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HPV detection in patients with atypical squamous cells diagnosis in a Mexican population. Comparison of HC2 and PCR tests
Detección de VPH en pacientes con diagnóstico de células escamosas atípicas en una población mexicana. Comparación entre las pruebas HC2 y PCR
Hallmann Rita Sotelo-Regila, Marcela Lizano-Soberónb, Adela Carrillo-Garcíab, Itzel Saldaña-Santamaríaa, Alejandro García-Carrancáb, Margarita Ibarra-del Ríoa, Lorena Flores-Hernándeza
a Departamento de Citopatología, Instituto Nacional de Cancerología, México.
b Unidad de Investigación Biomédica en Cáncer. Instituto Nacional de Cancerología, México and Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México.
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    "textoCompleto" => "<span class="elsevierStyleBold">¿ INTRODUCTION</span> <p class="elsevierStylePara">Cancer of the uterine cervix affects nearly 500 000 women worldwide&#59;<span class="elsevierStyleSup">1</span> Mexico has one of the highest incidence &#40;40 &#215; 100 000 females&#41;<span class="elsevierStyleSup">2</span> and mortality rates &#40;17 &#215; 100 000 inhabitants&#41; for this type of cancer&#46;<span class="elsevierStyleSup">3</span> It has been demonstrated that more than 90&#37; of cervical carcinomas are associated with persistent infections of oncogenic genotypes of the human papillomavirus &#40;HPV&#41;&#44; mainly types 16 and 18&#46;<span class="elsevierStyleSup">4</span></p> <p class="elsevierStylePara">Despite that intensive early-detection campaigns have been conducted in Mexico for more than 30 years&#44;<span class="elsevierStyleSup">3</span> it has not been possible to diminish the incidence or mortality of this disease since the sensitivity of conventional cytology is low &#40;50-60&#37;&#41;&#46;<span class="elsevierStyleSup">2</span></p> <p class="elsevierStylePara">In order to increase the sensitivity of screening methods&#44; new ancillary techniques have been implemented at a national level in Mexico&#46; Among these are liquid-based cytology and molecular biology tests&#46;</p> <p class="elsevierStylePara">Hybrid capture test &#40;HC2&#41;&#44; which detects 13 of the most frequent genotypes of the high-risk HPV virus&#44; is the molecular biology test accepted by the Federal Drug Administration &#40;FDA&#41; since the year 2003&#46;<span class="elsevierStyleSup">5&#44;6</span> This study has the following indications&#58; a&#41; patients with a cytological diagnosis of atypical squamous cells &#40;ASC&#41;&#59; b&#41; post-treatment follow-up&#59; and c&#41; as a support of cytological cervical screening in women over 30 years of age&#46;<span class="elsevierStyleSup">2</span> </p> <p class="elsevierStylePara">Several studies have also included polymerase chain reaction &#40;PCR&#41; HPV diagnosis as a reinforcement of HC2 test&#44; due to its high sensitivity&#46;<span class="elsevierStyleSup">2&#44;5&#44;7&#44;8</span></p> <p class="elsevierStylePara">The first indication to perform these tests is a cytological interpretation of ASC&#46; This term was introduced by the Bethesda System of Reporting Cervical Cytology in 1988<span class="elsevierStyleSup">9</span> and modified in 2001&#46;10 </p> <p class="elsevierStylePara">In the U&#46;S&#46;A&#46; this diagnosis is reported in nearly two million women annually&#44;<span class="elsevierStyleSup">5</span> and in the National Cancer Institute in Mexico City&#44; in 1-1&#46;5&#37; of reviewed cytologies&#46;<span class="elsevierStyleSup">11</span> The term ASC refers to borderline lesions that surpass the reactive processes but that do not bring together the requirements for diagnosis of a low-grade intraepithelial lesion that requires strict follow-up&#46; </p> <p class="elsevierStylePara"> Cytomorphological criteria for diagnosing ASC are well established&#44; but are subjective&#46;<span class="elsevierStyleSup">10 </span>Therefore&#44; an overdiagnosis of this entity predominates&#44; with the consequent increase in colposcopy studies&#44; and unnecessary treatments with excessive costs&#46;<span class="elsevierStyleSup">12 </span></p> <p class="elsevierStylePara">The objective of the present work was to evaluate whether cytomorphological criteria used in diagnosis of ASC at the National Cancer Institute of Mexico correlate with the presence of high-risk HPV types&#44; justifying thus the performance of molecular biology tests &#40;HC2 and&#47;or PCR&#41; for follow-up of only positive cases&#46; </p> <p class="elsevierStylePara"><span class="elsevierStyleBold">¿METHODS</span></p> <p class="elsevierStylePara">This study included 100 patients selected with a cytological report of ASC&#46; This diagnosis was performed with conventional cytology applied to patients assisting to theGynecological Department of the National Cancer Institute of Mexico from 2007-2008&#46; Patients signed a letter of informed consent&#46; Exclusion criteria included the following&#58; refusal to participate in the study and insufficient sample amount for molecular diagnosis&#46; A prospective&#44; observational&#44; and transversal study was conducted&#46; We considered the following as risk factors&#58; age&#59; number of sexual partners&#44; and age of first sexual intercourse &#40;FSI&#41;&#46;</p> <p class="elsevierStylePara">Patients diagnosed with ASC were required for a new sample for molecular biology studies&#58; HC2&#44; and PCR&#46;</p> <p class="elsevierStylePara">Initial conventional cytology was carried out with an Ayre spatula and cervical brush from exocervix and transformation zone&#46; The sample was fixed with 96&#37; alcohol and stained according to the Papanicolaou technique&#46; For HC2 and PCR tests&#44; samples were taken with a cervical brush and fixed in STM Digene Liquid and 1 ml Lysis buffer &#40;Tris-HCl 10 mmol&#47;L pH 8&#46;0&#44; EDTA 0&#46;1 mol&#47;L pH 8-0&#44; SDS 0&#46;5&#37;&#44; Proteinase K 200 &#956;g&#47;mL&#44; RNase A 20 &#956;g&#47;mL&#41;&#44; respectively&#46;</p> <p class="elsevierStylePara">Initial ASC diagnosis was made during routine laboratory work with conventional cytology samples stained with the Papanicolaou technique&#44; screened by a senior cytotechnologist&#44; and reviewed by an experienced cytopathologist&#46; </p> <p class="elsevierStylePara">The cytological diagnostic criteria were uniform according to the Bethesda System of Reporting Cervical Cytology 2001<span class="elsevierStyleSup">10</span> guidelines&#44; which state that an ASC should show an increase in nuclear size of 2&#46;5-3 times related to the nucleus of normal intermediate cells&#44; slight irregularity in the nuclear contour and a slight change in the chromatin pattern &#40;<span class="elsevierStyleBold">Figures 1a&#44; b</span>&#41;&#46;</p> <p class="elsevierStylePara"> <img src="305v09n05-13187138fig1.jpg" alt="Figure 1&#46; ASC diagnosis&#58; a&#41; Papanicolaou staining&#58; altered intermediate cell with nuclear growth 2&#46;5-3 times the size of the nucleus of a normal intermediate cell &#40;400x&#41;&#46; b&#41; Papanicolaou staining&#58; altered deep cell&#44; with slight growth and nuclear irregularity&#44; slight hyperchromatism &#40;400x&#41;&#46;"/></p> <p class="elsevierStylePara"><span class="elsevierStyleBold"> Figure 1&#46; </span>ASC diagnosis&#58; a&#41; Papanicolaou staining&#58; altered intermediate cell with nuclear growth 2&#46;5-3 times the size of the nucleus of a normal intermediate cell &#40;400x&#41;&#46; b&#41; Papanicolaou staining&#58; altered deep cell&#44; with slight growth and nuclear irregularity&#44; slight hyperchromatism &#40;400x&#41;&#46;</p> <p class="elsevierStylePara">HPV DNA detection by the HC2 method &#40;Digene Co&#46;&#44; Gaithersburg&#44; MD&#44; USA&#41; comprises a single stranded DNA hybridized with RNA probes directed to high- and intermediate-risk viruses &#40;16&#44; 18&#44; 31&#44; 33&#44; 35&#44; 39&#44; 45&#44; 51&#44; 52&#44; 56&#44; 58&#44; 59&#44; and 68&#41;&#44; and a chemioluminiscent detection of the signal&#46; PCR is an enzymatic amplification of DNA that allows the detection of very low levels of DNA copies through an exponential amplification of a selected region&#46; For HPV detection samples were digested with 1 mL of lysis buffer at 55 &#186;C for 3 h&#46; DNA was extracted with phenol&#47;chloroform precipitations as described by Sambrook <span class="elsevierStyleItalic">et al&#46;</span><span class="elsevierStyleSup">13</span> As extended DNA quality control DNA was amplified for &#223;-globin gene &#40;PCO4&#47; GH2O&#41; under conditions described by Resnick <span class="elsevierStyleItalic">et al&#46;</span><span class="elsevierStyleSup">14</span> Samples were later submitted to HPV amplification with three sets of the following universal primers recognizing distinct size fragments of L1 gene&#58; L1C1&#47;L1C2&#44; MY09&#47; MY11&#44; and GP5&#47;GP6&#46;<span class="elsevierStyleSup">15&#44;16</span> DNA extracted from CaSkiand Hela-HPV positive cell lines were used as positive controls&#46; Each amplification reaction was carried out in a 20-&#956;l volume containing 2 mM dNTPs&#44; 0&#46;5 U de Amplitaq Gold DNA polymerase&#44; 1&#46;5-3&#46;0 mM of MgCl<span class="elsevierStyleInf">2</span>&#44; buffer 10X&#44; 10 pM of each oligonucleotide&#44; and water&#46; Temperatures of denaturation&#44; alignment&#44; and extension depended on the oligonucleotide set employed&#46; HPV PCR products were electrophoresed in a 1&#46;2&#37;agarose gel and visualized by ethidium bromide staining&#46;HPV typing was carried out by direct sequencing ofPCR products by means of the BigDye<span class="elsevierStyleSup">TM</span> Terminatorv3&#46;1 Cycle Sequencing Kit &#40;Applied Biosystems&#41;&#46; Theresulting sequences were analyzed in BLAST data bankfor comparison with known HPV sequences&#46;</p> <p class="elsevierStylePara"><span class="elsevierStyleItalic">Kappa</span> agreement between the two tests &#40;HC2&#47; PCR&#41; was calculated&#46;<span class="elsevierStyleSup">17</span> Cytological diagnosis data &#40;ASC&#41; and positivity for HC2 and PCR tests were correlated with clinicopathological variables analyzed&#46; Patient follow-up was carried out at least for one year&#46; </p> <p class="elsevierStylePara"><span class="elsevierStyleBold">¿ RESULTS</span></p> <p class="elsevierStylePara">Age of the 100 patients included in this study ranged between 18 to 80 years&#44; with a mean of 43 years and a median of 46 years&#46; Descriptive values of the studied variables according to its relation with presence or absence of HPV&#44; were analyzed&#46; Risk factors for developing squamous intraepithelial lesions &#40;SIL&#41; and&#47;or carcinoma considered in this study were the following&#58; age&#44; number of sexual partners&#44; and age at first sexual intercourse&#46; Forty one patients &#40;41&#37;&#41; declared one sexual partner&#46; First sexual intercourse was declared in a range between 11-49 years&#44; with an average age of 27 years and a median age of 20 years&#46; Variables were analyzed in order to find any association with HPV positivity&#46; Neither of the variables showed any significant association&#44; including declared number of sexual partners&#46; </p> <p class="elsevierStylePara"><span class="elsevierStyleBold">Table 1</span> shows a comparative analysis of HC2 and PCR for HPV DNA detection&#46; A total of 40&#37; of the patients were HPV positive by any assay&#46; Particularly&#44; the PCR assay detected 35 HPV positive cases&#44; while HC2 test detected 24 positive cases&#46; 19&#37; of the samples resulted HPV positive for both tests&#44; as 60&#37; were negative for both test&#46; Meanwhile&#44; 21&#37; had a discordant result &#40;16 &#37; were only positive for PCR amplification&#59; and 5&#37; were only positive by HC2&#41;&#46; Kappa value was 0&#46;502 &#40;IC 95&#37; 0&#46;313-0&#46;691&#41; with 50&#46;2&#37; of agreement between the two methods&#44; which was greater than that expected by chance&#59; hence the interpretation was a moderate agreement&#44; and the significance level was <span class="elsevierStyleItalic">p </span> <0 0001 with 95 confidence intervals of 0 313-0 691</0></p> <p class="elsevierStylePara"> <img src="305v09n05-13187138fig2.jpg" alt="Table 1&#46; Comparison of HPV detection by HC2 assay and PCR in patients with ASC diagnosis&#46; No&#46; of samples with the following results"/></p> <p class="elsevierStylePara">Viral genotypes were identified by direct sequencing of PCR products&#46; Correlations with HC2 findings are shown in <span class="elsevierStyleBold">Table 2</span>&#46; Cases with viral genotypes 11&#44; 62&#44; 81&#44; and 102 were found negative in CH2 test&#44; which is explained by the fact that these viral types are not included among the 13 genotypes detected by this method&#46; Nevertheless&#44; two cases positive to HPV53&#44; one to HPV66&#44; and one to HPV82&#44; tested positive also for CH2 even though these viral types are neither included in the geno-types detected by HC2 test&#46; </p> <p class="elsevierStylePara"> <img src="305v09n05-13187138fig3.jpg" alt="Table 2&#46; Identification of viral genotypes by PCR test and correlation with HC2 in patients with a cytological diagnosis of ASC&#46;"/></p> <p class="elsevierStylePara">Clinical or histopathological data of patients with one-year follow-up is shown in <span class="elsevierStyleBold">Table 3</span>&#46; Most of the patients continued asymptomatic &#40;90&#47;100&#41;&#46; Seven of them presented aceto-positive colposcopical lesions&#59; ten&#44; atrophic epithelia&#59; and 4 patients presented nuclear enlargement due to chemo &#40;QT&#41;- or radiotherapy &#40;Rt&#41;&#46; The most important observation was that obtained for 10 cases that developed SIL &#40;squamous intraepithelial lesion&#41; or cervical carcinoma in one-year follow-up&#46; In <span class="elsevierStyleBold">Table 4</span> are disclosed the histopathological diagnosis of these ten cases and their correlation with HPV results&#46; Seven cases resulted positive for high-risk HPV types&#44; as classified by de Villiers <span class="elsevierStyleItalic">et al</span>&#44;<span class="elsevierStyleSup">18</span> &#40;HPV types 53&#44; 16&#44; 52&#44; 51&#44; 18&#44; and 58&#41;&#44; from which only four were detected by HC2&#46; However&#44; three precursor lesions&#58; one cervical intraepithelial lesion &#40;CIN-1&#41;&#44; one vaginal intraepithelial lesion &#40;VIEL-1&#41;&#59; and one CIN-2 resulted HPV negative by both tests&#46; </p> <p class="elsevierStylePara"> <img src="305v09n05-13187138fig4.jpg" alt="Table 3&#46; Histopathological diagnosis and follow-up of patients with an initial diagnosis of ASC&#46; "/></p> <p class="elsevierStylePara"> <img src="305v09n05-13187138fig5.jpg" alt="Table 4&#46; Identification of viral genotypes in ten patients with an initial diagnosis of Atypical squamous cells &#40;ASC&#41; and histopathological diagnosis of CIN and&#47;or carcinoma&#46;"/></p> <p class="elsevierStylePara"><span class="elsevierStyleBold">¿ DISCUSSION</span> </p> <p class="elsevierStylePara">In cervical cytology screening&#44; atypical squamous cells of undetermined significance &#40;ASC-US&#41; is an equivocal category assigned to specimens with morphologic changes suggestive of cervical intraepithelial neoplasia but which may also represent non-neoplastic conditions of various causes&#46;<span class="elsevierStyleSup">5&#44;9&#44;10</span> Therefore&#44; it is a borderline lesion that requires strict follow-up&#46; Cytological diagnostic parameters for this entity are subjective and if interpretation is incorrect&#44; it can give rise to an over or under diagnosis with the consequent expensive follow-up and patient miss-treatment&#46; In the USA&#44; two million women are diagnosed with ASC annually&#46;<span class="elsevierStyleSup">5</span> The cost of follow-up and overtreatment of these patients is very high&#46; Kulansingam and colleagues<span class="elsevierStyleSup">12</span> report that performing a colposcopy in every women with a cytological diagnosis of ASC is more expensive than performing it exclusively in women with cytological diagnosis of ASC and HPVDNA positive test &#40;&#36;20 370 <span class="elsevierStyleItalic">vs&#46;</span> &#36;3117dollars &#40;USD&#41; &#47; HSIL diagnosed case&#41;&#46;</p> <p class="elsevierStylePara">Since quality assurance for the interpretation of ASC is important&#44; international guidelines recommend that ASC diagnosis should correspond to no more than 5&#37; of the laboratory cytological material&#44; or that the ASC diagnosed cases should be no more than 2-3 times the number of SIL cases&#46;<span class="elsevierStyleSup">10 </span>In such sense&#44; is relevant to mention that at the cytopathology laboratory of the National Cancer Institute of Mexico&#44; one to 1&#46;5&#37; of the studies &#40;with a mean of 15 cases per month&#41; are reported as ASC&#46;<span class="elsevierStyleSup">11</span> Nevertheless&#44; it is clear that the ASC&#47;SIL ratio as a measure of quality assurance may be an imperfect tool due to the subjective parameters used in the cytological diagnosis of ASC&#46; Therefore&#44; as other authors have proposed&#44;<span class="elsevierStyleSup">12&#44;19</span> HPV DNA testing may be helpful to improve follow-up triage&#46; Different authors cite that 34 to 50&#37; of ASC diagnosed cases will be positive for high-risk HPV DNA&#46;<span class="elsevierStyleSup">19&#44;20</span></p> <p class="elsevierStylePara">L&#246;rincz <span class="elsevierStyleItalic">et al</span><span class="elsevierStyleSup">5</span> mention the benefits of DNA HPV tests&#44; since HC2 tested positive in 100&#37; of HGSIL&#44; compared with 84&#37; of HGSIL detection by means of liquid-based cytology tests and 58&#37; of conventional cytology tests&#46; More recently&#44; as reported in the ASCUS&#47;Low-grade intraepithelial lesions study &#40;ALTS&#41;&#44;<span class="elsevierStyleSup">19</span> HC2 sensitivity was 96&#46;3&#37; compared with 85&#46;3&#37; for liquid-based cytology&#46; </p> <p class="elsevierStylePara">Zahn <span class="elsevierStyleItalic">et al</span><span class="elsevierStyleSup">6</span> consider that the combination of cervical cytology and DNA HPV tests is more sensitive for detecting HGSIL than any of the methods separately&#46; These tests may reduce the diagnosis of invasive carcinomas in 90-92&#37;&#44; compared with 89&#37; of conventional cytology&#44; and may increase the negative predictive value up to 99-100&#37;&#44;<span class="elsevierStyleSup">2 </span>which would justify the extension of the screening interval to approximately five years&#46; </p> <p class="elsevierStylePara">It is important to be aware that HPV DNA results can differ depending on the techniques used&#46; In this study we considered necessary to analyze if the morphological changes found in ASC diagnosed cases were associated to an HPV DNA positive test&#46; We were also interested in comparing both tests&#44; HC2 and PCR&#44; for HPV detection in those samples&#46;</p> <p class="elsevierStylePara">Sixty four percent of cases in the Guo series<span class="elsevierStyleSup">8</span> and 40&#37; in our study were positive for one or both tests performed &#40;HC2 and PCR&#41;&#46; Meanwhile&#44; 60&#37; of our cases resulted HPV DNA negative by the two methods employed&#46; When comparing results obtained by both tests&#44; we found a 21&#37; of disagreement between HC2 and PCR tests&#46; These data are similar to that shown by Ca&#241;adas <span class="elsevierStyleItalic">et al&#44;</span><span class="elsevierStyleSup">7 </span>who also compare both tests obtaining a 16&#37; of discordant results&#46;</p> <p class="elsevierStylePara">According to Meijer et al&#44;<span class="elsevierStyleSup">4</span> patients who test negative for HPV DNA have a minimum risk of developing SIL and&#47;or carcinoma &#40;40-50&#37; lesser risk in 5 years&#41;&#44; suggesting the HC2 performance to conduct follow-up studies exclusively in patients positive for high-risk viral genotypes&#46;</p> <p class="elsevierStylePara">We found that HC2 technique detects a less number of positive cases &#40;24 HPV DNA positive women&#41; than those detected with PCR &#40;35 HPV-positive women&#41;&#44; as reported by Ca&#241;adas <span class="elsevierStyleItalic">et al</span>&#46;<span class="elsevierStyleSup">7</span> This discrepancy can be attributed to a higher sensitivity of the PCR method&#44; which can detect a very low number of viral copies&#46; However&#44; according to several authors&#44; a very low number of copies may have no risk of progression&#46;<span class="elsevierStyleSup">4</span></p> <p class="elsevierStylePara">The five PCR- and HC2&#43; cases can be explained by cross-reactions with other genotypes&#44; generally of low risk&#44; which are not efficiently detected by the PCR oligonucleotides&#46; Otherwise&#44; failures in PCR amplifications due to deletions or sequence intra-type variations can also affect the PCR result&#44; affording a false-negative&#46;<span class="elsevierStyleSup">7</span></p> <p class="elsevierStylePara">Is worth to mention that HPV-16 was the most prevalent genotype found in our study &#40;20&#46;6&#37; of the HPV DNA positive cases&#41;&#44; followed by HPV-51 &#40;11&#46;7&#37;&#41;&#44; and the third place with similar proportions were for HPV-18&#44; -31&#44; -53&#44; and 58&#46; Uncommon types as HPV-102&#44; -82 and -81&#44; were also found&#46;</p> <p class="elsevierStylePara">The 60&#37; of HPV DNA negative may be over diagnosed ASC cases&#44; as suggested by Meijer&#46;<span class="elsevierStyleSup">4</span> Nevertheless&#44; three precursor lesions detected at the one year follow-up&#44; resulted negative for HPV by both tests&#46; Two of the latter cases corresponded to low-grade SIL &#40;CIN-1 and VIEL-1&#41;&#44; which may have a low risk of progression&#46;<span class="elsevierStyleSup">21</span> However&#44; the third case was a high-grade SIL &#40;CIN-2&#41;&#44; which may mean a false negative of both HPV detection methods&#46; When trying to explain the possible causes of ASC over diagnosis&#44; we found that 10 women were in the fifth decade of life&#44; with atrophic epithelia&#46; These atrophic morphological changes may be miss-interpreted as ASC because cervical atrophy is frequently accompanied by exaggerated nuclear growths&#46; Four percent of patients had been previously treated with radiotherapy &#40;Rt&#41; and&#47;or chemotherapy &#40;Qt&#41;&#44; which also have been associated with nuclear growth&#46; However&#44; the majority of miss-diagnosed cases &#40;69 patients&#41; may correspond to borderline inflammatory lesions that possibly may need no follow-up&#46;</p> <p class="elsevierStylePara">Follow-up of HPV DNA positive patients is necessary&#46; Different authors report that during 2 years&#44; 60&#37; of patients become HPV negative during this period and have no risk of developing SIL and&#47;or carcinoma&#46; Whereas according to different series&#44; 10-36&#37; of patients with a cytological diagnosis of ASC and positive for high-risk virus develop high grade SIL&#46;<span class="elsevierStyleSup">14&#44;16</span></p> <p class="elsevierStylePara">In conclusion&#44; the percentage of diagnosis of ASC at the Department of Cytopathology at the National Cancer Institute of Mexico remains within the parameters accepted by the international literature&#46;<span class="elsevierStyleSup">9</span> Nevertheless&#44; only 40&#37; of the cases included in this study were positive to HPV DNA&#44; possibly meaning an over diagnosis of ASC in the majority of HPV negative cases&#46; Seven of ten cases that in a one-year follow-up progressed to SIL or cervical cancer&#44; were positive to high-risk HPV types&#46; These results justify the performance of molecular biology tests&#44; preferably both HC2 and PCR&#44; in ASC diagnosed patients&#44; to strictly follow-up those with HPV DNA positive results&#46; </p> <p class="elsevierStylePara"><span class="elsevierStyleBold">¿ ACKNOWLEDGEMENTS</span></p> <p class="elsevierStylePara">This work was partially supported by CONACyT grant 69875&#46; We thank Dr&#46; Sergio Ponce-de-Leon for statistical assistance&#46; </p> <hr/> <p class="elsevierStylePara"> <span class="elsevierStyleItalic">Correspondence&#58;</span> Dra&#46; Rita Sotelo Regil Hallmann&#46;<br/> Av&#46; San Fernando N&#176; 22&#46; Col&#46; Secci&#243;n XVI&#44; Tlalpan 14080 Mexico&#44; D&#46;F&#46; Mexico&#46;<br/> Telephone&#47;fax&#58; 5628 0468&#46;<br/> <span class="elsevierStyleItalic">E-mail&#58;</span> <a href="mailto&#58;rsotelo24&#64;hotmail&#46;com" class="elsevierStyleCrossRefs">rsotelo24&#64;hotmail&#46;com</a></p> "
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        "resumen" => "Objective&#58; To evaluate whether the cytomorphological criteria used in the diagnosis of ASC at the National Cancer Institute in Mexico City correlate with HPV DNA positive tests&#46; Methods&#58; Cervical samples from 100 patients with a previous diagnosis of ASC were processed for molecular biology studies by means of HC2 and PCR&#46; Kappa agreement was calculated between the two diagnostic methods&#46; Results&#58; Sixty percent of patients were negative for both tests&#44; 19&#37; were positive for both tests&#44; and 21&#37; exhibited discrepancies&#46; Kappa value was 0&#46;502 &#40;50&#46;2&#37;&#41; of agreement between the two methods&#46; In one-year follow-up studies&#44; ten patients showed SIL or carcinoma&#44; being 7 of them positive to HR-HPV&#46; Conclusions&#58; ASC is over diagnosed by cytological criteria&#46; Even though a small percentage of cases may escape from detection&#44; molecular biology HPV tests in all patients with a cytological report of ASC may be helpful to detect progressive lesions&#46;"
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        "resumen" => "Objetivo&#58; Evaluar si los criterios citomorfol&#243;gicos utilizados en el diagn&#243;stico citol&#243;gico de ASC en el Instituto Nacional de Cancerolog&#237;a&#44; M&#233;xico&#44; correlacionan con pruebas positivas para la detecci&#243;n de DNA de virus del papiloma humano&#46; M&#233;todos&#58; Se seleccionaron 100 muestras de pacientes con diagn&#243;stico citol&#243;gico de ASC las cuales se procesaron para estudios biomoleculares &#40;CH2 y PCR&#41;&#46; Se calcul&#243; la concordancia Kappa entre los dos m&#233;todos diagn&#243;sticos&#46; Resultados&#58; Fueron negativas para ambas pruebas 60&#37; de las pacientes&#59; fueron positivas para ambas pruebas 19&#37; y mostraron discrepancia 21&#37;&#46; El valor Kappa fue 0&#46;502 &#40;50&#46;2&#37;&#41; de concordancia entre los dos m&#233;todos diagn&#243;sticos&#46; En un a&#241;o de seguimiento&#44; 10 pacientes desarrollaron LIE o carcinoma&#44; siete de ellas fueron positivas a virus de alto riesgo&#46; Conclusiones&#58; La entidad ASC est&#225; sobre diagnosticada con los criterios citol&#243;gicos&#46; Aunque un porcentaje peque&#241;o de los casos puede escapar la detecci&#243;n&#44; la biolog&#237;a molecular con pruebas para detectar VPH en pacientes con diagn&#243;stico de ASC es &#250;til en la detecci&#243;n de lesiones progresivas&#46;"
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ISSN: 16659201
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