Anatomic Pathology / UNNECESSARY TREATMENTS IN CERVICAL SCREENING

Size: px
Start display at page:

Download "Anatomic Pathology / UNNECESSARY TREATMENTS IN CERVICAL SCREENING"

Transcription

1 Anatomic Pathology / UNNECESSARY TREATMENTS IN CERVICAL SCREENING The Risk of False-Positive Histology According to the Reason for Colposcopy Referral in Cervical Cancer Screening A Blind Revision of All Histologic Lesions Found in the NTCC Trial Paolo Dalla Palma, MD, 1 Paolo Giorgi Rossi, PhD, 2 Guido Collina, MD, 3 Anna Maria Buccoliero, MD, 4 Bruno Ghiringhello, MD, 5 Maurizio Lestani, MD, 6 Gianlibero Onnis, MD, 7 Daniela Aldovini, MD, 1 Giuseppe Galanti, MD, 8 GianPiero Casadei, MD, 9 Mirella Aldi, MD, 10 Vincenzo Gomes, MD, 11 Pamela Giubilato, MSc, 12 Guglielmo Ronco, MD, 12 and the NTCC Pathology Group* Key Words: Cervical neoplasia; Histology; Colposcopy biopsy; Sensitivity; Specificity; Positive predictive value Abstract All cervical intraepithelial neoplasia (CIN) diagnoses identified during the New Technologies for Cervical Cancer trial (ISRCTN ) were blindly reviewed by 2 pathologists. Original diagnoses based on colposcopy-guided biopsies were compared with those made by the reviewers who had access to all clinical histologic samples (including postsurgical). Cases downgraded from CIN 2+ by the reviewers were considered indicative of unnecessary treatments. The analyses are presented according to the molecular (high-risk human papillomavirus [HPV]) and/or cytologic diagnosis used to refer the women for colposcopy. We reviewed 812 CIN 1 and 364 CIN 2+ diagnoses. The specificity of colposcopy-guided biopsy was 98% and the sensitivity, 84%. The probability of unnecessary treatment was 27% for women with atypical squamous cells of undetermined significance cytologic findings and 8% for women with low-grade squamous intraepithelial lesion or worse, 10% for HPV+ and positive cytologic findings, and 16% for HPV+ alone. The positive predictive value of the first-level screening test was inversely associated with probability of a histologic false-positive result (P =.015). In screening, a low positive predictive value of the colposcopy-referring test may result in unnecessary treatments. When deciding which test to use for screening, specificity must be taken into account because tests with low specificity applied to a healthy population with a very low prevalence of disease will result in a high proportion of false-positive test results (low positive predictive value [PPV]). Women with positive test results in cervical cancer screening are usually referred for colposcopy, and treatment is based on the biopsy results. Women with cervical intraepithelial neoplasia (CIN) grade 2 (CIN 2) or higher usually are treated. A false-positive histologic diagnosis very likely leads to unnecessary treatment. Errors in cervical histologic findings have been documented, 1,2 and CIN diagnoses are not entirely reproducible A multicenter, randomized, controlled trial began in March 2002 to evaluate the effectiveness of new technologies (Hybrid Capture test [Digene, Gaithersburg, MD] for highrisk human papillomavirus [HPV] alone and with liquid-based cytology vs conventional Papanicolaou [Pap] smear) in a population-based cervical cancer screening program (New Technologies for Cervical Cancer screening [NTCC]). 12,13 The study involved 9 organized screening programs in 6 regions of Italy, and about 95,000 women were enrolled. A histopathologic diagnosis of CIN 2 or higher was considered as the study end point. To increase the validity of trial results and avoid ascertainment bias (the study was not masked), we blindly reviewed all histologic diagnoses of CIN 1, 2, and 3. The unusual situation of having all histologic results obtained during the diagnostic process (not blinded to the cytologic and HPV results) and the blinded revision of all CIN 1, CIN 2, and higher gave us the opportunity to estimate the probability of histologic false-positive results and, therefore, of unnecessary future treatments, given the cytologic and HPV results that led to colposcopy. Downloaded from Am J Clin Pathol 2008;129:

2 Dalla Palma et al / UNNECESSARY TREATMENTS IN CERVICAL SCREENING Materials and Methods The NTCC study enrolled about 95,000 women who were screened according to various schedules. Protocols have been detailed elsewhere. 12,13 Briefly, in the first phase (about 45,000 women), women in the control arm had a conventional Pap smear, and women in the experimental arm had a liquid-based sample taken and tested for cytologic features and HPV. Women older than 35 years with atypical squamous cells of undetermined significance (ASCUS)+ or HPV+ results were directly referred for colposcopy, whereas women younger than 35 years with ASCUS+ results were directly referred for colposcopy independent of the HPV result and recalled after 1 year for cytologic examination and/or HPV control if the HPV result was positive and the cytologic findings negative. These latter results are not included in the present analysis. In the second phase (50,000 women), women in the control arm were still tested with conventional cytologic examination, whereas women in the experimental arm received only the HPV test and positive results were referred directly for colposcopy, independent of age. Colposcopic and histologic diagnoses were made without masking cytologic and/or HPV results. Histologic diagnoses were given by 10 pathology services. The histologic samples diagnosed as CIN 2 or 3 or CIN 1 were blindly reviewed. We retrieved all available histologic samples taken within 1 year from referral for colposcopy: punch biopsies, in some cases from more than 1 colposcopy, and the surgical specimens when an ablative treatment was performed. Each case was randomly assigned to 1 or 2 pathologists for review. Only H&E-stained slides were used. The only data available to reviewers were patient age and date the sample was obtained. Each reviewer was asked to formulate a single diagnosis for each patient, corresponding to the worst pathologic finding among all the patient s tests, according to the following 5 categories: (1) negative or inflammation, (2) CIN 1 encompassing HPV condyloma, (3) CIN 2, (4) CIN 3, or (5) carcinoma (encompassing squamous carcinoma and adenocarcinoma). In the second phase, 2 independent pathologists randomly selected from a pool of 9 (1 per center, excluding the center that made the first diagnosis) reviewed all cases. In phase 1, all diagnoses of CIN 2 or 3 and 42% of CIN 1 diagnoses were reviewed. During phase 1 the remaining CIN 1 cases were reviewed by only 1 pathologist who was randomly selected from the 3 most expert. This was done to reduce the workload and seems not to have influenced the results. Indeed, the proportion of CIN 1 upgraded to CIN 2 or worse did not differ by method (P =.98). The diagnoses provided by the reviewers were compared with the diagnoses originally given by the screening center. The following concordance-categories were defined: (1) All diagnoses were identical (perfect agreement). (2) The diagnoses differed, but all were CIN 1 or less severe. (3) The diagnoses differed, and all were CIN 2 or more severe. (4) One diagnosis was CIN 2 or worse, whereas the others were CIN 1 or better, or vice versa (major disagreement, to review further). (5) At least one diagnosis was carcinoma (to review further). Categories 4 and 5 were reviewed and discussed by all pathologists involved, using a multiheaded microscope. Again, all available material was examined, and only 1 diagnosis per woman, corresponding to the worst pathologic finding, was formulated. When possible, the diagnosis was agreed on by consensus. Otherwise the majority diagnosis was chosen. Statistical Analysis We considered original diagnoses of CIN 2 or worse given by the pathology clinic after colposcopy-guided histology but before treatment. We computed the proportion that were not confirmed by the reviewers diagnosis as an estimate of the probability of unneeded treatment. Indeed, the decision to refer for treatment is based on colposcopy-guided histologic findings. We used as the gold standard the reviewers final diagnosis, based on all available material as described earlier, because we considered it to represent the best available assessment of whether a CIN 2 or worse lesion was present. The estimated proportion corresponds to 1 (the PPV of the pretreatment histologic diagnosis). We also computed the sensitivity and specificity of the original pretreatment diagnosis vs the gold standard. In that analysis, biopsy specimens showing no CIN, which were not reviewed, were considered true-negatives. We calculated 95% confidence intervals (CIs) for all proportions assuming a binomial distribution. All of these parameters were estimated separately according to the cytologic and HPV results that preceded colposcopy to evaluate the association between the PPV of the diagnostic category and the probability of a false-positive histologic result. Results There were 52 CIN cases unavailable for review, and 1,128 cases were reviewed: 747 had an initial diagnosis of CIN 1, 349 were CIN 2 or worse, and 20 were CIN not otherwise specified colposcopy-guided biopsy diagnoses. The latter 20 were considered CIN 1 or better in the analysis. We excluded 12 cases from this analysis because the colposcopyguided biopsy diagnosis was unclear or not available. Table 1 shows the distribution of the colposcopy-guided biopsy histologic diagnoses according to the final diagnosis after revision. The sensitivity of the pretreatment original 76 Am J Clin Pathol 2008;129:75-80 Downloaded 76 from

3 Anatomic Pathology / ORIGINAL ARTICLE Table 1 Original Pretreatment Histologic Diagnosis by Diagnosis Based on Pretreatment and Posttreatment Specimens Histologic Diagnosis Original Pretreatment Squamous Histologic Diagnosis Inadequate Normal CIN 1 CIN 2 CIN 3 Carcinoma Total Unavailable CIN NOS CIN CIN CIN Total ,128 CIN, cervical intraepithelial neoplasia; NOS, not otherwise specified. histologic diagnoses for CIN 2 or worse was 82.5%, and specificity was 97.9% (2,383/2,435). The percentage of CIN 1 cases upgraded to CIN 2 or worse after review was 8.1% (ie, the negative predictive value for CIN 2 or worse was about 92%), whereas the percentage of CIN 2 or worse downgraded (the probability of a false-positive diagnosis of CIN 2 or worse) was 14.9% (ie, the PPV was about 85%) Table 2. We observed similar rates of specificity of colposcopyguided biopsy, ranging from 97% to 99%, independent of the reason for the colposcopy referral, ie, ASCUS, low-grade squamous intraepithelial lesion (LSIL)+, HPV+ and negative cytologic results or HPV+ and positive cytologic results Table 3 and Figure 1. Sensitivity ranged between 75% and approximately 90% (except for the HPV group that included only 3 cases that were CIN 2 or worse), and there was no evidence of significant variation between groups. On the other hand, the proportion of false-positive diagnoses of CIN 2 or worse varied according to cytologic and HPV test results (Table 3 and Figure 1). It was higher in the Table 2 Dichotomized Diagnosis, Positive Predictive Value, and Sensitivity * Histologic Diagnosis Original Pretreatment CIN 1 CIN 2 Histologic Diagnosis or Better or Worse Total CIN 1 or better CIN 2 or worse Total ,116 CIN, cervical intraepithelial neoplasia. * Positive predictive value, 85.1%; sensitivity, 83.9%. conventional arm (P =.02) for women with ASCUS cytologic findings (26.7%; 95% CI, 12%-46%) than for women who had LSIL or more severe cytologic results (8.6%; 95% CI, 4%-16%). In the experimental arm, it was higher (P =.003) for HPV but cytologically abnormal (ASCUS+) cases (66.7%; 95% CI, 22%-96%) than for HPV+ cases (10.6%; Table 3 Number of Biopsies and CIN 2 or Worse Diagnoses After Revision, Sensitivity, Specificity, and Probability of Unnecessary Treatment According to the HPV and Cytologic Results Used to Refer Women for Colposcopy No. of No. of Cases No. of CIN 2 or Sensitivity, % Specificity, % Probability of False CIN 2 or HPV/Cytologic Results Cases Worse (95% CI) (95% CI) Worse Diagnosis, % (95% CI) No HPV test Overall (74-88) 97.1 (95-98) 15.0 (8-20) ASCUS (56-90) 97.0 (94-99) 26.7 (12-45) LSIL (84-97) 97.2 (95-99) 8.6 (4-16) HPV+ No test (80-93) 96.9 (95-98) 15.7 (10-23) Overall HPV and cytology (74-89) 97.9 (96-99) 10.6 (5-18) Normal cytology (51-91) 99.0 (97-100) 11.8 (1-36) ASCUS (66-97) 99.0 (94-100) 4.8 (0-24) LSIL (74-93) 95.7 (92-98) 12.1 (5-22) HPV Overall ( ) 98.7 (98-100) 66.7 (22-96) ASCUS ( ) 99.4 (97-100) 50.0 ( ) LSIL ( ) 97.8 (94-100) 80.0 ( ) ASCUS, atypical squamous cells of undetermined significance; CI, confidence interval; CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus; LSIL, low-grade squamous intraepithelial lesion. Downloaded from Am J Clin Pathol 2008;129:

4 Dalla Palma et al / UNNECESSARY TREATMENTS IN CERVICAL SCREENING Cytology Normal ASCUS LSIL+ None None 169 (2 CIN 2) Colposcopic CIN CIN Total (14 CIN 2) 204 Colposcopic CIN CIN Total HPV Positive 163 (1 CIN 2) Colposcopic CIN CIN Total (2 CIN 2) Colposcopic CIN CIN Total (3 CIN 2) Colposcopic CIN CIN Total (15 CIN 2) 371 Colposcopic CIN CIN Total Negative 139 (0 CIN 2) Colposcopic CIN CIN Total (0 CIN 2) Colposcopic CIN CIN Total Figure 1 Flow chart of the women enrolled in the trial according to the results of the first-level screening test (cytology in columns and human papillomavirus [HPV] in rows) and results of histologic review. For the original diagnosis, we considered only the colposcopy-guided biopsy specimen, whereas the review also included the postsurgical histologic findings, when present. ASCUS, atypical squamous cells of undetermined significance; CIN, cervical intraepithelial neoplasia; CIN 1, CIN or better; CIN 2+, CIN 2 or worse; LSIL, low-grade squamous intraepithelial lesion. 95% CI, 5%-18%), without significant variation or trend according to the severity of cytologic findings. Finally, the lesions found in HPV+ women without a Pap test, examined during the second phase of the trial, had a probability of being falsely classified as CIN 2 or worse of 15.7% (95% CI, 10%- 23%). This proportion was not statistically different from that observed overall among women with conventional cytologic diagnoses (P =.4) or among HPV+ women recruited during phase 1 who had simultaneous cytologic examination and HPV testing (P =.2). The highest probability of a false-positive histologic diagnosis of CIN 2 or worse (66.7%) was observed in the group with abnormal cytologic findings (ASCUS or worse) but negative HPV results that also had the lowest PPV among all screening test combinations (0.4%). There was a statistically significant (P =.015) inverse correlation between the PPV of the screening test combination that led to referral and the probability that a histologic diagnosis of CIN 2 or worse from a colposcopy-guided biopsy specimen was false: the r 2 for linear correlation between log(ppv) and log(proportion falsepositive histologic diagnoses) was Discussion The main goal of cervical screening is to identify women with high-grade intraepithelial lesions (CIN 2 or more severe). These women require treatment, whereas women with low-grade lesions (CIN 1 or less severe), which are frequently regressive, should be referred for cytologic or colposcopic control. 14 In our study, 7.4% of women with CIN 1 or less severe pretreatment histologic findings were judged to have CIN 2 or worse. The clinical consequences of this upgrade were minimal 78 Am J Clin Pathol 2008;129:75-80 Downloaded 78 from

5 Anatomic Pathology / ORIGINAL ARTICLE because every woman with a lesion was monitored and the lesion controlled with strict follow-up. On the other hand, about 15% of cases diagnosed as CIN 2 or worse before treatment were downgraded to CIN 1 or less. This proportion changed according to the combination of screening test results that preceded the colposcopy. This phenomenon is the consequence of the fact that sensitivity and specificity were constant in these groups, whereas the prevalence of CIN 2 or worse among women who had a biopsy varied. Because the prevalence of CIN 2 or worse among women with a biopsy is correlated to the prevalence in the entire group, the PPV of histologic diagnoses was correlated with the PPV of the initial screening test combination. This observation has important clinical implications. Histologic diagnoses determine the decision to treat. Therefore, the proportion of cases of CIN 2 or worse downgraded after review can be assumed to represent the probability of a treatment for CIN 2 or worse to be unnecessary. Our data show that this probability can be relevant in some groups of women if they are directly referred for colposcopy, such as women with negative HPV results but abnormal cytologic results, especially ASCUS, which supports the use of HPV for cytologic triage. In general, our results stress the need for initial tests with a high PPV. In screening, a low PPV of the diagnostic tests that directly refer to colposcopy results not only in increased workload and costs for colposcopy units, but also unnecessary treatments. In the study by Hopman and colleagues, 15 20% of lowgrade lesions were upgraded and 26% of high-grade lesions were downgraded after review. In the analysis by Stoler et al, 5 reviewers reclassified 27% of CIN 1 cases to CIN 2 or worse and 24% of CIN 2 or worse cases to CIN 1. Our high negative predictive value is the result of a low prevalence of true CIN 2 or worse in our series. This also led to a relatively low PPV despite high specificity, 98% overall. It must be kept in mind that this last figure estimates the specificity of pretreatment biopsy and, therefore, represents only women who actually had a biopsy. The specificity of the entire second level diagnostic phase, including colposcopy and biopsy, is probably even higher because many women did not have a biopsy and most of them plausibly represent true-negative results for CIN 2 or worse. Because we compared pretreatment diagnosis with reviewed posttreatment diagnoses, false-negatives were indicative not only of errors of local pathologists in interpreting histologic features but also of the different specimens available before and after treatment. The true sensitivity of the whole diagnostic process of colposcopy plus biopsy is even lower because biopsies were not done for all women, and some of the biopsy specimens may not have been taken from the most severe lesion. 16 This results in an overestimate of sensitivity. It has been shown that the portion of CIN 2 or worse missed by colposcopy is not negligible. 5,17 Because biopsy specimens from women with negative diagnoses were not reviewed, we assumed they were all negative for CIN 2 or worse. It is possible that a small number of true cases of CIN 2 or worse are present in this group. This would result in a slight overestimate of sensitivity and a negligible overestimate of specificity. 16 Remarkably, sensitivity and specificity were stable over the different groups, which suggests that knowing why the women were referred for colposcopy had little influence on the interpretation of histologic findings. The similar values of specificity and sensitivity among groups with such a different prevalence of lesions give consistency to our results. Our results also stress the need for quality assurance in cervical histologic diagnosis. Indeed, even if the diagnosis of CIN is believed to be simple and reproducible by most pathologists, in the historic study by Siegler, of 20 cases of carcinoma in situ (actually CIN 3 or high-grade SIL [HSIL]) were missed by a group of 25 pathologists. More recent work found higher agreement: Robertson and collaborators 10 found a Cohen κ (the statistic that measures agreement not due to chance 19 ) of 0.46 for HSIL vs less severe than HSIL; Stoler et al 5 found a κ of 0.69; and Park et al 7 and Parker et al 4 found a κ of about 0.8. Indeed biopsy diagnoses are always considered the gold standard in any study of diagnostic accuracy, but the subjective interpretation of histologic classification is a big obstacle in many interinstitutional studies. 5 In screening, a low PPV of the diagnostic test that directly precedes colposcopy not only has consequences on the colposcopy workload and costs but also leads to unnecessary treatment. This consideration is true independent of the type of first-level test, cytologic examination or HPV testing. From the 1 Pathology Unit, S. Chiara Hospital of Trento, Trento, Italy; 2 Agency for Public Health, Lazio Region, Rome; 3 Pathology Section, University of Bologna, Bologna; 4 Department of Human Pathology and Oncology, University of Firenze, Firenze; 5 Pathology Unit, S. Anna Hospital of Torino, Torino; 6 Department of Pathology, University of Verona, Verona; 7 Section of Cytopathology, Hospital of Padova, Padova; 8 Pathology Unit, Hospital of Imola, Bologna; 9 Pathology Unit, Maggiore Hospital of Bologna, Bologna; 10 Pathology Unit, Hospital of Faenza, Ravenna; 11 Pathology Unit, Belcolle Hospital of Viterbo, Viterbo; and 12 Centro per la Prevenzione Oncologica, Torino. The NTCC trial was financially supported by the European Union (Europe against Cancer contracts SI and SPC ), by the Italian Ministry of Health (Progetto Speciale Valutazione di nuove tecnologie per lo screening del cervicocarcinoma and project ex L 138/2004), Regione Piemonte, Torino, Regione Toscana, Firenze, Regione Veneto, Venezia, Regione Emilia-Romagna, Bologna, Provincia Autonoma di Trento, Agenzia di Sanità Pubblica, Regione Lazio, by the Special Project Oncology, Compagnia di S. Paolo FIRMS, Torino. Address reprint requests to Dr Giorgi Rossi: Agency for Public Health, Lazio Region, via di S. Costanza 53, Rome, Italy. Downloaded from Am J Clin Pathol 2008;129:

6 Dalla Palma et al / UNNECESSARY TREATMENTS IN CERVICAL SCREENING * The following are contributing members of the NTCC Pathology Group: G.L. Taddei, F. Castiglione, and A.M. Buccolero, Unit of Pathology, University, Florence; P. Dalla Palma and D. Aldovini, Unit of Pathology, Ospedale di Trento; B. Ghiringhello and S. Privitera, Unit of Pathology, OIRM, S. Anna, Turin; G. Collina, Unit Section of Anatomic Pathology M. Malpighi, Bellaria Hospital, Bologna University, Bologna; G.P. Casadei and P. Pierotti, Unit of Pathology, Ospedale Maggiore di Bologna, Bologna; M. Aldi and C. Sintoni, Unit of Pathology, Presidio Ospedaliero di Ravenna, Ravenna; G. Galanti, Unit of Pathology, Presidio Ospedaliero di Imola, Bologna; V. Gomes and G. Verrico, U.O.C. di Anatomia e Istologia Patologica, Ospedale Belcolle, Viterbo; M. Lestani, Unit of Pathology, University of Verona; E. Bragantini, Unit of Pathology, Ospedale Borgo Trento, Verona; and G.L. Onnis and D. Minucci, Unit of Pathology, University of Padova. The following are contributors to the article: P. Dalla Palma was the coordinator of the NTCC Pathologist Working Group and designed and conducted the review; P. Dalla Palma, G. Collina, A.M. Buccoliero, B. Ghiringhello, M. Lestani, G. Onnis, D. Aldovini, G. Galanti, G. Casadei, M. Aldi, and V. Gomes reviewed the histologic specimens; G. Ronco was the NTCC project leader and designed the study. P. Giorgi Rossi with P. Dalla Palma and G. Ronco drafted the manuscript. P. Giorgi Rossi, G. Ronco, and P. Giubilato were responsible for data analysis. All authors critically revised the manuscript. All members of the NTCC Pathologist Working Group reviewed the histologic specimens. Acknowledgments: We thank all staff who assisted in running the study, Margaret Becker for editing the text, and the thousands of women who participated in the study. References 1. Joste NE, Crum CP, Cibas ES. Cytologic/histologic correlation for quality control in cervicovaginal cytology; experience with 1,582 paired cases. Am J Clin Pathol. 1995;103: Tritz DM, Weeks JA, Spires SE, et al. Etiologies for noncorrelating cervical cytologies and biopsies. Am J Clin Pathol. 1995;103: Malpica A, Matisic JP, Van Niekirk D, et al. Kappa statistics to measure interrater and intrarater agreement for 1790 cervical biopsy specimens among twelve pathologists: qualitative histopathologic analysis and methodology issues. Gynecol Oncol. 2005;99(3 suppl 1):S38-S Parker MF, Zahn CM, Vogel KM, et al. Discrepancy in the interpretation of cervical histology by gynaecologic pathologists. Obstet Gynecol. 2002;100: Stoler MH, Schiffman M, and the Atypical Squamous Cells of Undetermined Significance Low-grade Squamous Intraepithelial Lesion Triage Study (ALTS) Group. Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study. JAMA. 2001;285: Grenko RT, Abendroth CS, Frauenhoffer EE, et al. Variance in the interpretation of cervical biopsy specimens obtained for atypical squamous cells of undetermined significance. Am J Clin Pathol. 2000;114: Park JJ, Genest DR, Sun D, et al. Atypical immature metaplastic-like proliferations of the cervix: diagnostic reproducibility and viral (HPV) correlates. Hum Pathol. 1999;30: de Vet HC, Knipschild PG, Schouten HJ, et al. Interobserver variation in histopathological grading of cervical dysplasia. J Clin Epidemiol. 1990;43: Ismail SM, Colclough AB, Dinnen JS, et al. Observer variation in histopathological diagnosis and grading of cervical intraepithelial neoplasia. BMJ. 1989;298: Robertson AJ, Anderson JM, Beck JS, et al. Observer variability in histopathological reporting of cervical biopsy specimens. J Clin Pathol. 1989;42: Kalof AN, Cooper K. Our approach to squamous intraepithelial lesions of the uterine cervix. J Clin Pathol. 2007;60: Ronco G, Giorgi-Rossi P, Carozzi F, et al. Human papillomavirus testing and liquid-based cytology in primary screening among younger women: results at recruitment from the NTCC randomised controlled trial. Lancet Oncol. 2006;7: Ronco G, Segnan N, Giorgi Rossi P, et al, for the New Technologies for Cervical Cancer Working Group. Human papillomavirus testing and liquid-based cytology: results at recruitment from the New Technologies for Cervical Cancer randomized controlled trial. J Natl Cancer Inst. 2006;98: Advisory Committee on Cancer Prevention. Recommendation on cancer screening in the European Union. Eur J Cancer. 2000;36: Hopman EH, Kenemans P, Helmerhorst TJ. Positive predictive rate of colposcopic examination of the cervix uteri: an overview of literature. Obstet Gynecol Surv. 1998;53: Adams AL, Eltoum I, Roberson J, et al. Negative colposcopic biopsy after positive human papillomavirus (HPV) DNA testing: false-positive HPV results or false-negative histologic findings? Am J Clin Pathol. 2006;125: Pretorius RG, Peterson P, Azizi F, et al. Subsequent risk and presentation of cervical intraepithelial neoplasia (CIN) 3 or cancer after a colposcopic diagnosis of CIN 1 or less. Am J Obstet Gynecol. 2006;195: Siegler EE. Microdiagnosis of carcinoma in situ of the uterine cervix. a comparative study of pathologists diagnoses. Cancer. 1956;9: Cohen J. A coefficient of agreement for nominal scales. Educ Psychol Measurement. 1960;20: Am J Clin Pathol 2008;129:75-80 Downloaded 80 from

On behalf of the New Technologies for Cervical Cancer Screening Working Group

On behalf of the New Technologies for Cervical Cancer Screening Working Group ARTICLE Results at Recruitment From a Randomized Controlled Trial Comparing Human Papillomavirus Testing Alone With Conventional Cytology as the Primary Cervical Cancer Screening Test Guglielmo Ronco,

More information

Negative Colposcopic Biopsy After Positive Human Papilloma Virus (HPV) DNA Testing False-Positive HPV Results or False-Negative Histologic Findings?

Negative Colposcopic Biopsy After Positive Human Papilloma Virus (HPV) DNA Testing False-Positive HPV Results or False-Negative Histologic Findings? Anatomic Pathology / FALSE-NEGATIVE HISTOLOGIC FINDINGS Negative Colposcopic Biopsy After Positive Human Papilloma Virus (HPV) DNA Testing False-Positive HPV Results or False-Negative Histologic Findings?

More information

Comparative study of human papilloma virus DNA detection and results of histopathological examination of cervical colposcopic biopsy

Comparative study of human papilloma virus DNA detection and results of histopathological examination of cervical colposcopic biopsy Iranian Journal of Reproductive Medicine Vol.5. No.3. pp:121-126, Summer 2007 Comparative study of human papilloma virus DNA detection and results of histopathological examination of cervical colposcopic

More information

Cytology/Biopsy/Leep Gynecologic Correlation: Practical Considerations and Approaches.

Cytology/Biopsy/Leep Gynecologic Correlation: Practical Considerations and Approaches. Cytology/Biopsy/Leep Gynecologic Correlation: Practical Considerations and Approaches. Fadi W. Abdul-Karim MD MEd. Professor of Pathology. Vice chair for education. Robert Tomsich Pathology and Lab Med

More information

Can HPV-16 Genotyping Provide a Benchmark for Cervical Biopsy Specimen Interpretation?

Can HPV-16 Genotyping Provide a Benchmark for Cervical Biopsy Specimen Interpretation? Anatomic Pathology / Monitoring HPV-16 Fractions in CIN Can HPV-16 Genotyping Provide a Benchmark for Cervical Biopsy Specimen Interpretation? Mary T. Galgano, MD, 1 Philip E. Castle, PhD, MPH, 2 Mark

More information

Atypical Glandular Cells of Undetermined Significance Outcome Predictions Based on Human Papillomavirus Testing

Atypical Glandular Cells of Undetermined Significance Outcome Predictions Based on Human Papillomavirus Testing Anatomic Pathology / ATYPICAL GLANDULAR CELLS AND HUMAN PAPILLOMAVIRUS Atypical Glandular Cells of Undetermined Significance Outcome Predictions Based on Human Papillomavirus Testing Jeffrey F. Krane,

More information

Setting The setting was secondary care. The economic study was carried out in Italy.

Setting The setting was secondary care. The economic study was carried out in Italy. Role of p16(ink4a) expression in identifying CIN2 or more severe lesions among HPVpositive patients referred for colposcopy after abnormal cytology Carozzi F, Cecchini S, Confortini M, Becattini V, Cariaggi

More information

Appropriate Use of Cytology and HPV Testing in the New Cervical Cancer Screening Guidelines

Appropriate Use of Cytology and HPV Testing in the New Cervical Cancer Screening Guidelines Appropriate Use of Cytology and HPV Testing in the New Cervical Cancer Screening Guidelines Tim Kremer, MD Ralph Anderson, MD 1 Objectives Describe the natural history of HPV particularly as it relates

More information

These comments are an attempt to summarise the discussions at the manuscript meeting. They are not an exact transcript.

These comments are an attempt to summarise the discussions at the manuscript meeting. They are not an exact transcript. Dear dr. Weber, We would like to thank you for the review of our manuscript entitled Cervical screening with an interval beyond five years requires different rescreen times for HPV-negative and HPVpositive,

More information

Abnormal Cervicovaginal Cytology With Negative Human Papillomavirus Testing

Abnormal Cervicovaginal Cytology With Negative Human Papillomavirus Testing 280 Abnormal Cervicovaginal Cytology With Negative Human Papillomavirus Testing Giovanni Negri, MD Bettina Rigo, BS Fabio Vittadello, ScD Christine Mian, ScD Eduard Egarter-Vigl, MD Department of Pathology,

More information

HPV Testing & Cervical Cancer Screening:

HPV Testing & Cervical Cancer Screening: HPV Testing & Cervical Cancer Screening: Are they linked? By William Chapman, MD, FRCPC Screening for precursor lesions of cervical cancer by the Papanicolaou (Pap) smear has been one of the greatest success

More information

Lessons From Cases of Screened Women Who Developed Cervical Carcinoma

Lessons From Cases of Screened Women Who Developed Cervical Carcinoma Lessons From Cases of Screened Women Who Developed Cervical Carcinoma R. Marshall Austin MD,PhD Magee-Womens Hospital of University of Pittsburgh Medical Center raustin@magee.edu Why Focus Study On Cases

More information

Patients referred to a colposcopy clinic will often have

Patients referred to a colposcopy clinic will often have The Accuracy of the Papanicolaou Smear in the Screening and Diagnostic Settings Marylou Cárdenas-Turanzas, MD, DrPH, 1 Michele Follen, MD, PhD, 2 Graciela M. Nogueras-Gonzalez, MPH, 1 J.L. Benedet, MD,

More information

Outcome of Atypical Squamous Cells in Cervical Cytology: Follow-up Assessment by Loop Electrical Excision Procedure

Outcome of Atypical Squamous Cells in Cervical Cytology: Follow-up Assessment by Loop Electrical Excision Procedure The Korean Journal of Pathology 2012; 46: 359-364 ORIGINAL ARTICLE Outcome of Atypical Squamous Cells in Cervical Cytology: Follow-up Assessment by Loop Electrical Excision Procedure Joon Seon Song Ilseon

More information

Pushing the Boundaries of the Lab Diagnosis in Asia

Pushing the Boundaries of the Lab Diagnosis in Asia Pushing the Boundaries of the Lab Diagnosis in Asia Diana Lim MBBS, FRCPA, FRCPath (UK) Senior Consultant National University Health System and National University of Singapore Department of Pathology

More information

Colposcopy. Attila L Major, MD, PhD

Colposcopy. Attila L Major, MD, PhD Colposcopy Attila L Major, MD, PhD Histology Colposcopy Cytology It has been estimated that annual Pap smear testing reduces a woman s chance of dying of cervical cancer from 4 in 1000 to about 5 in 10,000

More information

HPV Genotyping: A New Dimension in Cervical Cancer Screening Tests

HPV Genotyping: A New Dimension in Cervical Cancer Screening Tests HPV Genotyping: A New Dimension in Cervical Cancer Screening Tests Lee P. Shulman MD The Anna Ross Lapham Professor in Obstetrics and Gynecology and Chief, Division of Clinical Genetics Feinberg School

More information

Original Policy Date

Original Policy Date MP 2.04.03 Cervicography Medical Policy Section Medicine Issue 12:2013 Original Policy Date 12:2013 Last Review Status/Date Reviewed with literature search/12:2013 Return to Medical Policy Index Disclaimer

More information

Acceptable predictive accuracy of histopathology results by colposcopy done by Gynecology residents using Reid index

Acceptable predictive accuracy of histopathology results by colposcopy done by Gynecology residents using Reid index DOI 10.1007/s00404-012-2569-y GYNECOLOGIC ONCOLOGY Acceptable predictive accuracy of histopathology results by colposcopy done by Gynecology residents using Reid index Hadi Shojaei Fariba Yarandi Leila

More information

News. Laboratory NEW GUIDELINES DEMONSTRATE GREATER ROLE FOR HPV TESTING IN CERVICAL CANCER SCREENING TIMOTHY UPHOFF, PHD, DABMG, MLS (ASCP) CM

News. Laboratory NEW GUIDELINES DEMONSTRATE GREATER ROLE FOR HPV TESTING IN CERVICAL CANCER SCREENING TIMOTHY UPHOFF, PHD, DABMG, MLS (ASCP) CM Laboratory News Inside This Issue NEW GUIDELINES DEMONSTRATE GREATER ROLE FOR HPV TESTING IN CERVICAL CANCER SCREENING...1 NEW HPV TEST METHODOLOGY PROVIDES BETTER SPECIFICITY FOR CERVICAL CANCER...4 BEYOND

More information

Comparison of HPV test versus conventional and automation-assisted Pap screening as potential screening tools for preventing cervical cancer

Comparison of HPV test versus conventional and automation-assisted Pap screening as potential screening tools for preventing cervical cancer BJOG: an International Journal of Obstetrics and Gynaecology August 2004, Vol. 111, pp. 842 848 DOI: 1 0. 1111/j.1471-0528.2004.00210.x Comparison of HPV test versus conventional and automation-assisted

More information

Screening for Cervical Cancer. Grand Rounds 1/16/13 Meggan Linck

Screening for Cervical Cancer. Grand Rounds 1/16/13 Meggan Linck Screening for Cervical Cancer Grand Rounds 1/16/13 Meggan Linck Cervical Cancer Worldwide 2 nd most common and 5 th deadliest U.S. 8 th most common 80% occur in developing world Median age at diagnosis

More information

Woo Dae Kang, Ho Sun Choi, Seok Mo Kim

Woo Dae Kang, Ho Sun Choi, Seok Mo Kim Is vaccination with quadrivalent HPV vaccine after Loop Electrosurgical Excision Procedure effective in preventing recurrence in patients with High-grade Cervical Intraepithelial Neoplasia (CIN2-3)? Chonnam

More information

Faculty Pap Smear Guidelines: Family Planning Update 2008 Part Two

Faculty Pap Smear Guidelines: Family Planning Update 2008 Part Two Faculty Pap Smear Guidelines: Family Planning Update 2008 Part Two Seshu P. Sarma, MD, FAAP Emory University Regional Training Center Atlanta, Georgia Produced by the Alabama Department of Public Health

More information

The routine use of ZedScan within one colposcopy service in England. MC Macdonald, R Lyon, JE Palmer, JA Tidy

The routine use of ZedScan within one colposcopy service in England. MC Macdonald, R Lyon, JE Palmer, JA Tidy The routine use of ZedScan within one colposcopy service in England MC Macdonald, R Lyon, JE Palmer, JA Tidy Introduction Colposcopic impression alone has been shown to be subjective with variable rates

More information

P16 et Ki67 Biomarkers: new tool for risk management and low grade intraepithelial lesions (LGSIL): be ready for the future.

P16 et Ki67 Biomarkers: new tool for risk management and low grade intraepithelial lesions (LGSIL): be ready for the future. P16 et Ki67 Biomarkers: new tool for risk management and low grade intraepithelial lesions (LGSIL): be ready for the future. Mark H Stoler, MD University of Virginia Health System, Charlottesville, VA,

More information

The AutoPap Primary Screening System (APSS; Tripath Imaging,

The AutoPap Primary Screening System (APSS; Tripath Imaging, CANCER CYTOPATHOLOGY 129 A Feasibility Study of the Use of the AutoPap Screening System as a Primary Screening and Location-Guided Rescreening Device Massimo Confortini, M.D. 1 Lucia Bonardi, M.D. 1 Paolo

More information

Performance of the Aptima High-Risk Human Papillomavirus mrna Assay in a Referral Population in Comparison with Hybrid Capture 2 and Cytology

Performance of the Aptima High-Risk Human Papillomavirus mrna Assay in a Referral Population in Comparison with Hybrid Capture 2 and Cytology JOURNAL OF CLINICAL MICROBIOLOGY, Mar. 2011, p. 1071 1076 Vol. 49, No. 3 0095-1137/11/$12.00 doi:10.1128/jcm.01674-10 Copyright 2011, American Society for Microbiology. All Rights Reserved. Performance

More information

The Korean Journal of Cytopathology 13(1): 14-20, 2002

The Korean Journal of Cytopathology 13(1): 14-20, 2002 13 1 The Korean Journal of Cytopathology 13(1): 14-20, 2002 : ASCUS 1941 Papanicolaou. The Bethesda System(TBS) 1) 1988, atypical squamous cells of undetermined significance(ascus), low-grade squamous

More information

Biomed Environ Sci, 2015; 28(1): 80-84

Biomed Environ Sci, 2015; 28(1): 80-84 80 Biomed Environ Sci, 2015; 28(1): 80-84 Letter to the Editor Assessing the Effectiveness of a Cervical Cancer Screening Program in a Hospital-based Study* YANG Yi1, LANG Jing He1, WANG You Fang1, CHENG

More information

The devil is in the details

The devil is in the details The cobas KNOW THE RISK For cervical cancer prevention The devil is in the details Leading with the cobas as your primary screening method uncovers disease missed by cytology, and can protect women from

More information

Natural History of HPV Infections 15/06/2015. Squamous cell carcinoma Adenocarcinoma

Natural History of HPV Infections 15/06/2015. Squamous cell carcinoma Adenocarcinoma 14,670 5796 United States/ Canada 17,165 8124 Central America 48,328 21,402 South America 59,929 29,814 Europe 78,896 61,670 Africa 157,759 86,708 Southcentral Asia 61,132 31,314 Eastern Asia 42,538 22,594

More information

Quantitative Optical Spectroscopy of the Uterine Cervix: A cost effective way to detect and manage cervical disease

Quantitative Optical Spectroscopy of the Uterine Cervix: A cost effective way to detect and manage cervical disease Quantitative Optical Spectroscopy of the Uterine Cervix: A cost effective way to detect and manage cervical disease Nahida Chakhtoura, MD, Leo Twiggs, MD, Timothy DeSantis, MD Claudia Werner, MD, William

More information

Over-diagnoses in Cytopathology: Is histology the gold standard?

Over-diagnoses in Cytopathology: Is histology the gold standard? Over-diagnoses in Cytopathology: Is histology the gold standard? Teresa M. Darragh, MD UCSF Departments of Pathology and Obstetrics, Gynecology & Reproductive Sciences Faculty Disclosures: Teresa M. Darragh,

More information

Clinical Guidance: Recommended Best Practices for Delivery of Colposcopy Services in Ontario Best Practice Pathway Summary

Clinical Guidance: Recommended Best Practices for Delivery of Colposcopy Services in Ontario Best Practice Pathway Summary Clinical Guidance: Recommended Best Practices for Delivery of Colposcopy Services in Ontario Best Practice Pathway Summary Glossary of Terms Colposcopy is the examination of the cervix, vagina and, in

More information

SESSION J4. What's Next? Managing Abnormal PAPs in 2014

SESSION J4. What's Next? Managing Abnormal PAPs in 2014 37th Annual Advanced Practice in Primary and Acute Care Conference: October 9-11, 2014 2:45 SESSION J4 What's Next? Managing Abnormal PAPs in 2014 Session Description: Linda Eckert, MD Review current guidelines

More information

Cytology Report Format

Cytology Report Format Squamous Precursor Lesions and Malignancies In Pap Test Dina R. Mody, MD, FCAP Director of Cytology The Methodist Hospital, Houston, TX Professor of Pathology and Laboratory Medicine Weill Medical College

More information

Cytohistologic Discrepancies A Means to Improve Pathology Practice and Patient Outcomes

Cytohistologic Discrepancies A Means to Improve Pathology Practice and Patient Outcomes Anatomic Pathology / CYTOHISTOLOGIC DISCREPANCIES Cytohistologic Discrepancies A Means to Improve Pathology Practice and Patient Outcomes Karen M. Clary, MD, Jan F. Silverman, MD, Yulin Liu, MD, PhD, Charles

More information

Making Sense of Cervical Cancer Screening

Making Sense of Cervical Cancer Screening Making Sense of Cervical Cancer Screening New Guidelines published November 2012 Tammie Koehler DO, FACOG The incidence of cervical cancer in the US has decreased more than 50% in the past 30 years because

More information

BC Cancer Cervix Screening 2015 Program Results. February 2018

BC Cancer Cervix Screening 2015 Program Results. February 2018 BC Cancer Cervix Screening 2015 Program Results BC Cancer Cervix Screening 2015 Program Results 2 Table of Contents BC Cancer Cervix Screening 2015 Program Results... 1 Table of Contents... 2 Program Overview...

More information

Atypical squamous cells. The case for HPV testing

Atypical squamous cells. The case for HPV testing OBG MANAGEMENT FOCUS ON CERVICAL DISEASE BY J. THOMAS COX, MD ASC-US is most often due to transient changes or HPV. HPV-positive ASC-US is 12.5 to 23 times more likely to be associated with CIN 2,3 on

More information

Detecting High-Grade Cervical Disease on ASC-H Cytology. Role of BD ProEx C and Digene Hybrid Capture II HPV DNA Testing

Detecting High-Grade Cervical Disease on ASC-H Cytology. Role of BD ProEx C and Digene Hybrid Capture II HPV DNA Testing Anatomic Pathology / BD ProEx C Use in ASC-H Cy t o l o g y Detecting High-Grade Cervical Disease on ASC-H Cytology Role of BD ProEx C and Digene Hybrid Capture II HPV DNA Testing Momin T. Siddiqui, MD,

More information

PAP SMEAR WITH ATYPICAL SQUAMOUS CELLS OF UNDETERMINED SIGNIFICANCE

PAP SMEAR WITH ATYPICAL SQUAMOUS CELLS OF UNDETERMINED SIGNIFICANCE Arch Iranian Med 2005; 8 (3): 192 196 Original Article PAP SMEAR WITH ATYPICAL SQUAMOUS CELLS OF UNDETERMINED SIGNIFICANCE Fatemeh Ghaemmaghami MD *, Fereshteh Ensani MD**, Nadereh Behtash MD* Ebrahim

More information

Supplementary Appendix

Supplementary Appendix Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Garland SM, Hernandez-Avila M, Wheeler CM, et al. Quadrivalent

More information

Clinical Policy Title: Fluorescence in situ hybridization for cervical cancer screening

Clinical Policy Title: Fluorescence in situ hybridization for cervical cancer screening Clinical Policy Title: Fluorescence in situ hybridization for cervical cancer screening Clinical Policy Number: 01.01.02 Effective Date: April 1, 2015 Initial Review Date: January 21, 2015 Most Recent

More information

Gynecologic Cytology-Histology Correlation Guideline

Gynecologic Cytology-Histology Correlation Guideline Gynecologic Cytology- Correlation Guideline George G. Birdsong, MD and Joe W. Walker, Jr., MS, SCT(ASCP) CM Clinical Practice Committee Dr. Birdsong and Mr. Walker are grateful for extensive input from

More information

Vasile Goldiş Western University of Arad, Faculty of Medicine, Obstetrics- Gynecology Department, Romania b

Vasile Goldiş Western University of Arad, Faculty of Medicine, Obstetrics- Gynecology Department, Romania b Mædica - a Journal of Clinical Medicine ORIGINAL PAPERS Cervical Intraepithelial Neoplasia in the Dr. Salvator Vuia Clinical Obstetrics and Gynecology Hospital - Arad During the 2000-2009 Period Voicu

More information

Human Papillomavirus Testing Using Hybrid Capture II With SurePath Collection

Human Papillomavirus Testing Using Hybrid Capture II With SurePath Collection 468 Human Papillomavirus Testing Using Hybrid Capture II With SurePath Collection Initial Evaluation and Longitudinal Data Provide Clinical Validation for This Method Vincent Ko, MD Rosemary H. Tambouret,

More information

Welcome. THE ROLE OF oncofish cervical ASSESSMENT OF CERVICAL DYSPLASIA. March 26, 2013

Welcome. THE ROLE OF oncofish cervical ASSESSMENT OF CERVICAL DYSPLASIA. March 26, 2013 THE ROLE OF oncofish cervical IN THE ASSESSMENT OF CERVICAL DYSPLASIA The phone lines will open, 15 minutes prior to the start of the webinar. Toll Free: 1-800-867-0864. Entry Code: 83956484. You may download

More information

Evoluzione dello screening cervicale e ruolo del GISCI. Silvia Franceschi, CRO, Aviano NO CONFLICTS OF INTEREST

Evoluzione dello screening cervicale e ruolo del GISCI. Silvia Franceschi, CRO, Aviano NO CONFLICTS OF INTEREST Evoluzione dello screening cervicale e ruolo del GISCI Silvia Franceschi, CRO, Aviano NO CONFLICTS OF INTEREST Lancet. 1984 Oct 6;2(8406):779-82. "Pap" smear and the risk of cervical neoplasia: quantitative

More information

HPV-Negative Results in Women Developing Cervical Cancer: Implications for Cervical Screening Options

HPV-Negative Results in Women Developing Cervical Cancer: Implications for Cervical Screening Options HPV-Negative Results in Women Developing Cervical Cancer: Implications for Cervical Screening Options R. Marshall Austin MD,PhD Magee-Womens Hospital of University of Pittsburgh Medical Center (UPMC) (raustin@magee.edu)

More information

Evidence-based treatment of a positive HPV DNA test. Th. Agorastos Prof. of Obstetrics & Gynaecology Aristotle University Thessaloniki/GR

Evidence-based treatment of a positive HPV DNA test. Th. Agorastos Prof. of Obstetrics & Gynaecology Aristotle University Thessaloniki/GR Evidence-based treatment of a positive HPV DNA test Th. Agorastos Prof. of Obstetrics & Gynaecology Aristotle University Thessaloniki/GR HPV DNA testing Indications 1. Triage after cytology with ASCUS/LSIL

More information

chapter 4. The effect of oncogenic HPV on transformation zone epithelium

chapter 4. The effect of oncogenic HPV on transformation zone epithelium chapter 4. The effect of oncogenic HPV on transformation zone epithelium CHAPTER 1 All squamous cervical cancer (and probably all cervical adenocarcinoma) is associated with oncogenic HPV, and the absence

More information

EU guidelines for reporting gynaecological cytology

EU guidelines for reporting gynaecological cytology EU guidelines for reporting gynaecological cytology Amanda Herbert Guy s & St Thomas Foundation NHS Trust 5th EFCS Annual Tutorial, Trondheim, Norway 28 th May 1 st June 2012 EU guidelines aim to harmonize

More information

Cervical Precancer: Evaluation and Management

Cervical Precancer: Evaluation and Management TAJ June 2002; Volume 15 Number 1 ISSN 1019-8555 The Journal of Teachers Association RMC, Rajshahi Review fam Cervical Precancer: Evaluation and Management SM Khodeza Nahar Begum 1 Abstract Carcinoma of

More information

The LAST Guidelines in Clinical Practice. Implementing Recommendations for p16 Use

The LAST Guidelines in Clinical Practice. Implementing Recommendations for p16 Use AJCP / Original Article The LAST Guidelines in Clinical Practice Implementing Recommendations for p16 Use Lani K. Clinton, MD, PhD, 1,2 Kyle Miyazaki, 1 Asia Ayabe, 1 James Davis, PhD, 2 Pamela Tauchi-Nishi,

More information

Partha Basu M.D. Screening Group/ Early Detection & Prevention Section

Partha Basu M.D. Screening Group/ Early Detection & Prevention Section Current Status of Quality Assured Colposcopy Practice in South Asia Partha Basu M.D. Screening Group/ Early Detection & Prevention Section Disclosures No financial disclosure NO conflict of interest to

More information

Development and Duration of Human Papillomavirus Lesions, after Initial Infection

Development and Duration of Human Papillomavirus Lesions, after Initial Infection MAJOR ARTICLE Development and Duration of Human Papillomavirus Lesions, after Initial Infection Rachel L. Winer, 1 Nancy B. Kiviat, 2 James P. Hughes, 3 Diane E. Adam, 1 Shu-Kuang Lee, 3 Jane M. Kuypers,

More information

How invasive cervical cancer audit affects clinical practice

How invasive cervical cancer audit affects clinical practice How invasive cervical cancer audit affects clinical practice Referring to NHSCSP and EU guidelines and audits in Southampton and London Amanda Herbert Guy s & St Thomas Foundation NHS Trust How invasive

More information

Understanding Your Pap Test Results

Understanding Your Pap Test Results Understanding Your Pap Test Results Most laboratories in the United States use a standard set of terms called the Bethesda System to report pap test results. Normal: Pap samples that have no cell abnormalities

More information

The Korean Journal of Cytopathology 15 (1) : 17-27, 2004

The Korean Journal of Cytopathology 15 (1) : 17-27, 2004 5 The Korean Journal of Cytopathology 5 () : 7-7, / 5 / / (human papillomavirus, HPV), 6%, 5% HPV. HPV HPV. HPV HPV,,5 HPV HPV. HPV, 6 HPV. HPV HPV International Agency for Research on Cancer (IARC) HPV

More information

Supplements to the European Guidelines on Prevention of Cervical Cancer

Supplements to the European Guidelines on Prevention of Cervical Cancer Asturias, 23 October, 2011 Asturias, 23 October Supplements to the European Guidelines on Prevention of Cervical Cancer M. Arbyn Unit Cancer Epidemiology, IPH, Brussels, Belgium Rue Juliette Wytsmanstraat

More information

LLETZ (Large Loop Excision of the Transformation Zone) Fragmentation: Impact on Margin Assessment and Cervical Biopsy-LLETZ Correlation

LLETZ (Large Loop Excision of the Transformation Zone) Fragmentation: Impact on Margin Assessment and Cervical Biopsy-LLETZ Correlation LLETZ (Large Loop Excision of the Transformation Zone) Fragmentation: Impact on Margin Assessment and Cervical Biopsy-LLETZ Correlation Bridget Melley BSc. (Hons.) in Medical Science Galway-Mayo Institute

More information

Cervical Cancer Screening for the Primary Care Physician for Average Risk Individuals Clinical Practice Guidelines. June 2013

Cervical Cancer Screening for the Primary Care Physician for Average Risk Individuals Clinical Practice Guidelines. June 2013 Cervical Cancer Screening for the Primary Care Physician for Average Risk Individuals Clinical Practice Guidelines General Principles: Since its introduction in 1943, Papanicolaou (Pap) smear is widely

More information

The contribution of MIB 1 in the accurate grading of vulvar intraepithelial neoplasia

The contribution of MIB 1 in the accurate grading of vulvar intraepithelial neoplasia 820 Department of Pathology, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands M van Beurden AJMdeCraen HCWdeVet J L G Blaauwgeers P Drillenburg M P W Gallee N W de Kraker F B

More information

Safe, Confident, QIAsure

Safe, Confident, QIAsure Safe, Confident, QIAsure A new cervical cancer screening test Sample to Insight QIAsure: A breakthrough solution in Women s Health We are at a turning point in the battle against cervical cancer. The global

More information

An Update on Cervical Cancer Screening Recommendations and on the DOH BCC Program

An Update on Cervical Cancer Screening Recommendations and on the DOH BCC Program An Update on Cervical Cancer Screening Recommendations and on the DOH BCC Program Susan Baum, MD, MPH NM Nurse Practitioner Council Annual Conference April 20, 2012 I have no commercial relationships related

More information

Cervical Cancer Screening. David Quinlan December 2013

Cervical Cancer Screening. David Quinlan December 2013 Cervical Cancer Screening David Quinlan December 2013 Cervix Cervical Cancer Screening Modest variation provincially WHO and UK begin at 25 stop at 60 Finland begin at 30 stop at 60 Rationale for

More information

ASCCP 2013 Guidelines for Managing Abnormal Cervical Cancer Screening Tests

ASCCP 2013 Guidelines for Managing Abnormal Cervical Cancer Screening Tests ASCCP 2013 Guidelines for Managing Abnormal Cervical Cancer Screening Tests www.treatmentok.com Barbara S. Apgar, MD, MS Professor of Family Medicine University of Michigan Ann Arbor, Michigan Disclosures

More information

Absolute Risk of a Subsequent Abnormal Pap among Oncogenic Human Papillomavirus DNA-Positive, Cytologically Negative Women

Absolute Risk of a Subsequent Abnormal Pap among Oncogenic Human Papillomavirus DNA-Positive, Cytologically Negative Women Absolute Risk of a Subsequent Abnormal Pap among Oncogenic Human Papillomavirus DNA-Positive, Cytologically Negative Women 2145 Philip E. Castle, Ph.D., M.P.H. 1 Sholom Wacholder, Ph.D. 1 Mark E. Sherman,

More information

Objectives. I have no financial interests in any product I will discuss today. Cervical Cancer Screening Guidelines: Updates and Controversies

Objectives. I have no financial interests in any product I will discuss today. Cervical Cancer Screening Guidelines: Updates and Controversies Cervical Cancer Screening Guidelines: Updates and Controversies I have no financial interests in any product I will discuss today. Jody Steinauer, MD, MAS University of California, San Francisco Objectives

More information

CME/SAM. Follow-up Outcomes in a Large Cohort of Patients With Human Papillomavirus Negative ASC-H Cervical Screening Test Results

CME/SAM. Follow-up Outcomes in a Large Cohort of Patients With Human Papillomavirus Negative ASC-H Cervical Screening Test Results Anatomic Pathology / HPV-Negative ASC-H Follow-up Outcomes in a Large Cohort of Patients With Human Papillomavirus Negative ASC-H Cervical Screening Test Results David Cohen, MD, R. Marshall Austin, MD,

More information

Cervicovaginal Cytology: Normal and Abnormal Cells and Adequacy of Specimens

Cervicovaginal Cytology: Normal and Abnormal Cells and Adequacy of Specimens Cervicovaginal Cytology: Normal and Abnormal Cells and Adequacy of Specimens 3 Christine Bergeron, MD, PhD Introduction Carcinoma of the cervix is a slow growing cancer, which is preceded by precancerous

More information

Screening for Cervical Cancer: A Decision Analysis for the U.S. Preventive Services Task Force

Screening for Cervical Cancer: A Decision Analysis for the U.S. Preventive Services Task Force Screening for Cervical Cancer: A Decision Analysis for the U.S. Preventive Services Task Force Prepared for: Agency for Healthcare Research and Quality U.S. Department of Health and Human Services 540

More information

Long-Term Outcome and Relative Risk in Women With Atypical Squamous Cells of Undetermined Significance

Long-Term Outcome and Relative Risk in Women With Atypical Squamous Cells of Undetermined Significance Anatomic Pathology / LONG-TERM OUTCOME WITH ATYPICAL SQUAMOUS CELLS OF UNDETERMINED SIGNIFICANCE Long-Term Outcome and Relative Risk in Women With Atypical Squamous Cells of Undetermined Significance Stephen

More information

Evaluation of Low-Grade Squamous Intraepithelial Lesions, Cannot Exclude High-Grade Squamous Intraepithelial Lesions on Cervical Smear

Evaluation of Low-Grade Squamous Intraepithelial Lesions, Cannot Exclude High-Grade Squamous Intraepithelial Lesions on Cervical Smear The Korean Journal of Pathology 2010; 44: 528-35 DOI: 10.4132/KoreanJPathol.2010.44.5.528 Evaluation of Low-Grade Squamous Intraepithelial Lesions, Cannot Exclude High-Grade Squamous Intraepithelial Lesions

More information

Triage of Women with Minor Cervical Lesions: Data Suggesting a Test and Treat Approach for HPV E6/E7 mrna Testing

Triage of Women with Minor Cervical Lesions: Data Suggesting a Test and Treat Approach for HPV E6/E7 mrna Testing Triage of Women with Minor Cervical Lesions: Data Suggesting a Test and Treat Approach for HPV E6/E7 mrna Testing Sveinung Wergeland Sørbye 1 *, Silje Fismen 1, Tore Gutteberg 2,3, Elin Synnøve Mortensen

More information

A Cytologic/Histologic Review of 367 Cases. Original Article. Cancer Cytopathology August 25,

A Cytologic/Histologic Review of 367 Cases. Original Article. Cancer Cytopathology August 25, Correlation Between Hybrid Capture II High-Risk Human Papillomavirus DNA Test Chemiluminescence Intensity From Cervical Samples With Follow-Up Histologic Results A Cytologic/Histologic Review of 367 Cases

More information

Molecular Analysis in the Diagnosis and Management of Lesions of Uterine Cervix: The 95% solution. Mark H. Stoler, MD PSC Symposium USCAP 2008

Molecular Analysis in the Diagnosis and Management of Lesions of Uterine Cervix: The 95% solution. Mark H. Stoler, MD PSC Symposium USCAP 2008 Molecular Analysis in the Diagnosis and Management of Lesions of Uterine Cervix: The 95% solution Mark H. Stoler, MD PSC Symposium USCAP 2008 Objectives: This presentation will briefly review the currently

More information

Clinical Practice Guidelines June 2013

Clinical Practice Guidelines June 2013 Clinical Practice Guidelines June 2013 General Principles: The Papanicolaou (Pap) smear is widely credited with reducing mortality from cervical cancer, and remains the single best method for the early

More information

Human Papillomavirus and Papanicolaou Tests to Screen for Cervical Cancer

Human Papillomavirus and Papanicolaou Tests to Screen for Cervical Cancer original article Human Papillomavirus and Papanicolaou Tests to Screen for Cervical Cancer Pontus Naucler, M.D., Ph.D., Walter Ryd, M.D., Sven Törnberg, M.D., Ph.D., Anders Strand, M.D., Ph.D., Göran Wadell,

More information

Cervical Cancer Screening

Cervical Cancer Screening Todd R. Jenkins, MD, MSHA Senior Vice Chair Director, Division of Women s Reproductive Healthcare Learning Objectives Describe the etiology, natural history, and usage of the human papillomavirus (HPV)

More information

Abstract. Human papillomavirus (HPV) DNA testing is cost-effective 1-3 (S. Kulasingam, PhD, et al, unpublished Atypical

Abstract. Human papillomavirus (HPV) DNA testing is cost-effective 1-3 (S. Kulasingam, PhD, et al, unpublished Atypical Anatomic Pathology / HPV DNA DETECTION IN ALTS A Comparison of a Prototype PCR Assay and Hybrid Capture 2 for Detection of Carcinogenic Human Papillomavirus DNA in Women With Equivocal or Mildly Abnormal

More information

HUMAN PAPILLOMAVIRUS TESTING

HUMAN PAPILLOMAVIRUS TESTING CLINICAL GUIDELINES For use with the UnitedHealthcare Laboratory Benefit Management Program, administered by BeaconLBS HUMAN PAPILLOMAVIRUS TESTING Policy Number: PDS - 016 Effective Date: October 1, 2018

More information

RESEARCH ARTICLE. Abstract. Introduction

RESEARCH ARTICLE. Abstract. Introduction DOI:http://dx.doi.org/10.7314/APJCP.2015.16.16.6857 Cost-Effectiveness of Strategies for Detection CIN2+ in Women with ASC-US Pap Smears in Thailand RESEARCH ARTICLE Cost-Effectiveness Analysis of Different

More information

Clinical Relevance of HPV Genotyping. A New Dimension In Human Papillomavirus Testing. w w w. a u t o g e n o m i c s. c o m

Clinical Relevance of HPV Genotyping. A New Dimension In Human Papillomavirus Testing. w w w. a u t o g e n o m i c s. c o m Clinical Relevance of HPV Genotyping A New Dimension In Human Papillomavirus Testing Human Papillomavirus: Incidence HPV prevalence was 26.8% for women in US aged 14 59 yrs 1 20 million Americans are currently

More information

Should Anal Pap Smears Be a Standard of Care in HIV Management?

Should Anal Pap Smears Be a Standard of Care in HIV Management? Should Anal Pap Smears Be a Standard of Care in HIV Management? Gordon Dickinson, M.D., FACP Professor of Medicine and Chief Infectious Diseases, Miller School of Medicine Short Answer: NO But 15-20 HPV

More information

I have no financial interests in any product I will discuss today.

I have no financial interests in any product I will discuss today. Cervical Cancer Screening Update and Implications for Annual Exams George F. Sawaya, MD Professor Department of Obstetrics, Gynecology and Reproductive Sciences Department of Epidemiology and Biostatistics

More information

difficult and may not be practical. Nevertheless, the performance characteristics of rapid screening have not been completely characterized.

difficult and may not be practical. Nevertheless, the performance characteristics of rapid screening have not been completely characterized. Anatomic Pathology / PERFORMANCE CHARACTERISTICS OF RAPID PRESCREENING Performance Characteristics of Rapid (0-Second) Prescreening Implications for Calculating the False-Negative Rate and Comparison With

More information

Abnormal Spectroscopy Scans May Presage Persistent or Progressive Cervical Dysplasia

Abnormal Spectroscopy Scans May Presage Persistent or Progressive Cervical Dysplasia Abnormal Spectroscopy Scans May Presage Persistent or Progressive Cervical Dysplasia Leo B. Twiggs, M.D. Professor Emeritus University of Miami Miller School of Medicine Miami Florida USA Currently- Women

More information

Usefulness of p16/ki67 Immunostaining in the Triage of Women Referred to Colposcopy

Usefulness of p16/ki67 Immunostaining in the Triage of Women Referred to Colposcopy Usefulness of p16/ki67 Immunostaining in the Triage of Women Referred to Colposcopy Jaume Ordi, MD, PhD 1 ; Amaia Sagasta, MD 1 ; Meritxell Munmany, MD 2 ; Leonardo Rodrıguez-Carunchio, MD 1 ; Aureli Torne,

More information

Cervical cancer screening in vaccinated population

Cervical cancer screening in vaccinated population Cervical cancer screening in vaccinated population Cytology and molecular testing Prof. Dr. Fuat Demirkıran I.U Cerrahpaşa School of Medicine. Department of OB&GYN Division Of Gynocol Oncol Izmir, November

More information

Abstract. Anatomic Pathology / p16 Cytology for ASC-US and LSIL Triage

Abstract. Anatomic Pathology / p16 Cytology for ASC-US and LSIL Triage Anatomic Pathology / p16 Cytology for ASC-US and LSIL Triage The Sensitivity and Specificity of p16 INK4a Cytology vs HPV Testing for Detecting High-Grade Cervical Disease in the Triage of ASC-US and LSIL

More information

BRITISH COLUMBIA S CERVICAL CANCER SCREENING PROGRAM

BRITISH COLUMBIA S CERVICAL CANCER SCREENING PROGRAM BRITISH COLUMBIA S CERVICAL CANCER SCREENING PROGRAM DATE: NOVEMBER 19, 2016 PRESENTER: DR. DIRK VAN NIEKERK 1 Conflict of Interest Disclosure Nothing to disclose 2 ..in the beginning of the malady it

More information

Taking Laboratory Coding for a Spin. Corrie Alvarez, CPC, CPMA, CPC-I, CEDC

Taking Laboratory Coding for a Spin. Corrie Alvarez, CPC, CPMA, CPC-I, CEDC Taking Laboratory Coding for a Spin Corrie Alvarez, CPC, CPMA, CPC-I, CEDC Agenda Overview of Laboratory Discuss Common Laboratory Terms Coding Guidelines Review Drug Testing, Anatomical Pathology Discuss

More information

CINtec PLUS and the Pap smear: a co-testing alternative

CINtec PLUS and the Pap smear: a co-testing alternative CINtec PLUS and the Pap smear: a co-testing alternative Rosemary Tambouret MD p16/ki67 (CINtec PLUS) and the Pap smear Rosemary Tambouret MD CINtec PLUS dual stain: p16 and Ki67 p16 is anti-proliferative

More information

CME/SAM. High-Risk HPV Testing in Women 30 Years or Older With Negative Papanicolaou Tests Initial Clinical Experience With 18-Month Follow-up

CME/SAM. High-Risk HPV Testing in Women 30 Years or Older With Negative Papanicolaou Tests Initial Clinical Experience With 18-Month Follow-up Anatomic Pathology / HPV Testing in Negative Papanicolaou Tests High-Risk HPV Testing in Women 30 Years or Older With Negative Papanicolaou Tests Initial Clinical Experience With 18-Month Follow-up Michael

More information

Pap plus HPV every 3 years with screening stopped at 65, 75 and 100 years; Pap plus HPV every 2 years with screening stopped at 65, 75 and 100 years.

Pap plus HPV every 3 years with screening stopped at 65, 75 and 100 years; Pap plus HPV every 2 years with screening stopped at 65, 75 and 100 years. Benefits and costs of using HPV testing to screen for cervical cancer Mandelblatt J S, Lawrence W F, Womack S M, Jacobsen D, Yo B, Hwang Y, Gold K, Barter J, Shah K Record Status This is a critical abstract

More information

King s Research Portal

King s Research Portal King s Research Portal DOI: 10.1111/cyt.12259 Document Version Publisher's PDF, also known as Version of record Link to publication record in King's Research Portal Citation for published version (APA):

More information

NILM Pap Slides From Women 30 Years of Age and Older With Positive High-Risk HPV DNA

NILM Pap Slides From Women 30 Years of Age and Older With Positive High-Risk HPV DNA NILM Pap Slides From Women 30 Years of Age and Older With Positive High-Risk HPV DNA Focused Rescreening Prior to Report Issuance, An Enhanced Quality Control Measure Karen Cormier, CT(ASCP), 1 Michael

More information