Human Papillomavirüs (HPV), Servikal Smear ve Kolposkopik Biyopsi Sonuçlarının Karşılaştırılması: Serviks Kanseri Taramasında Bir Üniversite Hastanesinin 4 Yıllık Deneyimi

Yıl 2022, Cilt: 19 Sayı: 2, 1295 - 1300, 01.07.2022

Duygu Altın Deha Denizhan Keskin

https://doi.org/10.38136/jgon.1074012

Öz

Amaç: Sitolojinin sensitivitesi görece düşük olduğu için serviks kanseri taramasında Human papillomavirus (HPV) DNA ile tarama önerilmektedir. Bu çalışmanın amacı HPV, servikal smear ve kolposkopik biyopsi sonuçları arasındaki uyumu araştırmaktır.
Gereçler ve Yöntem: Ordu Üniversitesi Eğitim ve Araştırma Hastanesi’nde Ocak 2018-Aralık 2021 yılları arasında kolposkopik biyopsi alınan hastalar geriye dönük taranmıştır. Herhangi bir yüksek riskli HPV pozitifliği olan, servikal smear ve kolposkopik biyopsi sonucu bulunan hastalar çalışmaya dahil edilmiştir. HPV tipleri, smear ve biyopsi sonuçları karşılaştırılmıştır.
Bulgular: Çalışmaya 734 hasta dahil edilmiştir. Hastaların ortalama yaşı 41.9 ± 7.36’dır. 165 (%22.5) hastada tek başına HPV 16, 35 (%4.8) hastada tek başına HPV 18, 354 (%48.2) hastada diğer yüksek riskli HPV tiplerinden biri ve 180 (%24.5) hastada en az iki HPV tipi birlikte tespit edilmiştir. 298 (%40.6) hastada HPV 16 ve/veya HPV 18 tek başına ya da başka tiplerle bir arada bulunmaktadır. Hastaların çoğunda (%55.3) smear sonucu normal iken ASC-US en sık saptanan sitolojik anormallik olmuştur. Kolposkopi eşliğinde alınan biyopsi sonuçları şu şekildedir: 452 (%61.6) normal, 199 (%27.1) CIN 1, 36 (%4.9) CIN 2, 42 (%5.7) CIN 3 ve 5 (%0.7) skuamoz hücreli karsinom. HPV 16 ve/veya HPV 18 olan hastaların %66.1’inde smear sonucu normal olmasına karşın diğer yüksek-riskli HPV subtiplerine göre daha fazla ≥CIN 2 lezyon saptanmıştır (%19.8 vs %5.5, p<0.001). Bir veya daha fazla HPV subtipi ile enfekte olmakla lezyon şiddeti arasında istatistiksel olarak anlamlı bir fark yoktur (p=0.474). Smear testinin sensitivitesi %55.2, spesifisitesi %69.2 olarak bulunmuştur.
Sonuç: HPV 16 ve/veya HPV 18 ile enfekte olan hastaların smear sonuçları çoğunlukla normal olsa da bu hastaların yaklaşık %20’sınde ≥CIN 2 lezyon bulunmaktadır. Smear testinin sensitivitesi düşük olduğundan HPV genotiplendirme ile tarama daha güvenilir bir yöntemdir.

Anahtar Kelimeler

Human papillomavirus DNA testi, servikal smear, kolposkopi, serviks kanseri taraması

Relationship Between Human Papillomavirus (HPV), Cervical Smear Cytology and Colposcopy Directed Biopsy Results: 4 Year Experience of a University Hospital in Cervical Cancer Screening

Öz

Aim: Cervical cancer screening guidelines gradually recommend human papillomavirus (HPV) DNA testing since sensitivity of cytology is relatively low. This study aimed to evaluate correlation between HPV, cervical smear cytology and colposcopy directed biopsy results.
Material and Methods: Patients who underwent colposcopy directed biopsy in Ordu University Training and Teaching Hospital between January 2018 and December 2021 were retrospectively reviewed. Patients with any high-risk HPV positivity who had cervical smear cytology and colposcopy directed biopsy results were included to this study. Results of HPV subtypes, cervical smear and histologic biopsy were recorded.
Results: A total of 734 patients were included to this study. The mean age of the patients was 41.9 ± 7.36 years. Hundred and sixty-five (22.5%) patients had HPV 16 alone, 35 (4.8%) had HPV 18 alone, 354 (48.2%) had other high-risk HPV subtypes alone and 180 (24.5%) had more than one high-risk HPV subtypes. Two hundred and ninety-eight (40.6%) had HPV 16 or HPV 18 either alone or in combination with other subtypes. Majority of the patients (55.3%) had normal cervical smear results followed by ASC-US (27%). Colposcopy directed biopsy results were as follows: 452 (61.6%) normal, 199 (27.1%) CIN 1, 36 (4.9%) CIN 2, 42 (5.7%) CIN 3 and 5 (0.7%) squamous cell cancer. 66.1% of the patients with HPV 16 and/or HPV 18 had normal cervical cytology results, but they had significantly more ≥CIN 2 lesions compared to other high-risk HPV subtypes (19.8% vs 5.5%, p<0.001). There wasn’t a statistical difference between having one or more than one HPV subtype in terms of severity of the lesions (p=0.474). The sensitivity and specificity of cervical smear cytology test were 55.2% and 69.2%, respectively.
Conclusion: Although patients with HPV 16 and/or HPV 18 were more likely to have normal cervical cytology results, almost 20% of them had CIN 2 + lesions. Sensitivity of cervical cytology remains low and HPV DNA test with genotyping is more reliable as a screening tool.

Anahtar Kelimeler

Human Papillomavirus DNA test, cervical smear, colposcopy, cervical cancer screening

Kaynakça

• 1. Global Cancer Observatory 2020. Available from: https://gco.iarc.fr/today/online-analysis-table?v=2020&mode=cancer&mode_population=continents&population=900&populations=900&key=asr&sex=0&cancer=39&type=0&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&group_cancer=1&include_nmsc=1&include_nmsc_other=1 (Accessed on 31.12.2021).
• 2. Burd EM. Human papillomavirus and cervical cancer. Clin Microbiol Rev. 2003;16(1):1-17.
• 3. Tracht J, Wrenn A, Eltoum IE. Primary HPV testing verification: a retrospective ad-hoc analysis of screening algorithms on women doubly tested for cytology and HPV. Diagn Cytopathol 2017;45(7):580-6.
• 4. Pileggi C, Flotta D, Bianco A, Nobile CG, Pavia M. Is HPV DNA testing specificity comparable to that of cytological testing in primary cervical cancer screening? Results of a meta-analysis of randomized controlled trials. Int J Cancer 2014;135(1):166-77.
• 5. Ronco G, Dillner J, Elfstrom KM, Tunesi S, Snijders PJ, Arbyn M, et al. Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials. Lancet 2014;383(9916):524-32.
• 6. Perkins RB, Guido RS, Castle PE, Chelmow D, Einstein MH, Garcia F, et al. 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors. J Low Genit Tract Dis. 2020;24(2):102-131.
• 7. Nayar R, Wilbur DC. The Bethesda system for reporting cervical cytology: definitions, criteria, and explanatory notes. 3rd ed. Cham:Springer, 2015.
• 8. Nygard JF, Skare GB, Thoresen SO. The cervical cancer screening programme in Norway, 1992-2000: changes in Pap smear coverage and incidence of cervical cancer. J Med Screen 2002;9(2):86-91.
• 9. Andrae B, Kemetli L, Sparén P, Silfverdal L, Strander B, Ryd W, et al. Screening-preventable cervical cancer risks: evidence from a nationwide audit in Sweden. J Natl Cancer Inst 2008;100(9):622-9.
• 10. Tsikouras P, Zervoudis S, Manav B, Tomara E, Iatrakis G, Romanidis C, et al. Cervical cancer: screening, diagnosis and staging. J BUON 2016;21(2):320-5.
• 11. Nanda K, McCrory DC, Myers ER, Bastian LA, Hasselblad V, Hickey JD, et al. Accuracy of the Papanicolaou test in screening for and follow-up of cervical cytologic abnormalities: a systematic review. Ann Intern Med 2000;132(10):810-9.
• 12. Najib FS, Hashemi M, Shiravani Z, Poordast T, Sharifi S, Askary E. Diagnostic accuracy of cervical Pap smear and colposcopy in detecting premalignant and malignant lesions of cervix. Indian J Surg Oncol 2020;11(3):453-8.
• 13. Huy NVQ, Tam LM, Tram NVQ, Thuan DC, Vinh TQ, Thanh CN, et al. The value of visual inspection with acetic acid and Pap smear in cervical cancer screening program in low resource settings - A population-based study. Gynecol Oncol Rep 2018;24:18-20.
• 14. Ozalp SS, Us T, Arslan E, Oge T, Kaşifoğlu N. HPV DNA and Pap smear test results in cases with and without cervical pathology. J Turk Ger Gynecol Assoc 2012;13(1):8-14.
• 15. Nkwabong E, Laure Bessi Badjan I, Sando Z. Pap smear accuracy for the diagnosis of cervical precancerous lesions. Trop Doct 2019;49(1):34-9.
• 16. Stoler MH, Shiffman M. Interobserver reproducibility of cervical cytologic and histologic interpretations: realistic estimates from the ASCUS-LSIL Triage Study. JAMA 2001;285(11):1500-5.
• 17. Whitlock EP, Vesco KK, Eder M, Lin JS, Senger CA, Burda BU. Liquid-based cytology and human papillomavirus testing to screen for cervical cancer: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2011;155(10):687-97.
• 18. Wright TC, Stoler MH, Behrens CM, Sharma A, Zhang G, Wright TL. Primary cervical cancer screening with human papillomavirus: end of study results from the ATHENA study using HPV as the first-line screening test. Gynecol Oncol 2015;136(2):189-97.
• 19. Paluszkiewicz A, Pruski D, Iwaniec K, Kędzia W. Comparison of the diagnostic value of cervical cytology and HPV HR DNA testing for the diagnosis of low-grade and high-grade squamous intraepithelial lesions across different age groups. Ginekol Pol 2017;88(3):141-6.
• 20. Ogilvie GS, Krajden M, van Niekerk D, Smith LW, Cook D, Ceballos K, et al. HPV for cervical cancer screening (HPV FOCAL): Complete Round 1 results of a randomized trial comparing HPV-based primary screening to liquid-based cytology for cervical cancer. Int J Cancer 2017;140(2):440-8.
• 21. Bruni L, Diaz M, Castellsague X, Ferrer E, Bosch FX, de Sanjose S. Cervical human papillomavirus prevalence in 5 continents: meta-analysis of 1 million women with normal cytological findings. J Infect Dis 2010;202(12):1789-99.
• 22. Zhang J, Cheng K, Wang Z. Prevalence and distribution of human papillomavirus genotypes in cervical intraepithelial neoplasia in China: a meta-analysis. Arch Gynecol Obstet 2020;302(6):1329-37.
• 23. de Martel C, Plummer M, Vignat J, Franceschi S. Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer 2017;141(4):664-70.