Geburtshilfe Frauenheilkd 2015; 75(10): 1058-1062
DOI: 10.1055/s-0035-1557841
Original Article
GebFra Science
Georg Thieme Verlag KG Stuttgart · New York

Relevance of HPV Screening for Triaging Equivocal Cytology Findings in the Pap II-p, Pap III and Pap IIID Groups – Results of Two Long-Term Studies

Wertigkeit der HPV-Testung zur Triage unklarer zytologischer Befunde der Gruppen Pap II-p, Pap III und Pap IIID – Ergebnisse zweier Langzeitstudien
A. Luyten
Frauenklinik im Klinikum Wolfsburg, Wolfsburg
,
K. U. Petry
Frauenklinik im Klinikum Wolfsburg, Wolfsburg
› Author Affiliations
Further Information

Publication History

received 19 February 2015
revised 24 June 2015

accepted 24 June 2015

Publication Date:
02 November 2015 (online)

Abstract

Introduction: The use of HPV screening for the triage of ASC-US (atypical squamous cells of undetermined significance) cytology results has been established as a sound standard by international trials whereas the data for other cytology findings are in part contradictory. There is a lack of long-term studies on the use of HPV triage in Germany. Materials and Methods: For the present study data from a primary HPV screening project involving women aged over 30 years, ongoing since 2006, and an epidemiological study on women aged between 20 and 27 years, ongoing since 2009, were used. Upon recruitment, all women underwent a smear test for cytology and screening for “high-risk” HPV using Hybrid Capture 2 (HC2). If both tests were positive or if there were persisting remarkable cytology findings or a positive HPV test, then clarification by colposcopy was performed. Results: Altogether, among 282 women with Pap II-p (ASC-US), Pap III (ASC-H) or Pap IIID (LSIL + CIN2) and negative HPV test there was no case of CIN3+. Among the women under 30 years of age, however, 69 % (ASC-US) to 85 % (LSIL + CIN2) of the remarkable findings were HPV positive, also among the older women with Pap IIID, the 71 % prevalence of HPV was too high for a triage and even without triage there was a 23 % risk for CIN3+. On the other hand, of the women over 30 years old with ASC-US (Pap II-p) findings, only 21 % were positive for HPV and the risk for CIN3+ in this group was high at 29 %. Also for ASC-H (Pap III) findings in the age group of over 30 years with an HPV prevalence of 56 % there was an efficient triage for CIN3+. Discussion: In summary, the HPV triage of ASC-US (Pap II-p) findings in women aged over 30 years was found to be efficient; in contrast, LSIL + CIN2 (Pap IIID) findings in this age group justified an immediate referral to colposcopy whereas cytology control appeared to be sufficient for younger women.

Zusammenfassung

Einleitung: Der Einsatz der HPV-Testung zur Triage von ASC-US-(atypical squamous cells of undetermined significance-)Zytologiebefunden ist ein durch internationale Studien gut belegter Standard, für andere zytologische Befunde gibt es teils widersprüchliche Daten. In Deutschland fehlen bisher Langzeitstudien zum Nutzen der HPV-Triage. Material und Methoden: Für die vorliegende Untersuchung wurden Daten eines seit 2006 laufenden primären HPV-Screening-Projekts bei Frauen über 30 Jahren und einer seit 2009 laufenden epidemiologischen Studie bei Frauen zwischen 20 und 27 Jahren genutzt. Bei allen Frauen wurden bei Rekrutierung Abstriche für Zytologie und Testung auf „high-risk“-HPV mittels Hybrid Capture 2 (HC2) entnommen. Fielen beide Tests positiv aus oder persistierten auffällige zytologische Befunde oder ein positiver HPV-Test, dann erfolgte eine Abklärung mittels Kolposkopie. Ergebnisse: Insgesamt ergab sich bei 282 Frauen mit Pap II-p, Pap III oder Pap IIID und negativem HPV Test kein Fall einer CIN3+. Bei Frauen unter 30 Jahren waren aber 69 % (Pap II-p) bis 85 % (Pap IIID) der auffälligen Befunde HPV-positiv, auch bei älteren Frauen mit Pap IIID ergab sich für eine Triage mit 71 % eine zu hohe HPV-Prävalenz und bereits ohne Triage ein 23 % Risiko für CIN3+. Bei Frauen über 30 Jahren mit Pap-II-p-Befunden waren dagegen nur 21 % HPV-positiv, und das Risiko für CIN3+ war in dieser Gruppe mit 29 % hoch. Auch für Pap-III-Befunde ergab sich in der Altersgruppe über 30 Jahre bei einer HPV-Prävalenz von 56 % für CIN3+ eine effiziente Triage. Diskussion: Zusammenfassend erwies sich die HPV-Triage von Pap-II-p-Befunden bei Frauen über 30 Jahren als effizient, dagegen erschien bei Pap-IIID-Befunden in dieser Altersgruppe die sofortige Überweisung zur Kolposkopie gerechtfertigt während bei jüngeren Frauen die zytologische Kontrolle als ausreichend erschien.

Supporting Information

 
  • References

  • 1 Petry KU, Menton S, Menton M et al. Inclusion of HPV testing in routine cervical cancer screening for women above 29 years in Germany: results for 8466 patients. Br J Cancer 2003; 88: 1570-1577
  • 2 Petry KU, Luyten A, Justus A et al. Prevalence of high-risk HPV types and associated genital diseases in women born in 1988/89 or 1983/84–results of WOLVES, a population-based epidemiological study in Wolfsburg, Germany. BMC Infect Dis 2013; 13: 135
  • 3 Petry KU, Rinnau F, Bohmer G et al. Annual Papanicolaou screening for 5 years among human papillomavirus-negative women. BMC Cancer 2013; 13: 379
  • 4 Moss EL, Arbyn M, Dollery E et al. European Federation of Colposcopy quality standards Delphi consultation. Eur J Obstet Gynecol Reprod Biol 2013; 170: 255-258
  • 5 TOMBOLA Group. Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy: multicentre randomised controlled trial. BMJ 2009; 339: b2548
  • 6 TOMBOLA Group. Options for managing low grade cervical abnormalities detected at screening: cost effectiveness study. BMJ 2009; 339: b2549
  • 7 TOMBOLA Group. Cytological surveillance compared with immediate referral for colposcopy in management of women with low grade cervical abnormalities: multicentre randomised controlled trial. BMJ 2009; 339: b2546
  • 8 Kitchener HC, Fletcher I, Roberts C et al. The psychosocial impact of human papillomavirus testing in primary cervical screening-a study within a randomized trial. Int J Gynecol Cancer 2008; 18: 743-748
  • 9 Petry KU, Böhmer G, Iftner T et al. Factors associated with an increased risk of prevalent and incident grade III cervical intraepithelial neoplasia and invasive cervical cancer among women with Papanicolaou tests classified as grades I or II cervical intraepithelial neoplasia. Am J Obstet Gynecol 2002; 186: 28-34
  • 10 Solomon D, Schiffman M, Tarone R. Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial. J Natl Cancer Inst 2001; 93: 293-299
  • 11 Szarewski A, Ambroisine L, Cadman L et al. Comparison of predictors for high-grade cervical intraepithelial neoplasia in women with abnormal smears. Cancer Epidemiol Biomarkers Prev 2008; 17: 3033-3042
  • 12 Luyten A, Buttmann-Schweiger N, Luyten K et al. Early detection of CIN3 and cervical cancer during long-term follow-up using HPV/Pap smear co-testing and risk-adapted follow-up in a locally organised screening programme. Int J Cancer 2014; 135: 1408-1416
  • 13 Griesser H, Marquardt K, Jordan B et al. Das Prozedere bei auffälligen Befunden. Kommentar zur Münchner Nomenklatur III. Frauenarzt 2015; 56: 10-13
  • 14 Ikenberg H, Bergeron C, Schmidt D et al. Screening for cervical cancer precursors with p 16/Ki-67 dual-stained cytology: results of the PALMS study. J Natl Cancer Inst 2013; 105: 1550-1557
  • 15 Petry KU, Schmidt D, Scherbring S et al. Triaging Pap cytology negative, HPV positive cervical cancer screening results with p 16/Ki-67 Dual-stained cytology. Gynecol Oncol 2011; 121: 505-509
  • 16 Schmidt D, Bergeron C, Denton KJ et al. p 16/ki-67 dual-stain cytology in the triage of ASCUS and LSIL Papanicolaou cytology: results from the European equivocal or mildly abnormal Papanicolaou cytology study. Cancer Cytopathol 2011; 119: 158-166