Document Type : Original Article
Authors
1 Ph.D., Professor, National Iranian Association of Gynecologists and obstetricians (Naigo), Tehran, Iran
2 Ph.D., Obstetrics and Gynecology ward, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
3 Ph.D., Assistant Professor, Department of Molecular Diagnosis, Armin Pathobiology Laboratory, Tehran, Iran
4 Ph.D., Professor, Pathology ward, Imam Khomeini Hospital, Tehan University of Medical Sciences, Tehran, Iran
Abstract
Introduction: Cytology testing has been successful in reducing the incidence of cervical cancer and mortality. Molecular testing like HPV typing and Aptima test can improve screening effectiveness. We compared the diagnostic value of cytology testing, High-risk (HR) HPV DNA typing, and APTIMA tests based on the results of the cervical biopsy in the diagnosis of cervical cancer and neoplasia in patients referred to Imam Khomeini Hospital.
Methods: One hundred fifty women between 21 and 56 years old who referred to having clinical symptoms or conducting screening tests enrolled in the study. Sensitivity, specificity, positive and negative predictive values, and accuracy for cervical involvement were calculated for cytology, High-risk HPV testing, and APTIMA tests separately.
Results: The most abundant genotype found was HPV 16. cytology testing had a sensitivity of 59% for CIN 2+ and a specificity of 61% for CIN 2+. For CIN I, the sensitivity and specificity of cytology testing were higher (63% and 71%, respectively). High-risk HPV typing had the highest sensitivity (76%) for CIN 2+, but its specificity was low (66%). Its sensitivity was 51% for CIN I with a specificity of 74%. APTIMA tests had a sensitivity of 53.7% and a specificity of 87.5% for CIN2 +, which was less sensitive to High-risk HPV typing but was more specific. The APTIMA test sensitivity for CIN I was very low (22.2%), but its specificity was high (87.5%).
Conclusion: High-risk HPV typing showed the highest sensitivity (75.9%) and APTIMA tests had the highest specificity (87.5%) in predicting CIN 2+.
Keywords
- Burchell AN, Winer RL, de Sanjose S, Franco EL. Chapter 6: Epidemiology and transmission dynamics of genital HPV infection. Vaccine 2006 Aug 31;24 Suppl 3:S3/52-61.
- Forman D, de Martel C, Lacey CJ, Soerjomataram I, Lortet-Tieulent J, Bruni L, et al. Global burden of human papillomavirus and related diseases. Vaccine. 2012;30 Suppl 5:F12-23.
- Bell RJ, Fradkin P, Parathithasan N, Robinson PJ, Schwarz M, Davis SR. Pregnancy-associated breast cancer and pregnancy following treatment for breast cancer, in a cohort of women from Victoria, Australia, with a first diagnosis of invasive breast cancer. Breast. 2013;22(5):980-5.
- Correa Mda S, Silveira DS, Siqueira FV, Facchini LA, Piccini RX, Thume E, et al. [Pap test coverage and adequacy in the South and Northeast of Brazil]. Cad Saude Publica. 2012;28(12):2257-66.
- Geldenhuys L, Murray ML. Sensitivity and specificity of the Pap smear for glandular lesions of the cervix and endometrium. Acta Cytol 2007;
51(1):47-50. - Chen YC, Liu HY, Li CY, Lee NY, Ko WC, Chou CY, et al. Low Papanicolaou smear screening rate of women with HIV infection: a nationwide population-based study in Taiwan, 2000-2010. J Womens Health (Larchmt). 2013;22(12):1016-22.
- Bobdey S, Sathwara J, Jain A, Balasubramaniam G. Burdenof cervical cancer and role of screening in India. Indian journal of medical and paediatric oncology : official journal of Indian Society of Medical & Paediatric Oncology. 2016;37(4):278-85.
- Manos MM, Kinney WK, Hurley LB, Sherman ME, Shieh-Ngai J, Kurman RJ, et al. Identifying women with cervical neoplasia: using human papillomavirus DNA testing for equivocal Papanicolaou results. Jama. 1999;281(17):1605-10.
- Cuzick J, Sasieni P, Davies P, Adams J, Normand C, Frater A, et al. A systematic review ofthe role of human papillomavirus testing within a cervical screening programme. Health Technol Assess. 1999;3(14):i-iv, 1-196.
- Saslow D, Solomon D, Lawson HW, Killackey M, Kulasingam SL, Cain J, 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. CA Cancer J Clin. 2012;62(3):147-72. - Liang H, Griffith CC, Ma L, Ling B, Feng D, Li Z, et al. The sensitivity of Pap cytology and HPV testing to detect incident cervical cancer: prior testing results in 178 patients with invasive cervical cancer at a large general hospital in China. Journal of the American Society of Cytopathology. 2016;5(2):64-70.
- Adamopoulou M, Kalkani E, Charvalos E, Avgoustidis D, Haidopoulos D, Yapijakis C. Comparison of cytology, colposcopy, HPV typing and biomarker analysis in cervical neoplasia. Anticancer Res. 2009;29(8):3401-9.
- Monsonego J, Pinto J, Semaille C, Beumont M, Dachez R, Zerat L, Bianchi A and Franco E. Human papillomavirus testing improves the accuracy of colposcopy in detection of cervical intrapithelial neoplasia. Int J Gynecol Cancer 16: 591-598, 2006.
- Miller AB, Sankaranarayanan R, Bosch FX, Sepulveda C. Can screening for cervical cancer be improved, especially in developing countries? Int J Cancer. 2003;107(3):337-40.
- 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 Oncol. 2009;10(7):672-82. - Arbyn M, Sasieni P, Meijer CJ, Clavel C, Koliopoulos G, Dillner J. Chapter 9: Clinical applications of HPV testing: a summary of meta-analyses. Vaccine. 2006;24 Suppl 3:S3/78-89.
- Jastania R, Geddie WR, Chapman W, Boerner S. Characteristics of apparently false-negative digene hybrid capture 2 high-risk HPV DNA testing. Am J Clin Pathol. 2006;125(2):223-8.
- Pirog EC, Lloveras B, Molijn A, Tous S, Guimera N, Alejo M, et al. HPV prevalence and genotypes in different histological subtypes of cervical adenocarcinoma, a worldwide analysis of 760 cases. Mod Pathol. 2014;27(12):1559-67.
- de Sanjose S, Quint WG, Alemany L, Geraets DT, Klaustermeier JE, Lloveras B, et al. Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study. Lancet Oncol. 2010;11(11):1048-56.
- Bigras G, de Marval F. The probability for a Pap test to be abnormal is directly proportional to HPV viral load: results from a Swiss study comparing HPV
testing and liquid-based cytology to detect cervical cancer precursors in 13,842 women. Br J Cancer. 2005;93(5):575-81. - Renshaw AA, Elsheikh TM. Predicting screening sensitivity from workload in gynecologic cytology: a review. Diagn Cytopathol. 2011;39(11):832-6.
- Castle PE, Eaton B, Reid J, Getman D, Dockter J. Comparison of human papillomavirus detection by Aptima HPV and cobas HPV tests in a population ofwomen referred for colposcopy following detection of atypical squamous cells of undetermined significance by Pap cytology. Journal of Clinical Microbiology. 2015;53(4):1277-81.
- Szarewski A, Mesher D, Cadman L, Austin J, Ashdown-Barr L, Ho L, et al. Comparison of seven tests for high-grade cervical intraepithelial neoplasia in women with abnormal smears: the Predictors 2 study. Journal of clinical microbiology. 2012;50(6):1867-73.
- Ovestad IT, Vennestrom U, Andersen L, Gudlaugsson E, Munk AC, Malpica A, et al. Comparison of different commercial methods for HPV detection in follow-up cytology after ASCUS/LSIL, prediction of CIN2-3 in follow up biopsies and spontaneous regression of CIN2-3. Gynecol Oncol. 2011;123(2):278-83.
- Cuzick J, Cadman L, Mesher D, Austin J, Ashdown-Barr L, Ho L, et al. Comparing the performance of six human papillomavirus tests in a screening population. Br J Cancer. 2013;108(4):908-13.
- Dockter J, Schroder A, Hill C, Guzenski L, Monsonego J, Giachetti C. Clinical performance of the APTIMA HPV Assay for the detection of high-risk HPV and high-grade cervical lesions. J Clin Virol. 2009;45 Suppl 1:S55-61.
- Cox JT. The clinician's view: role of human papillomavirus testing in the American Society for Colposcopy and Cervical Pathology Guidelines for the management of abnormal cervical cytology and cervical cancer precursors. Arch Pathol Lab Med. 2003;127(8):950-8