Objective: Cervical cancer is the number one cause of cancer-associated death in Indonesian women (30/100,000 annually), where no screening program is present. The Papanicolaou test is widely accepted as an effective screening method for cervical neoplasia detection and often shows certain cytological features associated with human papillomavirus (HPV) infection. Especially in developing countries, cytological investigation is still the method of choice as compared to the frequent use of HPV DNA testing in western countries. Study Design: In the present study, we investigated the validity of the use of cytomorphological changes as a marker for HPV infection. A total of 140 smears collected in three different areas in Indonesia (Jakarta, Tasikmalaya and Bali) were analyzed. HPV DNA testing was performed using INNO-LiPA assays. Results and Conclusions: We found a highly significant association of classical koilocytosis, multinucleated cells, dyskeratosis-parakeratosis, nuclear membrane, enlarged nuclei, moderate/strong hyperchromasia and chromatin pattern with HPV positivity. Using classical and nonclassical cytomorphological parameters we found an overall sensitivity of 42% and a specificity of 90%. The combination of classical and nonclassical parameters led to a higher sensitivity of HPV positivity prediction. These results are of importance for cytologists in developing countries as molecular HPV testing still poses a major financial, logistic and expertise problem.

Bosch FX, Lorincz A, Muñoz N, Meijer CJ, Shah KV: The causal relation between human papillomavirus and cervical cancer. Clin Pathol 2002;55:244–265.
Bosch FX, Manos MM, Muñoz N, Sherman M, Jansen AM, Peto J, Schiffman MH, Moreno V, Kurman R, Shah KV: Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. J Natl Cancer Inst 1995;87:796–802.
Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Muñoz N: Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999;189:12–19.
Parkin DW, Pisani P, Ferlay J: Estimates of the worldwide incidence of 25 major cancers in 1990. Int J Cancer 1999;80:827–841.
Tjindarbumi D, Mangunkusumo R: Cancer in Indonesia, present and future. Jpn J Clin Oncol 2002;32(suppl):S17–S21.
Vet JN, de Boer MA, van den Akker BE, Siregar B, Lisnawati, Budiningsih S, Tyasmorowati D, Moestikaningsih, Cornain S, Peters AA, Fleuren GJ: Prevalence of human papillomavirus in Indonesia: a population-based study in three regions. Br J Cancer 2008;99:214–218.
Franco EL, Villa LL, Sobrinho JP, Prado JM, Rousseau MC, Désy M, Rohan TE: Epidemiology of acquisition and clearance of cervical human papillomavirus infection in women from a high-risk area for cervical cancer. J Infect Dis 1999;180:1415–1423.
zur Hausen H: Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2002;2:342–350.
Nobbenhuis MA, Walboomers JM, Helmerhorst TJ, Rozendaal L, Remmink AJ, Risse EK, van der Linden HC, Voorhorst FJ, Kenemans P, Meijer CJ: Relation of human papillomavirus status to cervical lesions and consequences for cervical-cancer screening: a prospective study. Lancet 1999;354:20–25.
Meisels A, Fortin R: Condylomatous lesions of the cervix and vagina. I. Cytologic patterns. Acta Cytol 1976;20:505–509.
Tanaka H, Chua KL, Lindh E, Hjerpe A: Patients with various types of human papillomavirus: covariation and diagnostic relevance of cytological findings in Papanicolaou smears. Cytopathology 1993;4:273–283.
Yamamoto LS, Alves VA, Maeda MY, Longatto-Filho A, Utagawa ML, Eluf Neto J: A morphological protocol and guide-list on uterine cervix cytology associated to Papillomavirus infection. Rev Inst Med Trop Sao Paulo 2004;46:189–193.
Schneider A, Meinhardt G, De-Villiers EM, Gissmann L: Sensitivity of the cytologic diagnosis of cervical condyloma in comparison with HPV-DNA hybridization studies. Diagn Cytopathol 1987;3:250–255.
Cecchini S, Confortini M, Bonardi L, Cipparrone G, Galante L, Iossa A, Ciatto S: ‘Nonclassic’ cytologic signs of cervical condyloma. A case-control study. Acta Cytol 1990;3:781–784.
Bollmann M, Bánkfalvi A, Trosic A, Speich N, Schmitt C, Bollmann R: Can we detect cervical human papillomavirus (HPV) infection by cytomorphology alone? Diagnostic value of non-classic cytological signs of HPV effect in minimally abnormal Pap tests. Cytopathology 2005;16:13–21.
Cramer HM, Wannemuehler SES, Brown DR, Katz BP, Fife KH: Cytomorphologic correlates of human papillomavirus infection in the ‘normal’ cervicovaginal smear, Acta Cytol 1997;41:261–268.
Lorincz AT, Richart RM: Human papillomavirus DNA testing as an adjunct to cytology in cervical screening programs. Arch Pathol Lab Med 2003;127:959–968.
Kleter B, van Doorn LJ, Schrauwen L, Molijn A, Sastrowijoto S, ter Schegget J, Lindeman J, ter Harmsel B, Burger M, Quint W: Development and clinical evaluation of a highly sensitive PCR-reverse hybridization line probe assay for detection and identification of anogenital human papillomavirus. J Clin Microbiol 1999;37:2508–2517.
Munoz N, Bosch FX, de Sanjose S, Herrero R, Castellsague X, Shah KV, Snijders PJ, Meijer CJ: Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003;348:518–527.
ALTS Group: Results of a randomized trial on the management of cytology interpretations of atypical squamous cells of undetermined significance. Am J Obstet Gynecol 2003;188:1383–1392.
Snijders PJ, van den Brule AJ, Meijer CJ: The clinical relevance of papillomavirus testing: relationship between analytical and clinical sensitivity. J Pathol 2003;201:1–6.
Arends MJ, Buckley CH, Wells M: Aetiology, pathogenesis and pathology of cervical neoplasia. J Clin Pathol 1998;51:96–103.
Sherman ME, Schiffman M, Cox JT, ALTS Group: Effects of age and human papilloma viral load on colposcopy triage: data from the randomized Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS). J Natl Cancer Inst 2002;94:102–107.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.