A Study on the Utility of Screening Tests in Squamous Cell Carcinoma (SCC) and High-grade Intraepithelial Lesions (HSIL) of the Cervix: Evaluation of 447 Cases with Histopathological Diagnosis
Year 2024,
, 317 - 325, 01.07.2024
Süheyla Ekemen
,
Davut Şahin
,
Sadik Toprak
,
Ebru Bilir
,
Meryem Akbaş
,
Ümit İnce
,
Serkan Erkanlı
Abstract
Introduction:
Cervical cancer is one of the most common cancers in women. Precancerous lesions of the cervix
can be detected with the combined use of smear testing and HPV (Human Papillomavirus)
testing. International guidelines have been developed to indicate at what intervals and in which
situations the tests should be performed. In this study, we examined the clinical utility of screening tests in patients with histopathologically diagnosed SCC (squamous cell carcinoma) and HSIL.
Metods:
Between January 2022 and June 2023, 447 patients aged 19-73 years (mean 37) with cervical
biopsy results of SCC and HSIL were evaluated for the use of diagnostic tests (PAP smear and
HPV test).
Results:
PAP smears were performed in 98.2% and HPV tests in 39.1% of all cases before histopathologic
diagnosis. The most frequently detected high-risk HPV (hrHPV) was type 16. HPV testing
significantly decreased with age. HPV testing was not performed in 74.2% of patients aged 51-
60 years and 80.9% of patients over 60 years.
Conclusion:
These cases the clinical utility and pathologic evaluation of the PAP smear were optimal. However, HPV testing practice was decreasing, especially with age. Cytologic evaluation may be misleading due to age-related hormonal withdrawal, difficulty in obtaining adequate smears, and atrophic changes. Our recommendation is to use HPV testing in all age groups, but especially in the population over 50 years of age, where cytologic difficulties may occur, HPV testing should be performed optimally until 65 years of age.
Thanks
S.E. is a Clinical Fellow of the Takeda Science Foundation and greatly acknowledges educational support from them.
References
- 1. Perkins RB, Wentzensen N, Guido RS, Schiffman M. Cervical Cancer Screening. JAMA. 2023;330(6):547. doi:10.1001/jama.2023.13174
- 2. Kjær SK, Munk C, Junge J, Iftner T. Carcinogenic HPV prevalence and age-specific type distribution in 40,382 women with normal cervical cytology, ASCUS/LSIL, HSIL, or cervical cancer: What is the potential for prevention? Cancer Causes and Control. 2014;25(2). doi:10.1007/s10552-013-0320-z
- 3. Quinn BA, Deng X, Colton A, Bandyopadhyay D, Carter JS, Fields EC. Increasing age predicts poor cervical cancer prognosis with subsequent effect on treatment and overall survival. Brachytherapy. 2019;18(1). doi:10.1016/j.brachy.2018.08.016
- 4. Wentzensen N, Clarke MA. Cervical cancer screening - Past, present, and future. Cancer Epidemiology Biomarkers and Prevention. 2021;30(3). doi:10.1158/1055-9965.EPI-20-1628
- 5. Bamanikar S, Baravkar D, Chandanwale S, Dharwadkar A, Paranjape S. Study of cervical cytology and its correlation with clinical and histopathological findings. Clin Cancer Investig J. 2016;5(5). doi:10.4103/2278-0513.197869
- 6. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6). doi:10.3322/caac.21492
- 7. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3). doi:10.3322/caac.21660
- 8. Guan P, Howell-Jones R, Li N, et al. Human papillomavirus types in 115,789 HPV-positive women: A meta-analysis from cervical infection to cancer. Int J Cancer. 2012;131(10). doi:10.1002/ijc.27485
- 9. Aggarwal P. HPV Infection: Pathogenesis and Detection. In: Preventive Oncology for the Gynecologist. ; 2019. doi:10.1007/978-981-13-3438-2_9
10. Bhatla N, Singhal S. Primary HPV screening for cervical cancer. Best Pract Res Clin Obstet Gynaecol. 2020;65. doi:10.1016/j.bpobgyn.2020.02.008
- 11. Yousefi Z, Aria H, Ghaedrahmati F, et al. An Update on Human Papilloma Virus Vaccines: History, Types, Protection, and Efficacy. Front Immunol. 2022;12. doi:10.3389/fimmu.2021.805695
- 12. Gutiérrez J, García-Villa E, Ocadiz-Delgado R, et al. Human papillomavirus type 16 E7 oncoprotein upregulates the retinoic acid receptor-beta expression in cervical cancer cell lines and K14E7 transgenic mice. Mol Cell Biochem. 2015;408(1-2). doi:10.1007/s11010-015-2504-1
- 13. Allahqoli L, Laganà AS, Mazidimoradi A, et al. Diagnosis of Cervical Cancer and Pre-Cancerous Lesions by Artificial Intelligence: A Systematic Review. Diagnostics. 2022;12(11). doi:10.3390/diagnostics12112771
- 14. Canfell K. Towards the global elimination of cervical cancer. Papillomavirus Research. 2019;8. doi:10.1016/j.pvr.2019.100170
- 15. Kim SI, Kim SJ, Suh DH, Kim K, No JH, Kim YB. Pathologic discrepancies between colposcopy-directed biopsy and loop electrosurgical excision procedure of the uterine cervix in women with cytologic high-grade squamous intraepithelial lesions. J Gynecol Oncol. 2020;31(2). doi:10.3802/jgo.2020.31.e13
- 16. Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda System: Terminology for reporting results of cervical cytology. J Am Med Assoc. 2002;287(16). doi:10.1001/jama.287.16.2114
- 17. Nayar R, Wilbur DC. The bethesda system for reporting cervical cytology: A historical perspective. Acta Cytol. 2017;61(4-5). doi:10.1159/000477556
- 18. Massad LS, Einstein MH, Huh WK, et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstetrics and Gynecology. 2013;121(4). doi:10.1097/AOG.0b013e3182883a34
- 19. Perkins RB, Guido RS, Castle PE, et al. Erratum: 2019 ASCCP risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors (Journal of Lower Genital Tract Disease (2020) 24 (102-131) DOI: 10.1097/LGT.0000000000000525). J Low Genit Tract Dis. 2021;25(4). doi:10.1097/LGT.0000000000000628
- 20. Schulmeyer CE, Stübs F, Gass P, et al. Correlation between referral cytology and in-house colposcopy-guided cytology for detecting early cervical neoplasia. Arch Gynecol Obstet. 2020;301(1). doi:10.1007/s00404-019-05389-1
- 21. Anschau F, Guimarães Gonçalves MA. Discordance between cytology and biopsy histology of the cervix: What to consider and what to do. Acta Cytol. 2011;55(2). doi:10.1159/000320911
- 22. David J, Joshi V, Jebin Aaron D, Baghel P. A Comparative Analysis of Visual Inspection With Acetic Acid, Cervical Cytology, and Histopathology in the Screening and Early Detection of Premalignant and Malignant Lesions of the Cervix. Cureus. Published online 2022. doi:10.7759/cureus.29762
- 23. Ekemen S, Comunoglu C, Kayhan CK, et al. Endometrial Staining of CD56 (Uterine Natural Killer), BCL-6, and CD138 (Plasma Cells) Improve Diagnosis and Clinical Pregnancy Outcomes in Unexplained Infertility and Recurrent IVF Failures: Standardization of Diagnosis with Digital Pathology. Diagnostics. 2023;13(9). doi:10.3390/diagnostics13091557
- 24. Davey DD, Souers RJ, Goodrich K, Mody DR, Tabbara SO, Booth CN. Bethesda 2014 implementation and human papillomavirus primary screening practices of laboratories participating in the College of American Pathologists PAP education program. Arch Pathol Lab Med. 2019;143(10). doi:10.5858/arpa.2018-0603-CP
- 25. Sahin D. Effects of an Additional Liquid Based Cytology Prepate on Cytological Diagnosis in High Risk HPV Positive, PAP Test Negative Cases. SiSli Etfal Hastanesi Tip Bulteni / The Medical Bulletin of Sisli Hospital. Published online 2019. doi:10.14744/semb.2019.23434
- 26. Cox T, Cuzick J. HPV DNA testing in cervical cancer screening: From evidence to policies. Gynecol Oncol. 2006;103(1). doi:10.1016/j.ygyno.2006.07.030
- 27. Crothers BA, Booth CN, Darragh TM, et al. False-Positive papanicolaou (pap) test rates in the college of american pathologists pap education and pap proficiency test programs : Evaluation of False-Positive responses of high-grade squamous intraepithelial lesion or cancer to a negative reference diagnosis. Arch Pathol Lab Med. 2014;138(5). doi:10.5858/arpa.2013-0083-CP
Year 2024,
, 317 - 325, 01.07.2024
Süheyla Ekemen
,
Davut Şahin
,
Sadik Toprak
,
Ebru Bilir
,
Meryem Akbaş
,
Ümit İnce
,
Serkan Erkanlı
References
- 1. Perkins RB, Wentzensen N, Guido RS, Schiffman M. Cervical Cancer Screening. JAMA. 2023;330(6):547. doi:10.1001/jama.2023.13174
- 2. Kjær SK, Munk C, Junge J, Iftner T. Carcinogenic HPV prevalence and age-specific type distribution in 40,382 women with normal cervical cytology, ASCUS/LSIL, HSIL, or cervical cancer: What is the potential for prevention? Cancer Causes and Control. 2014;25(2). doi:10.1007/s10552-013-0320-z
- 3. Quinn BA, Deng X, Colton A, Bandyopadhyay D, Carter JS, Fields EC. Increasing age predicts poor cervical cancer prognosis with subsequent effect on treatment and overall survival. Brachytherapy. 2019;18(1). doi:10.1016/j.brachy.2018.08.016
- 4. Wentzensen N, Clarke MA. Cervical cancer screening - Past, present, and future. Cancer Epidemiology Biomarkers and Prevention. 2021;30(3). doi:10.1158/1055-9965.EPI-20-1628
- 5. Bamanikar S, Baravkar D, Chandanwale S, Dharwadkar A, Paranjape S. Study of cervical cytology and its correlation with clinical and histopathological findings. Clin Cancer Investig J. 2016;5(5). doi:10.4103/2278-0513.197869
- 6. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6). doi:10.3322/caac.21492
- 7. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3). doi:10.3322/caac.21660
- 8. Guan P, Howell-Jones R, Li N, et al. Human papillomavirus types in 115,789 HPV-positive women: A meta-analysis from cervical infection to cancer. Int J Cancer. 2012;131(10). doi:10.1002/ijc.27485
- 9. Aggarwal P. HPV Infection: Pathogenesis and Detection. In: Preventive Oncology for the Gynecologist. ; 2019. doi:10.1007/978-981-13-3438-2_9
10. Bhatla N, Singhal S. Primary HPV screening for cervical cancer. Best Pract Res Clin Obstet Gynaecol. 2020;65. doi:10.1016/j.bpobgyn.2020.02.008
- 11. Yousefi Z, Aria H, Ghaedrahmati F, et al. An Update on Human Papilloma Virus Vaccines: History, Types, Protection, and Efficacy. Front Immunol. 2022;12. doi:10.3389/fimmu.2021.805695
- 12. Gutiérrez J, García-Villa E, Ocadiz-Delgado R, et al. Human papillomavirus type 16 E7 oncoprotein upregulates the retinoic acid receptor-beta expression in cervical cancer cell lines and K14E7 transgenic mice. Mol Cell Biochem. 2015;408(1-2). doi:10.1007/s11010-015-2504-1
- 13. Allahqoli L, Laganà AS, Mazidimoradi A, et al. Diagnosis of Cervical Cancer and Pre-Cancerous Lesions by Artificial Intelligence: A Systematic Review. Diagnostics. 2022;12(11). doi:10.3390/diagnostics12112771
- 14. Canfell K. Towards the global elimination of cervical cancer. Papillomavirus Research. 2019;8. doi:10.1016/j.pvr.2019.100170
- 15. Kim SI, Kim SJ, Suh DH, Kim K, No JH, Kim YB. Pathologic discrepancies between colposcopy-directed biopsy and loop electrosurgical excision procedure of the uterine cervix in women with cytologic high-grade squamous intraepithelial lesions. J Gynecol Oncol. 2020;31(2). doi:10.3802/jgo.2020.31.e13
- 16. Solomon D, Davey D, Kurman R, et al. The 2001 Bethesda System: Terminology for reporting results of cervical cytology. J Am Med Assoc. 2002;287(16). doi:10.1001/jama.287.16.2114
- 17. Nayar R, Wilbur DC. The bethesda system for reporting cervical cytology: A historical perspective. Acta Cytol. 2017;61(4-5). doi:10.1159/000477556
- 18. Massad LS, Einstein MH, Huh WK, et al. 2012 updated consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Obstetrics and Gynecology. 2013;121(4). doi:10.1097/AOG.0b013e3182883a34
- 19. Perkins RB, Guido RS, Castle PE, et al. Erratum: 2019 ASCCP risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors (Journal of Lower Genital Tract Disease (2020) 24 (102-131) DOI: 10.1097/LGT.0000000000000525). J Low Genit Tract Dis. 2021;25(4). doi:10.1097/LGT.0000000000000628
- 20. Schulmeyer CE, Stübs F, Gass P, et al. Correlation between referral cytology and in-house colposcopy-guided cytology for detecting early cervical neoplasia. Arch Gynecol Obstet. 2020;301(1). doi:10.1007/s00404-019-05389-1
- 21. Anschau F, Guimarães Gonçalves MA. Discordance between cytology and biopsy histology of the cervix: What to consider and what to do. Acta Cytol. 2011;55(2). doi:10.1159/000320911
- 22. David J, Joshi V, Jebin Aaron D, Baghel P. A Comparative Analysis of Visual Inspection With Acetic Acid, Cervical Cytology, and Histopathology in the Screening and Early Detection of Premalignant and Malignant Lesions of the Cervix. Cureus. Published online 2022. doi:10.7759/cureus.29762
- 23. Ekemen S, Comunoglu C, Kayhan CK, et al. Endometrial Staining of CD56 (Uterine Natural Killer), BCL-6, and CD138 (Plasma Cells) Improve Diagnosis and Clinical Pregnancy Outcomes in Unexplained Infertility and Recurrent IVF Failures: Standardization of Diagnosis with Digital Pathology. Diagnostics. 2023;13(9). doi:10.3390/diagnostics13091557
- 24. Davey DD, Souers RJ, Goodrich K, Mody DR, Tabbara SO, Booth CN. Bethesda 2014 implementation and human papillomavirus primary screening practices of laboratories participating in the College of American Pathologists PAP education program. Arch Pathol Lab Med. 2019;143(10). doi:10.5858/arpa.2018-0603-CP
- 25. Sahin D. Effects of an Additional Liquid Based Cytology Prepate on Cytological Diagnosis in High Risk HPV Positive, PAP Test Negative Cases. SiSli Etfal Hastanesi Tip Bulteni / The Medical Bulletin of Sisli Hospital. Published online 2019. doi:10.14744/semb.2019.23434
- 26. Cox T, Cuzick J. HPV DNA testing in cervical cancer screening: From evidence to policies. Gynecol Oncol. 2006;103(1). doi:10.1016/j.ygyno.2006.07.030
- 27. Crothers BA, Booth CN, Darragh TM, et al. False-Positive papanicolaou (pap) test rates in the college of american pathologists pap education and pap proficiency test programs : Evaluation of False-Positive responses of high-grade squamous intraepithelial lesion or cancer to a negative reference diagnosis. Arch Pathol Lab Med. 2014;138(5). doi:10.5858/arpa.2013-0083-CP