Comparison of biopsy results of HPV 16/18 and non-16/18 HPV positive patients with a normal PAP test, a tertiary center experience

Year 2021, , 41 - 45, 01.01.2021

Kazibe Koyuncu , Mustafa Kurt , Önder Sakin , Emine Eda Akalın , Ramazan Denizli , Abdülmecit Öktem , Yasemin Alan , Mustafa Gökkaya

https://doi.org/10.28982/josam.855308

Cited By: 1

Abstract

Background/Aim: Optimal management for HPV positive and cytology negative patients remains a controversial issue. Immediate colposcopy is suggested for HPV 16/18 positive patients, whereas patients with non 16/18 HPV oncogenic virus positive are recommended to co-test after a year. In this study, we aim to compare the immediate colposcopic biopsy results between HPV 16/18 and non-16/18 HPV positive patients with cytology negative patients.
Methods: In this prospective cross-sectional study, we included 1028 HPV positive and cytology negative patients who were screened for cervical cancer between January 2017 and 2019. Liquid based preparations were used for cytology samples (ThinPrep Pap Test). Cervical specimens were analyzed with Hybrid Capture for HPV types. Patients underwent colposcopic examination, biopsy procedure and endocervical curettage.
Results: A total of 424 (41.2%) patients were HPV 16/18 positive, while 604 (58.8%) were non-16/18 oncologic HPV positive. Colposcopic biopsy results of the patients revealed that of the HPV 16/18 positive patients, 246 (23.9) had no dysplasia, 101 (9.8) had LGSIL and 77 (7.5%) had HGSIL. Among the non 16/18 positive patients, 422 (41.1%) had no dysplasia, 144 (14%) had LGSIL and 38 (3.7) had HGSIL. All patients were referred for endocervical curettage, which resulted as follows: Among HPV 16/18 patients, 384 (37.4%) had no dysplasia, 21 (2%) had LGSIL and 19 (1.8%) had HGSIL. Five hundred seventy-one non 16/18 positive patients had no dysplasia, 26 (2.5%) had LGSIL and 7 (0.7) had HGSIL. The comparison of colposcopic biopsy results of HPV 16/18 and non-16/18 HPV positive patients were different in terms of no dysplasia and HGSIL (P=0.001 and P=0.001, respectively), while LGSIL results were similar. The endocervical curettage biopsy results of the patients revealed a significant difference in HGSIL results (P=0.03). The two groups were similar with respect to reports of no dysplasia and LGSIL.
Conclusion: Direct referral of the patients, who are expected to be lost to follow-up, could be convenient for non-16/18 HPV positive patients with negative cytology to reduce progression of cervical cancer and the psychological burden of HPV positivity.

Keywords

HPV 16, HPV 18, colposcopy, PAP test

References

• 1. de Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B, et al. Retrospective International Survey and HPV Time Trends Study Group. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncology. 2010;11(11):1048-56. Epub 2010/10/15. doi: 10.1016/S1470-2045(10)70230-8. Pubmed PMID: 20952254.
• 2. Tilston P. Anal human papillomavirus and anal cancer. Journal of Clinical Pathology. 1997;50(8):625-34. doi: 10.1136/jcp.50.8.625. Pubmed PMID: 9301544.
• 3. Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92(9):709-20. doi:10.1093/jnci/92.9.709. PMID: 10793107.
• 4. Thomsen LT, Kjær SK, Munk C, Frederiksen K, Ørnskov D, Waldstrøm M. Clinical Performance of Human Papillomavirus (HPV) Testing versus Cytology for Cervical Cancer Screening: Results of a Large Danish Implementation Study. Clinical Epidemiology. 2020;12:203-13. Epub:2020/2/21 doi: 10.2147/CLEP.S243546. Pubmed PMID: 32110112
• 5. Pepe MS, Feng Z, Janes H, Bossuyt PM, Potter JD. Pivotal evaluation of the accuracy of a biomarker used for classification or prediction: standards for study design. Journal of National Cancer Institute. 2008;100(20):1432-8. Epub: 2008/10/7. doi: 10.1093/jnci/djn326. PMID: 18840817
• 6. Pepe MS, Etzioni R, Feng Z, Potter JD, Thompson ML, Thornquist M, et al. Phases of biomarker development for early detection of cancer. Journal of National Cancer Institute. 2001;93(14):1054-61. doi: 10.1093/jnci/93.14.1054. PMID: 11459866.
• 7. Katki HA, Kinney WK, Fetterman B, Lorey T, Poitras NE, Cheung L, et al. Cervical cancer risk for women undergoing concurrent testing for human papillomavirus and cervical cytology: a population-based study in routine clinical practice. Lancet Oncology. 2011;12(7):663-72. doi: 10.1016/S1470-2045(11)70145-0. PMID: 21684207
• 8. Cuzick J, Szarewski A, Cubie H, Hulman G, Kitchener H, Luesley D, et al.Management of women who test positive for high-risk types of human papillomavirus: the HART study. Lancet. 2003 6;362(9399):1871-6 PMID: 14667741
• 9. Wright TC Jr, Massad LS, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D; 2006 ASCCP-Sponsored Consensus Conference. 2006 consensus guidelines for the management of women with abnormal cervical screening tests. Journal of Low Genital Tract Disease. 2007;11(4):201-22. doi: 10.1097/LGT.0b013e3181585870. PMID: 17917566.
• 10. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International Journal of Cancer. 2015;136(5):E359-86. Epub: 2014/10/9. doi: 10.1002/ijc.29210. PMID: 25220842.
• 11. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA A Cancer Journal for Clinicians. 2015;65(2):87-108. Epub 2015/2/4. doi: 10.3322/caac.21262. PMID: 25651787.
• 12. Seneldir H, Kir G. Prevalence of high-risk human papilloma virus in liquid-based cervical samples from Turkish women with normal and abnormal cytology. Diagnostic Cytopathology. 2019;47(2):100-4. Epub 2018/11/20. doi: 10.1002/dc.24022. PMID: 30457213.
• 13. Castle PE, Stoler MH, Wright TC Jr, Sharma A, Wright TL, Behrens CM. Performance of carcinogenic human papillomavirus (HPV) testing and HPV16 or HPV18 genotyping for cervical cancer screening of women aged 25 years and older: a subanalysis of the ATHENA study. Lancet Oncology. 2011;12(9):880-90. Epub 2011/8/22. doi: 10.1016/S1470-2045(11)70188-7. PMID: 21865084.
• 14. Kitchener HC, Almonte M, Thomson C, Wheeler P, Sargent A, Stoykova B, et al. HPV testing in combination with liquid-based cytology in primary cervical screening (ARTISTIC): a randomised controlled trial. Lancet Oncology. 2009;10(7):672-82. Epub 2009/6/17doi: 10.1016/S1470-2045(09)70156-1. PMID: 19540162.
• 15. Massad LS, Einstein MH, Huh WK, Katki HA, Kinney WK, Schiffman M, et al; 2012 ASCCP Consensus Guidelines Conference. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstetrics& Gynecology. 2013;121(4):829-46. doi:10.1097/AOG.0b013e3182883a34. PMID: 23635684.
• 16. Rijkaart DC, Berkhof J, Rozendaal L, van Kemenade FJ, Bulkmans NW, Heideman DA et al. Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial. Lancet Oncology. 2012;13(1):78-88. Epub 2011/12/14. doi: 10.1016/S1470-2045(11)70296-0. PMID: 22177579.
• 17. Arbyn M, Ronco G, Anttila A, Meijer CJ, Poljak M, Ogilvie G, et al cancer. Vaccine. 2012;30 Suppl 5:F88-99. doi: 10.1016/j.vaccine.2012.06.095.PMID: 23199969.
• 18. Castle PE, Sideri M, Jeronimo J, Solomon D, Schiffman M. Risk assessment to guide the prevention of cervical cancer. American Journal of Obstetric and Gynecology. 2007;197(4):356.e1-6. doi: 10.1016/j.ajog.2007.07.049. PMID: 17904958.
• 19. Rijkaart DC, Berkhof J, van Kemenade FJ, Coupe VM, Hesselink AT, Rozendaal L, et al. Evaluation of 14 triage strategies for HPV DNA-positive women in population-based cervical screening. International Journal of Cancer. 2012;130(3):602-10. Epub: 2011/5/5. doi: 10.1002/ijc.26056. PMID: 21400507.
• 20. Tainio K, Athanasiou A, Tikkinen KAO, Aaltonen R, Cárdenas J, Hernándes, et al. Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and meta-analysis. British Medical Journal. 2018;360:k499. doi: 10.1136/bmj.k499. PMID: 29487049.
• 21. Rijkaart DC, Berkhof J, van Kemenade FJ, Coupe VM, Rozendaal L, Heideman DA, et al. HPV DNA testing in population-based cervical screening (VUSA-Screen study): results and implications. British Journal of Cancer. 2012;106(5):975-81. Epub: 2012/1/17doi: 10.1038/bjc.2011.581. PMID: 22251922; PMCID.
• 22. Wentzensen N, Fetterman B, Castle PE, Schiffman M, Wood SN, Stiemerling E, et al. p16/Ki-67 Dual Stain Cytology for Detection of Cervical Precancer in HPV-Positive Women. Journal of the National Cancer Institute. 2015;107(12):djv257. doi: 10.1093/jnci/djv257. PMID: 26376685;
• 23. Gustinucci D, Giorgi Rossi P, Cesarini E, Broccolini M, Bulletti S, Carlani A, et al. Use of Cytology, E6/E7 mRNA, and p16INK4a-Ki-67 to Define the Management of Human Papillomavirus (HPV)-Positive Women in Cervical Cancer Screening. American Journal of Clinical Pathology. 2016;145(1):35-45. doi:10.1093/ajcp/aqv019. PMID: 26712869.
• 24. Luttmer R, Dijkstra MG, Snijders PJ, Berkhof J, van Kemenade FJ, Rozendaal L, et al. p16/Ki-67 dual-stained cytology for detecting cervical (pre)cancer in a HPV-positive gynecologic outpatient population. Modern Pathology. 2016;29(8):870-8. Epub:2016/5/6. doi: 10.1038/modpathol.2016.80. PMID: 27150161.
• 25. American Society for Colposcopy and Cervical Pathology HPV genotyping clinical update 2009 http://www.asccp.org/consensus.
• 26. Baser E, Togrul C, Ozgu E, Esercan A, Caglar M, Gungor T. Effect of pre-procedural state-trait anxiety on pain perception and discomfort in women undergoing colposcopy for cervical cytological abnormalities. Asian Pacific Journal of Cancer Prevention. 2013;14(7):4053-6. doi: 10.7314/apjcp.2013.14.7.4053. PMID: 23991951.
• 27. Mandriota SJ, Tenan M, Ferrari P, Sappino AP. Aluminium chloride promotes tumorigenesis and metastasis in normal murine mammary gland epithelial cells. International Journal of Cancer. 2016;139(12):2781-90. Epub:2016/9/7doi: 10.1002/ijc.30393.. PMID: 27541736.
• 28. Schiffman M, Hyun N, Raine-Bennett TR, Katki H, Fetterman B, Gage JC, et al. A cohort study of cervical screening using partial HPV typing and cytology triage. International Jorunal of Cancer. 2016;139(11):2606-15. Epub: 2016/9/26. doi: 10.1002/ijc.30375. PMID: 27509172.
• 29. Cox JT, Castle PE, Behrens CM, Sharma A, Wright TC Jr, Cuzick J; Athena HPV Study Group. Comparison of cervical cancer screening strategies incorporating different combinations of cytology, HPV testing, and genotyping for HPV 16/18: results from the ATHENA HPV study. American Journal of Obstetetrics and Gynecology. 2013 Mar;208(3):184.e1-184.e11. Epub: 2012/11/19 doi: 10.1016/j.ajog.2012.11.020. PMID: 23174289.
• 30. Aydoğmuş H, Aydoğmuş S. Comparison of Colposcopic Biopsy Results of Patients Who have Cytomorphological Normal but HPV 16-18 or Other High-Risk HPV Subtypes Positive. Asian Pacific Journal of Cancer Prevention. 2019;20(2):417-20. doi: 10.31557/APJCP.2019.20.2.417. PMID: 30803201
• 31. Denizli R, Sakin O, Anğın D Ali, Cikman MS, Pirimoglu Z. Colposcopic examination in cytology negative women who tested positive for non-16/18 hpv types. İstanbul Tıp Fakültesi Dergisi. 2019;82. 10.26650/IUITFD.2018.0026.
• 32. Karaca İ, Öztürk M, Comba C, Demirayak G, Alay İ, Erdoğan VŞ, et al. Immediate biopsy of cervical cytology-negative and non-HPV-16/18 oncogenic types positive patients. Diagnostic Cytopathology. 2018;46(4):326-30. Epub: 2018/2/19 doi: 10.1002/dc.23905. PMID: 29460502.
• 33. Keser Şahi̇n H, Aslan O, Şahi̇n M. Evaluation of cancer-related deaths in Turkey between 2009-2018: An epidemiological study. J Surg Med. 2020;4(8):674-7.