title: Comparison of cytology, HPV DNA testing and HPV 16/18 genotyping alone or combined targeting to the more balanced methodology for cervical cancer screening.
abstract: The objective of the present study was to identify the most effective cervical cancer screening algorithm incorporating different combinations of cytology, HPV testing and genotyping.
  
  
  
  Women 25-55years old recruited for the "HERMES" (HEllenic Real life Multicentric cErvical Screening) study were screened in terms of cytology and high-risk (hr) HPV testing with HPV 16/18 genotyping. Women positive for cytology or/and hrHPV were referred for colposcopy, biopsy and treatment. Ten screening algorithms based on different combinations of cytology, HPV testing and HPV 16/18 genotyping were investigated in terms of diagnostic accuracy.
  
  
  
  Three clusters of algorithms were formed according to the balance between effectiveness and harm caused by screening. The cluster showing the best balance included two algorithms based on co-testing and two based on HPV primary screening with HPV 16/18 genotyping. Among these, hrHPV testing with HPV 16/18 genotyping and reflex cytology (atypical squamous cells of undetermined significance - ASCUS threshold) presented the optimal combination of sensitivity (82.9%) and specificity relative to cytology alone (0.99) with 1.26 false positive rate relative to cytology alone.
  
  
  
  HPV testing with HPV 16/18 genotyping, referring HPV 16/18 positive women directly to colposcopy, and hrHPV (non 16/18) positive women to reflex cytology (ASCUS threshold), as a triage method to colposcopy, reflects the best equilibrium between screening effectiveness and harm. Algorithms, based on cytology as initial screening method, on co-testing or HPV primary without genotyping, and on HPV primary with genotyping but without cytology triage, are not supported according to the present analysis.
authors.affiliation: 2nd Department of Obstetrics and Gynecology, Hippokratio Hospital of Thessaloniki, 49 Konstantinoupoleos St, 54642 Thessaloniki, Greece; 4th Department of Obstetrics and Gynecology, Hippokratio Hospital of Thessaloniki, 49 Konstantinoupoleos St, 54642 Thessaloniki, Greece. Electronic address: kimon.chatzistamatiou@gmail.com.
authors.forename: Kimon
authors.initials: K
authors.lastname: Chatzistamatiou
authors.affiliation: Institute of Applied Biosciences, Centre for Research & Technology - Hellas, 57001 Thessaloniki, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Moysiadis
authors.affiliation: 2nd Department of Obstetrics and Gynecology, Hippokratio Hospital of Thessaloniki, 49 Konstantinoupoleos St, 54642 Thessaloniki, Greece; 3rd Department of Obstetrics and Gynecology, Hippokratio Hospital of Thessaloniki, 49 Konstantinoupoleos St, 54642 Thessaloniki, Greece; 4th Department of Obstetrics and Gynecology, Hippokratio Hospital of Thessaloniki, 49 Konstantinoupoleos St, 54642 Thessaloniki, Greece.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Moschaki
authors.affiliation: 2nd Department of Obstetrics and Gynecology, Hippokratio Hospital of Thessaloniki, 49 Konstantinoupoleos St, 54642 Thessaloniki, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Panteleris
authors.affiliation: 4th Department of Obstetrics and Gynecology, Hippokratio Hospital of Thessaloniki, 49 Konstantinoupoleos St, 54642 Thessaloniki, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Agorastos
mesh_terms: D000465:Algorithms; D004279:DNA, Viral / Q000032:analysis* / Q000235:genetics; D066264:Datasets as Topic; D005260:Female; D005838:Genotype; D052162:Human papillomavirus 16 / Q000235:genetics* / Q000302:isolation & purification; D052161:Human papillomavirus 18 / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000473:pathology / Q000821:virology
chemical_list: D004279:DNA, Viral
keywords: Cervical Intraepithelial Neoplasia; Cervical cancer screening; HPV genotyping; HPV testing; Human papillomavirus; Triage to colposcopy