Sitolojileri Normal Kadınlarda Yüksek Riskli Hpv Pozitifliği Varlığında Servikal Patolojilerin Karşılaştırılması

Abstract

Amaç: Servıks kanseri tarama programında Hpv 16-18 tipi pozitif hastalara kolposkopi yapılmaktadır. Smear negatif olan, Tip 16-18 dışı yüksek riskli Hpv pozitifliği olan hastalar 1 yıl sonra kotest ile değerlendirilmektedir. Biz çalışmamız ile kolposkopi yapılan; tip 16-18 Hpv pozitifliği ve tip 16-18 dışı yüksek riskli Hpv pozitifliği olan hastaların sonuçlarını karşılaştırmayı hedefledik. Gereç ve Yöntemler: Sitolojileri normal olan; tip 16-18 dışı HR-HPV tip pozitifliği olan 192 hastanın, kolposkopiye bağlı çıkan histopatolojik bulguları, tip 16-18 HR-HPV pozitifliği olan 217 hastanın kolposkopiye bağlı çıkan histopatolojik bulguları ile karşılaştırdı. Demografik veriler, body mass indeksi (BMI) ve histolojik sınıflandırma ile ilgili veriler kaydedildi. Sonuçlar: Yaş ortalaması 41.6± 8.5, BMI ları 29.2±4.4 idi. Değerlendirilen 409 kadından 217'si HPV tip 16/18 (% 53), 192'si non-16/18 tip (%47) için pozitifti. Tip 16-18 HR-HPV pozitifliği olan kadınlarda yapılan kolposkopik biyopsi sonuçları; normal biyopsi sonucu 147(%67.7), invaziv serviks karsinomu 2(%0.9) olarak saptandı. Tip non-16-18 HR-HPV pozitifliği olan kadınlarda ise normal biyopsi sonucu 159(%83), invaziv serviks karsinomu 1(%0.5) olarak saptandı. Grup 1’de anormal biyopsi sonuçları anlamlı olarak daha fazla idi (p=0.003). Tartışma: HPV 16 ve 18 ile oluşan enfeksiyonlar, CIN 2 veya daha ileri (≥CIN 2) lezyonlar için en yüksek risk ile ilişkilidir. Kolposkopik muayene yaptığımız tip 16/18 HR-HPV hastalarından 2 tanesinde ve non-tip 16/18 HR-HPV hastalarının 1 tanesinde invaziv serviks kanseri saptadık. Bu durum invazive servikal kanseri saptamada kolposkopik yönetim sonuçlarının her iki grupta da farklı olmadığını ve bu şekilde invaziv serviks kanserini erken yakalayabileceğimizi düşündürüyor. Çalışmamızda hasta sayısının az olması nedeniyle bu konuda gelecekte daha kapsamlı çalışmaların yapılması ve kolposkopinin yüksek riskli HPV’nin tüm tiplerinde uygulanabilirliğinin araştırılması gerektiğini düşünmekteyiz.

Keywords

• Yüksek Riskli HPV
• Servical İntraepitelyal Neoplazi
• Servical Neoplasm
• Kolposkopi
• Human Papillomavirus

Comparison of Cervical Pathologies in Presence of High-Risk HPV Positivity in Women with Normal Cytology

Abstract

Aim: Regarding the cervical cancer screening program, who are HPV-16/18 positive, undergo colposcopy. Patients, who have a negative smear but high-risk HPV positivity except for type 16-18, are examined with cotesting one year later. In this study, our objective was to compare the results of patients, who had type 16/18 HPV positivity and non-16/18 HPV positivity. Methods: The results of 409 patients, who had high-risk HPV (HR-HPV) positivity and negative cytology, were evaluated retrospectively. Demographic data, body mass index (BMI) and histological classification were recorded. The histopathological findings obtained with the colposcopic examination in patients (n=192), who had normal cytology and non-16/18 HR-HPV positivity, were compared with the histopathological findings obtained with a colposcopic examination in patients (n=217), who had type 16-18 HR-HPV positivity. Results: The mean age and BMI were 41.6±8.5 years and 29.2±4.4. A total of 409 women were assessed and 217 of them had type 16-18 HR-HPV positivity (53%) and 192 had non-16/18 HR-HPV positivity (47%). The following colposcopic biopsy results were obtained in women with type 16-18 HR-HPV positivity: 147 patients had normal biopsy results (67.7%); 68(31.4%) patients had premalignant cervical lesions and 2 patients had invasive cervix carcinoma (0.9%). Regarding the women with non-16/18 HR-HPV positivity, the colposcopic biopsy results were as follows: 159 patients had normal biopsy results (83%); 32(16.6%) patients had premalignant cervical lesions and 1 patient had invasive cervix carcinoma (0.5%). The rate of abnormal biopsy results was significantly higher in Group1 (p=0.003). Conclusions: Infections caused by HPV16/18, ≥CIN2 lesions are related to high risk. We determined invasive cervix carcinoma in 2 of patients with type 16-18 HR-HPV positivity and in 1 of patients with non-16/18 HR-HPV positivity. Due to the small number of patients in our study, we believe that there is a need for more comprehensive studies and for the investigation of the benefits of the colposcopy in all types of HR-HPV infections.

Keywords

• High-Risk HPV
• Cervical Intraepithelial Neoplasia
• Human Papillomavirus
• Cervical Neoplasm
• Colposcopy

References

1. 1. Walboomers JM, Jacobs MV, Manos MM, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999;189:12-9.
 

2. 2. Bosch FX, de Sanjosé S. Chapter 1: Human papillomavirus and cervical cancer--burden and assessment of causality. J Natl Cancer Inst Monogr 2003;2003:3-13.
 

3. 3. Clifford G, Franceschi S, Diaz M, Muñoz N, Villa LL. Chapter 3: HPV type-distribution in women with and without cervical neoplastic diseases. Vaccine. 2006 Aug 31;24 Suppl 3:S3/26-34. Epub 2006 Jun 2.
4. 4. Huh WK, Ault KA, Chelmow D, et al. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance. Gynecol Oncol 2015;136:178-82.


5. 5. Tota J.E, Bentley J, Blake J, et al., Introduction of molecular HPV testing as the primary technology in cervical cancer screening: acting on evidence to change the current paradigm, Prev. Med. 98 (2017) 5–14. 

6. 6. Lew J.B, Simms K, Smith M, Lewis H, Neal H, Canfell K. Effectiveness modelling and economic evaluation of primary HPV screening for cervical cancer prevention in New Zealand, PLoS One 11 (2016), e0151619. . 

7. 7. Ho G.Y, Bierman R, Beardsley L, Chang C.J, Burk R.D, Natural history of cervicovaginal papillomavirus infection in young women, N. Engl. J. Med. 338 (1998) 423–428. 

8. 8. Arbyn M, de Sanjose S, Saraiya M, et al., EUROGIN 2011 roadmap on prevention and treatment of HPV-related disease, Int. J. Cancer 131 (2012) 1969–1982. 


9. 9. Dong L, Wang MZ, Zhao X, et al. Human papillomavirus viral load as a useful triage tool for non-16/18 high-risk human papillomavirus positive women: A prospective screening cohort study. Gynecologic Oncology 148 (2018) 103–110
10. 10. Zhao F.H, Lin M.J, Chen F, et al., Performance of high- risk human papillomavirus DNA testing as a primary screen for cervical cancer: a pooled analysis of individual patient data from 17 population-based studies from China, Lancet Oncol. 11 (2010) 1160–1171.
11. 11. Naucler P, Ryd W, Tornberg S, et al. Human papillomavirus and Papanicolaou tests to screen for cervical cancer. N Engl J Med 2007;357:1589–97.
12. 12. Mayrand MH, Duarte-Franco E, Rodrigues I, et al. Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. N Engl J Med 2007;357:1579–88.
13. 13. Franceschi S, Denny L, Irwin KL, et al. Eurogin 2010 roadmap on cervical cancer prevention. Int J Cancer 2011;128:2765–74.
14. 14. Bruni L, Diaz M, Castellsagué X, Ferrer E, Bosch FX, de Sanjosé S. Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis. 2010 Dec 15;202(12):1789-99
15. 15. Franco EL, Villa LL, Sobrinho JP, et al. Epidemiology of acquisition and clearance of cervical human papillomavirus infection in women from a high-risk area for cervical cancer. J Infect Dis. 1999 Nov;180(5):1415-23.
16. 16. Ergünay K, Mısırlıoğlu M, Fırat P, et al. Sitolojik Atipi Ġözlenen Servikal Örneklerde İnsan Papilloma Virusunun Polimeraz Zincir Reaksiyonu ve Hibridizasyon Yöntemleriyle Saptanması ve Tiplendirilmesi. Mikrobiyoloji Bülteni, 2008; 42: 273-282
17. 17. Ardıç N, Öztürk O, Ergünay K, Sezer O. Servikal sürüntü örneklerinde yüksek riskli insan papilloma virus tiplerine ait E6/E7 mRNA'larının ticari otomatiza bir NASBA sistemiyle araştırılması. Mikrobiyoloji Bülteni, 2009; 43: 463-469
18. 18. de Villiers EM, Fauquet C, Broker TR, Bernard HU, zur Hausen H. Classification of papillomaviruses. Virology 2004; 324(1): 17-27
19. 19. Muñoz N, Bosch FX, de Sanjosé S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003; 348(6): 518-527.
20. 20. Barbieri D, Nocera M, Gallinella G, et al. Comparison of HPV sign genotyping test with INNO-LiPA HPV genotyping extra assay on histologic and cytologic cervical specimens. Diagn Microbiol Infect Dis. 2012; 74(1): 43-8
21. 21. Cuzick J, Bergeron C, von Knebel Doeberitz M, et al. New technologies and procedures for cervical cancer screening. Vaccine. 2012 Nov 20;30 Suppl 5:F107-16
22. 22. Castle PE, de Sanjosé S, Qiao YL, Belinson JL, Lazcano-Ponce E, Kinney W. Introduction of human papillomavirus DNA screening in the world: 15 years of experience. Vaccine. 2012 Nov 20;30 Suppl 5:F117-22
23. 23. Guan Y, Gravitt PE, Howard R, et al. Agreement for HPV genotyping detection between self-collected specimens on a FTA cartridge and clinician-collected specimens. J Virol Methods. 2013 Apr;189(1):167-71. doi: 10.1016/j.jviromet.2012.11.010. Epub 2013 Jan 29.
24. 24. Bosch FX, Burchell AN, Schiffman M, et al. Epidemiology and natural history of human papillomavirus infections and type-specific implications in cervical neoplasia. Vaccine. 2008 Aug 19;26 Suppl 10:K1-16
25. 25. Saslow D, Solomon D, Lawson HW, et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology. Screening guidelines for the prevention and early detection of cervical cancer. Am J Clin Pathol. 2012 Apr;137(4):516-42
26. 26. Arbyn M, Ronco G, Anttila A, et al. Evidence regarding human papillomavirus testing in secondary prevention of cervical cancer. Vaccine. 2012 Nov 20;30 Suppl 5:F88-99.
27. 27. Kjær SK, Frederiksen K, Munk C, Iftner T. Long-term absolute risk of cervical intraepithelial neoplasia grade 3 or worse following human papillomavirus infection: role of persistence. J Natl Cancer Inst. 2010 Oct 6;102(19):1478-88
28. 28. Berkhof J, Bulkmans NW, Bleeker MC, et al. Human papillomavirus type-specific 18-month risk of high-grade cervical intraepithelial neoplasia in women with a normal or borderline/mildly dyskaryotic smear. Cancer Epidemiol Biomarkers Prev. 2006 Jul;15(7):1268-73.
29. 29. Matsumoto K, Hirai Y, Furuta R, et al. Subsequent risks for cervical precancer and cancer in women with low-grade squamous intraepithelial lesions unconfirmed by colposcopy-directed biopsy: results from a multicenter, prospective, cohort study. Int J Clin Oncol. 2012 Jun;17(3):233-9.
30. 30. Hwang SJ, Shroyer KR. Biomarkers of cervical dysplasia and carcinoma. J Oncol. 2012;2012:507286.