni, P., Langialonga, T., Scarcia, A., Caravita, L., Musacchio, E., Augello, G., Usmiani, T., Stomaci, B., Cirino, D., Pierini, S., Bottiglieri, G., Liso, A., Mussardo, M., Tosi, P., Sala, R., Belloni, A., Blengino, S., Lisi, E., Delfino, P., Auguadro, C., Brunazzi, M. C., Pacchioni, E., Fattore, L., Bosco, B., Blandizzi, S., Pajes, G., Patruno, N., Perna, G. P., Francioni, M., Favale, S., Vestito, D., Lombardi, A., Capecchi, A., Ferrero, P., De Vincenzo, C., Magri, G., Indolfi, C., De Rosa, S., Rossi, M., Collarini, L., Agnelli, D., Conti, G., Tonelli, C., Spadaro, C., Negroni, S., Di Noto, G., Lanari, A., Casolo, G., Del Meglio, J., Negrini, M., Celentano, A., Sifola, C., Rellini, G., Della Mattia, A., Molero, U., Piovaccari, G., Grosseto, D., Callegarin, L., Fiasconaro, G., Crivello, R., Thiebat, B., Leone, G., Tamburino, C., Caruso, G., Cassadonte, F., Sassone, B., Fuca, G., Sormani, L., Percoco, G. F., Mazzucco, R., Cazzani, E., Gianni, M., Limido, A., Luvini, M., Guglielmi, R., Mannarini, A., Moruzzi, P., Pastori, P., Golia, B., Marzano, A., Orazi, S., Marchese, I., Anselmi, M., Girardi, P., Nassiacos, D., Meloni, S., Busacca, P., Generali, C. A., Corda, S., Costanza, G., Montalto, S., Argenziano, L., Tommasini, P., Emdin, M., Pasanisi, E. M., Colivicchi, F., Tubaro, M., Azzolini, P., Luciani, C., Doronzo, B., Coppolino, A., Dellavesa, P., Zenone, F., Di Marco, A., De Conti, F., Piccinni, G. C., Gualtieri, M. R., Bisignani, G., Leone, A., Arcuri, G. M., Marinacci, L., Rossi, P., Perotti, S., Cotti Cometti, V., Arcidiacono, S., Tramontana, M., Bazzucchi, M., Mezzetti, P., Romano, M., Villani, R., Di Giovambattista, R., Volpe, B., Tedesco, L., Carini, M., Vinci, S., Paolini, E. A., Busoni, F., Piergentili, C., Navazio, A., Manca, F., Cocco, F., Pennetta, C. A., Maggiolini, S., Galbiati, R., Bruna, C., Ferrero, L., Brigido, S., Barducci, E., Musacchio, D., Manduca, B., Marchese, D., Patrassi, L. A., Pattarino, F. A., Rocchi, M., Briglia, S., Fanelli, R., Villella, M., Gronda, E., Massa, D., Lenti, V., Di Gregorio, L., Bottero, M., Bazzanini, F., Braggion, G., Antoniceli, R., Caraceni, D., Guzzo, V., Di Giovanni, P., Scarpini, S., Severgnini, B., Musolino, M. F., Della Casa, S., Gobbi, M., Arena, G., Bonizzato, S., Agnoletto, V., Sansoni, S., Pes, R. A. M., Denti, S., Polizzi, G. M., Pino, R., Commisso, B., Merlino, A., Di Lorenzo, L., Porchetta, I., Del Furia, F., Colombi, E., Covini, D., Cavalieri, F., Antonaci, S., Rubino, G., Ciulla, A., Bui, F., Casorelli, E., Caliendo, L., Laezza, A., Americo, L., Schillaci, A. M., Cordoni, M., Barsotti, L., Gaudio, C., Barilla, F., Cannone, M., Memeo, R., Truncellito, L., Andriani, A., Salituri, S., Verrina, F., Pafi, M., Sebastiani, M. L., Amico, A. F., Scolozzi, D., D'Alea, A., Catanzariti, D., Angheben, C., Ottaviano, A., and Levantesi, G.

Subjects
Male, Ticagrelor, medicine.medical_specialty, Acute coronary syndrome, medicine.medical_treatment, Conservative strategy, Population, Acute coronary syndromes, Revascularization, acute coronary syndromes, anticoagulant, antithrombotic therapy, conservative strategy, prasugrel, ticagrelor, aged, coronary care units, female, fibrinolytic agents, follow-up studies, hospital mortality, humans, iItaly, length of stay, male, myocardial revascularization, retrospective studies, survival rate, thrombolytic therapy, practice guidelines as topic, Fibrinolytic Agents, Anticoagulant, Antithrombotic therapy, Prasugrel, Acute Coronary Syndrome, Aged, Coronary Care Units, Female, Follow-Up Studies, Hospital Mortality, Humans, Italy, Length of Stay, Myocardial Revascularization, Retrospective Studies, Survival Rate, Thrombolytic Therapy, Practice Guidelines as Topic, Cardiology and Cardiovascular Medicine, Pharmacology (medical), Internal medicine, Antithrombotic, medicine, education, Survival rate, education.field_of_study, business.industry, Clopidogrel, medicine.disease, Cardiology, business, Fibrinolytic agent, medicine.drug
Abstract

Aims Patients with acute coronary syndromes (ACSs) who are managed without coronary revascularization represent a mixed and understudied population that seems to receive suboptimal pharmacological treatment. Methods and results We assessed patterns of antithrombotic therapies employed during the hospitalization and in-hospital clinical events of medically managed patients with ACS enrolled in the prospective, multicentre, nationwide EYESHOT (EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units) registry. Among the 2585 consecutive ACS patients enrolled in EYESHOT, 783 (30.3%) did not receive any revascularization during hospital admission. Of these, 478 (61.0%) underwent coronary angiography (CA), whereas 305 (39.0%) did not. The median GRACE and CRUSADE risk scores were significantly higher among patients who did not undergo CA compared with those who did (180 vs. 145, P < 0.0001 and 50 vs. 33, P < 0.0001, respectively). Antithrombotic therapies employed during hospitalization significantly differ between patients who received CA and those who did not with unfractioned heparin and novel P2Y12 inhibitors more frequently used in the first group, and low-molecular-weight heparins and clopidogrel in the latter group. During the index hospitalization, patients who did not receive CA presented a higher incidence of ischaemic cerebrovascular events and of mortality compared with those who underwent CA (1.6 vs. 0.2%, P = 0.04 and 7.9 vs. 2.7%, P = 0.0009, respectively). Conclusion Almost one-third of ACS patients are managed without revascularization during the index hospitalization. In this population, a lower use of recommended antiplatelet therapy and worse clinical outcome were observed in those who did not undergo CA when compared with those who did. Clinical Trial Registration Unique identifier: [NCT02015624][1], . [10.1093/ehjcvp/pvv017][2] [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02015624&atom=%2Fehjcardpharm%2F1%2F3%2F168.atom [2]: /lookup/doi/10.1093/ehjcvp/pvv017

Published
2015
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2. Antithrombotic strategies in the catheterization laboratory for patients with acute coronary syndromes undergoing percutaneous coronary interventions: insights from the EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units Registry

Author

De Luca, L., Musumeci, G., Leonardi, S., Gonzini, L., Cavallini, C., Calabro, P., Mauro, C., Cacciavillani, L., Savonitto, S., De Servi, S., Caporale, R., Ceravolo, R., Formigli, D., Lupi, A., Rakar, S., Smecca, I. M., Maggioni, A. P., Lucci, D., Lorimer, A., Orsini, G., Fabbri, G., Bianchini, E., Abrignani, M. G., Bonura, F., Trimarco, B., Galasso, G., Misuraca, G., Manes, M. T., Tuccillo, B., Irace, L., Olivari, Z., Totis, O., Ledda, A., Boccalatte, M., Iliceto, S., Tortorella, G., Esposito, L., De Rosa, P., Bianchi, R., Napoletano, C., Piccioni, L. L., Pavesi, P. C., Bovenzi, F. M., Boni, A., Merenda, R., Wolff, S., De Ferrari, G. M., Camporotondo, R., Gambino, P., Cutaia, A., Picariello, C., Cemin, R., Chiarella, F., Gauthier, L. G., Mircoli, L., Del Pinto, M., Finocchiaro, M. L., Scioli, R., Farina, R., Naddeo, C., Scherillo, M., Santopietro, S., Metra, M., Costa, F., Calculli, G., Troito, G., Pennisi, V., Adornato, E. M. F., Pirelli, S., Fadin, B. M., DI Biase, M., Ieva, R., Zuin, G., Sanfilippo, N., Mancuso, L., Pani, A., Serra, E., Marenzi, G., Assanelli, E. M., Ansalone, G., Cacciotti, L., Morocutti, G., Fresco, C., Berti, S., Paradossi, U., Bozzano, A., Mauro, A., Noussan, P., Zanini, P., Bolognese, L., Falsini, G., Costa, P., Manca, G., Caldarola, P., Locuratolo, N., Cipolla, T., Becchina, M., Cocco, G., Scalera, G., Stefanelli, S., Giunta, N., Sinagra, G., Meloni, L., Lai, O., Chiaranda, G., Luca, G., Helou, J. S., Biscottini, E., Magliari, F., Callerame, M., Uguccioni, M., Pugliese, M., Sanchez, F., Tartaglione, S., Ignone, G., Mavilio, G., Mantovan, R., Bini, R., Caico, S. I., Demolli, V., Proietti, F., Michisanti, M., Musmeci, G., Cantamessa, P., Sicuso, G., Micalef, S. S., Accogli, M., Zaccaria, M., Caputo, M., DI Paolo, G., Piatti, L., Farina, A., Vicinelli, P., Paloscia, L., DI Clemente, D., Felis, S., Castini, D., Rota, C., Casu, G., Bonano, S., Margheri, M., Lucchi, G. R., Serdoz, R., Proietti, P., Autore, C., Conti, E., Russo, V., Orlando, P., Ramondo, A. B., Bontorin, M., Marcolongo, M., Santagostino, M., Maestroni, A., Vitti, P., Rodella, P., Bonetti, P., Elia, M., Lumare, R., Politi, A., Gritti, S., Poletti, F., Mafrici, A., Fusco, R., Bongo, A. S., Bacchini, S., Gasparetto, V., Ferraiuolo, G., De Luca, M., Campana, C., Bonatti, R., Gaita, F., Bergerone, S., Bonmassari, R., Zeni, P., Langialonga, T., Scarcia, A., Caravita, L., Musacchio, E., Augello, G., Usmiani, T., Stomaci, B., Cirino, D., Pierini, S., Bottiglieri, G., Liso, A., Mussardo, M., Tosi, P., Sala, R., Belloni, A., Blengino, S., Lisi, E., Delfino, P., Auguadro, C., Brunazzi, M. C., Pacchioni, E., Fattore, L., Bosco, B., Blandizzi, S., Pajes, G., Patruno, N., Perna, G. P., Francioni, M., Favale, S., Vestito, D., Lombardi, A., Capecchi, A., Ferrero, P., De Vincenzo, C., Magri, G., Indolfi, C., De Rosa, S., Rossi, M., Collarini, L., Agnelli, D., Conti, G., Tonelli, C., Spadaro, C., Negroni, S., DI Noto, G., Lanari, A., Casolo, G., Del Meglio, J., Negrini, M., Celentano, A., Sifola, C., Rellini, G., Mattia, A. D., Molero, U., Piovaccari, G., Grosseto, D., Callegarin, L., Fiasconaro, G., Crivello, R., Thiebat, B., Leone, G., Tamburino, C., Caruso, G., Cassadonte, F., Sassone, B., Fuca, G., Sormani, L., Percoco, G. F., Mazzucco, R., Cazzani, E., Gianni, M., Limido, A., Luvini, M., Guglielmi, R., Mannarini, A., Moruzzi, P., Pastori, P., Golia, B., Marzano, A., Orazi, S., Marchese, I., Anselmi, M., Girardi, P., Nassiacos, D., Meloni, S., Busacca, P., Generali, C. A., Corda, S., Costanza, G., Montalto, S., Argenziano, L., Tommasini, P., Emdin, M., Pasanisi, E. M., Colivicchi, F., Tubaro, M., Azzolini, P., Luciani, C., Doronzo, B., Coppolino, A., Dellavesa, P., Zenone, F., DI Marco, A., De Conti, F., Piccinni, G. C., Gualtieri, M. R., Bisignani, G., Leone, A., Arcuri, G. M., Marinacci, L., Rossi, P., Perotti, S., Cometti, V. C., Arcidiacono, S., Tramontana, M., Bazzucchi, M., Mezzetti, P., Romano, M., Villani, R., DI Giovambattista, R., Volpe, B., Tedesco, L., Carini, M., Vinci, S., Paolini, E. A., Busoni, F., Piergentili, C., Navazio, A., Manca, F., Cocco, F., Pennetta, C. A., Maggiolini, S., Galbiati, R., Bruna, C., Ferrero, L., Brigido, S., Barducci, E., Musacchio, D., Manduca, B., Marchese, D., Patrassi, L. A., Pattarino, F. A., Rocchi, M., Briglia, S., Fanelli, R., Villella, M., Gronda, E., Massa, D., Lenti, V., DI Gregorio, L., Bottero, M., Bazzanini, F., Braggion, G., Antoniceli, R., Caraceni, D., Guzzo, V., DI Giovanni, P., Scarpini, S., Severgnini, B., Musolino, M. F., Casa, S. D., Gobbi, M., Arena, G., Bonizzato, S., Agnoletto, V., Sansoni, S., Pes, R. A. M., Denti, S., Polizzi, G. M., Pino, R., Commisso, B., Merlino, A., DI Lorenzo, L., Porchetta, I., Del Furia, F., Colombi, E., Covini, D., Cavalieri, F., Antonaci, S., Rubino, G., Ciulla, A., Bui, F., Casorelli, E., Caliendo, L., Laezza, A., Americo, L., Schillaci, A. M., Cordoni, M., Barsotti, L., Gaudio, C., Barilla, F., Cannone, M., Memeo, R., Truncellito, L., Andriani, A., Salituri, S., Verrina, F., Pafi, M., Sebastiani, M. L., Amico, A. F., Scolozzi, D., Lupi, G., D'Alea, A., Catanzariti, D., Angheben, C., Ottaviano, A., Levantesi, G., de Luca, Leonardo, Musumeci, Giuseppe, Leonardi, Sergio, Gonzini, Lucio, Cavallini, Claudio, Calabrò, Paolo, Mauro, Ciro, Cacciavillani, Luisa, Savonitto, Stefano, de Servi, Stefano, Caporale, Roberto, Ceravolo, Roberto, Formigli, Dario, Lupi, Alessandro, Rakar, Sadir, Smecca, Ivan, Maggioni, Aldo Pietro, Lucci, Donata, Lorimer, Andrea, Orsini, Giampietro, Fabbri, Gianna, Bianchini, Elisa, Abrignani, Maurizio Giuseppe, Bonura, Francesc, Trimarco, Bruno, Galasso, Gennaro, Misuraca, Gianfranco, Manes, Maria Teresa, Tuccillo, Bernardino, and Irace, Luigi.

Subjects
Male, Prasugrel, medicine.medical_treatment, Myocardial Infarction, antithrombotic therapy, 030204 cardiovascular system & hematology, acute coronary syndromes, bivalirudin, heparins, percutaneous coronary intervention, prasugrel, ticagrelor, 0302 clinical medicine, Antithrombotic, 80 and over, Bivalirudin, 030212 general & internal medicine, Myocardial infarction, Prospective Studies, Registries, Aged, 80 and over, General Medicine, Hirudins, Middle Aged, Recombinant Proteins, Italy, Female, Cardiology and Cardiovascular Medicine, Ticagrelor, medicine.drug, medicine.medical_specialty, Platelet Glycoprotein GPIIb-IIIa Complex, NO, 03 medical and health sciences, Percutaneous Coronary Intervention, Internal medicine, medicine, Humans, Acute Coronary Syndrome, Aged, Aspirin, business.industry, Heparin, Percutaneous coronary intervention, Anticoagulants, medicine.disease, Peptide Fragments, Clinical trial, Cross-Sectional Studies, Logistic Models, Conventional PCI, Multivariate Analysis, business
Abstract

Aims In the last decades, several new therapies have emerged for the treatment of acute coronary syndromes (ACS). We sought to describe real-world patterns of use of antithrombotic treatments in the catheterization laboratory for ACS patients undergoing percutaneous coronary interventions (PCI). Methods EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units was a nationwide, prospective registry aimed to evaluate antithrombotic strategies employed in ACS patients in Italy. Results Over a 3-week period, a total of 2585 consecutive ACS patients have been enrolled in 203 cardiac care units across Italy. Among these patients, 1755 underwent PCI (923 with ST-elevation myocardial infarction and 832 with non-ST-elevation ACS). In the catheterization laboratory, unfractioned heparin was the most used antithrombotic drug in both ST-elevation myocardial infarction (64.7%) and non-ST-elevation ACS (77.5%) undergoing PCI and, as aspirin, bivalirudin and glycoprotein IIb/IIIa inhibitors (GPIs) more frequently employed before or during PCI compared with the postprocedural period. Any crossover of heparin therapy occurred in 36.0% of cases, whereas switching from one P2Y12 inhibitor to another occurred in 3.7% of patients. Multivariable analysis yielded several independent predictors of GPIs and of bivalirudin use in the catheterization laboratory, mainly related to clinical presentation, PCI complexity and presence of complications during the procedure. Conclusion In our contemporary, nationwide, all-comers cohort of ACS patients undergoing PCI, antithrombotic therapies were commonly initiated before the catheterization laboratory. In the periprocedural period, the most frequently employed drugs were unfractioned heparin, leading to a high rate of crossover, followed by GPIs and bivalirudin, mainly used during complex PCI. Clinical trial registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02015624.

Published
2017

3. Comparison of the conventional cervical smear and liquid-based cytology: Results of a controlled, prospective study in the Abruzzo Region of Italy

Author

Maccallini, V., Angeloni, C., Caraceni, D., Fortunato, C., Venditti, M. A., Di Gabriele, G., Antonelli, C., Lattanzi, A., Puliti, D., Ciatto, S., Confortini, M., CRISTINA SANI, and Zappa, M.

Subjects
Adult, Vaginal Smears, liquid-based cytology, papanicolaou smear, uterine cervical cancer, Cost-Benefit Analysis, Cytological Techniques, Humans, Uterine Cervical Neoplasms, Female, Prospective Studies, Middle Aged
Abstract

To compare conventional cervical testing (CCT) and liquid-based cytology (LBC) within a randomized trial performed during 2001-2002 in the Abruzzo Region of Italy, including a cost-outcome comparative analysis.Study subjects were recruited in the framework of a controlled, randomized study organized in the Abruzzo Region. Women aged 2 6-64 years were randomized to an active arm (LBC) or control arm (CC1). The particip ating laboratories had no previous ex perience with LBC.The inadequacy rate was 4.3% in CCT and 1.3% in the LBC arm (D0.001). Atypical squamous cells of undetermined sign ifi cance and atypical glands of undetermined significance reports were more frequent at CCT vs. LBC. A small, insignificant excess of low grade squamous intraepithelial lesions or high grade squamous epithelial lesions+ reports was observed in the LBC arm. The cervical intraepithelial neoplasia 2+ (CIN2+) detection rate was not statistically different in the 2 arms (CCT=0.54%, LBC= 0.66%, p = 0.28). In the overall series positive predictive value was slightly but not significantly higher in the LBC arm. LBC increased costs by 4.2% per both screened women and CIN2+ detected.The study reflects the introductory phase of LBC in laboratories without prior LBC experience. In this setting LBC reduced the inadequacy rate and decreased reading and was at least as sensitive as and more specific than CCT. Utilization of LBC in organized screening programs will be based on local feasibility, considering that the high cost of LBC is only partially compensated for by other benefits, such as residual cellular material, available for molecular testing, including human papillomavirus testing.

Published
2008

4. Comparison of oncogenic HPV type-specific viral DNA load and E6/E7 mRNA detection in cervical samples: Results from a multicenter study

Author

Philippe Halfon, Sandra Rosini, Roberta Zappacosta, Mauro S. Malnati, Lucia Ciccocioppo, Francesco Broccolo, B Matteoli, Luca Ceccherini-Nelli, Lisa Fusetti, Donatella Caraceni, Broccolo, F, Fusetti, L, Rosini, S, Caraceni, D, Zappacosta, R, Ciccocioppo, L, Matteoli, B, Halfon, P, Malnati, M, and Ceccherini Nelli, L

Subjects
Adult, Genotype, Sequence analysis, Uterine Cervical Neoplasms, Biology, Real-Time Polymerase Chain Reaction, Cervical intraepithelial neoplasia, Sensitivity and Specificity, Young Adult, chemistry.chemical_compound, HPV, viral load, Predictive Value of Tests, Virology, medicine, Humans, E6/E7 mRNA detection, RNA, Messenger, HPV DNA load, Papillomaviridae, Aged, Retrospective Studies, Cervical cancer, Messenger RNA, Papillomavirus Infections, virus diseases, Sequence Analysis, DNA, Middle Aged, Oncogenic HPV, medicine.disease, Molecular biology, Multicenter study, Infectious Diseases, Molecular Diagnostic Techniques, chemistry, Predictive value of tests, DNA, Viral, Cervical samples, RNA, Viral, Female, Viral load, DNA
Abstract

High-risk human papillomavirus (HR-HPV) genotype viral load and E6/E7 mRNA detection are proposed as surrogate markers of malignant cervical lesion progression. Currently, the use of commercially available DNA-based or mRNA-based tests is under investigation. In this study, the viral DNA load and E6/E7 mRNA detection of the five most common HR-HPV types detected in cervical cancer worldwide were compared in 308 cervical samples by using in-house type-specific quantitative real-time PCR assays and PreTect HPV-Proofer test, respectively. Sensitivity and negative predictive values were higher for the HPV-DNA assays combined (95.0% and 96.0%, respectively) than the RNA assays (77.0% and 88.0%, respectively); conversely, the mRNA test showed a higher specificity and higher positive predictive value (81.7% and 66.9%, respectively) than the DNA test (58.6% and 52.5%, respectively) for detecting histology-confirmed high-grade cervical intraepithelial neoplasia. A significantly higher association between viral DNA load and severity of disease was observed for HPV 16 and 31 (γ = 0.62 and γ = 0.40, respectively) than for the other HPV types screened. A good degree of association between the two assays was found for detection of HPV 16 (k = 0.83), HPV 18 (k = 0.72), HPV 33 (k = 0.66), and HPV 45 (k = 0.60) but not for HPV 31 (k = 0.24). Sequence analysis in L1 and E6-LCR regions of HPV 31 genotypes showed a high level of intra-type variation. HR-HPV viral DNA load was significantly higher in E6/E7 mRNA positive than negative samples (P < 0.001), except for HPV 31. These findings suggest that transcriptional and replicative activities can coexist within the same sample

Published
2012
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