Research Article
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SMILE, Servikal İntraepitelyal Neoplazi 3 ve Adenokarsinoma in situ Hastalarının Klinikopatolojik Değerlendirilmesi

Year 2025, Volume: 16 Issue: 3, 625 - 633, 30.09.2025
https://doi.org/10.18663/tjcl.1788113

Abstract

Amaç: SMILE, CIN3 ve AIS tanılı hastalarda servikal biyopsi sonuçlarının konizasyon/histerektomi sonrası kesin patolojik tanılarla uyumunu ve klinik özelliklerdeki farklılıkları karşılaştırmak.
Yöntemler: Tek merkezli retrospektif bir çalışma kapsamında SMILE (n=8), CIN3 (n=16) veya AIS (n=14) tanısı alarak cerrahi tedavi uygulanmış hastaların klinikopatolojik verileri incelenmiştir. Hastaların HPV genotip sonuçları, sitoloji (Pap smear) bulguları, uygulanan cerrahi işlemler ve cerrahi örneklerin patoloji sonuçları retrospektif olarak kayıt edildi.
Bulgular: HPV yüksek riskli genotip dağılımı ve sitolojik tanılar gruplar arasında benzer bulundu (p>0.05). AIS tanılı hastalarda ilk tedavide veya yeniden cerrahi sonrası histerektomi uygulanma oranı diğer gruplara kıyasla daha yüksekti. Biyopsi ön tanısı ile cerrahi eksizyon sonrası patoloji tanısının uyumu lezyon tiplerine göre anlamlı farklılık gösterdi (p<0.001). İkinci bir cerrahi girişim gereksinimi AIS ve CIN3 olgularında, SMILE olgularına göre anlamlı olarak daha sık izlendi (p=0.011). Bununla birlikte, tekrar cerrahi yapılan hastalarda elde edilen nihai patoloji sonuçları gruplar arasında belirgin bir fark göstermedi.
Sonuç: SMILE, CIN3 ve AIS olgularında HPV tipleri ve sitoloji sonuçları benzer olsa da biyopsi ile cerrahi patoloji uyumu özellikle glandüler lezyonlarda (AIS ve SMILE) değişkenlik gösterebilir. AIS ve CIN3 olgularında cerrahi sınır pozitifliği veya yetersiz tedavi nedeniyle ikinci bir cerrahi girişime ihtiyaç duyma oranının yüksek oluşu, bu lezyonlarda tedavi planlanırken dikkatli olunması gerektiğini göstermektedir.

References

  • Mishra GA, Pimple SA, and Shastri SS. An overview of prevention and early detection of cervical cancers. Indian J Med Paediatr Oncol. 2011;32(3):125-32.
  • Smedts F, Ramaekers FC, and Hopman AH. The two faces of cervical adenocarcinoma in situ. Int J Gynecol Pathol. 2010;29(4):378-85.
  • Gupta S, Nagtode N, Chandra V, and Gomase K. From Diagnosis to Treatment: Exploring the Latest Management Trends in Cervical Intraepithelial Neoplasia. Cureus. 2023;15(12):e50291.
  • Martin‐Hirsch PP, Paraskevaidis E, Bryant A, Dickinson HO, Cochrane Gynaecological No, and Group OC. Surgery for cervical intraepithelial neoplasia. Cochrane database of systematic reviews. 1996;2014(2)
  • Ramirez SI and Lutzkanin A. Management of cervical dysplasia using office loop electrosurgical excision procedure. Primary Care: Clinics in Office Practice. 2021;48(4):583-95.
  • Lili E, Chatzistamatiou K, Kalpaktsidou-Vakiani A, Moysiadis T, and Agorastos T. Low recurrence rate of high-grade cervical intraepithelial neoplasia after successful excision and routine colposcopy during follow-up. Medicine. 2018;97(4):e9719.
  • Wu Q, Jiang Y, Ding J, Xia L, and Xu H. Clinical predictors of residual disease in hysterectomy following a loop electrosurgical excision procedure for cervical intraepithelial neoplasia grade 3. BMC Pregnancy and Childbirth. 2022;22(1):971.
  • Schaafsma M, Schuurman TN, Bekkers RLM, et al. The risk for residual AIS/CIN3+ after the first conservative surgical procedure for cervical adenocarcinoma in situ - A Dutch retrospective cohort study. Gynecol Oncol. 2025;200:44-50.
  • Delli Carpini G, Cicoli C, Bernardi M, Di Giuseppe J, Giannella L, and Ciavattini A. Clinical Outcomes of Cervical Adenocarcinoma In Situ According to Conservative or Demolitive Treatment: A Systematic Review and Meta-Analysis. Cancers (Basel). 2025;17(11)
  • Liu J, Wang Y, Wan X, et al. Comparison of the safety between cervical conization and hysterectomy for patients with cervical adenocarcinoma in situ. Journal of Gynecologic Oncology. 2022;34(1):e8.
  • Stuebs FA, Dietl AK, Behrens A, et al. Concordance Rate of Colposcopy in Detecting Cervical Intraepithelial Lesions. Diagnostics (Basel). 2022;12(10)
  • Veridiano NP, Delke I, and Tancer ML. Accuracy of colposcopically directed biopsy in patients with cervical neoplasia. Obstet Gynecol. 1981;58(2):185-7.
  • Teoh D, Musa F, Salani R, Huh W, and Jimenez E. Diagnosis and Management of Adenocarcinoma in Situ: A Society of Gynecologic Oncology Evidence-Based Review and Recommendations. Obstet Gynecol. 2020;135(4):869-78.
  • Clarke MA, Befano B, Wentzensen N, et al. Associations of obesity with post-treatment risks of cervical precancer and cancer. Am J Obstet Gynecol. 2025;233(1):40 e1-40 e16.
  • Park IS, Kim SI, Han Y, et al. Risk of female-specific cancers according to obesity and menopausal status in 2*7 million Korean women: Similar trends between Korean and Western women. Lancet Reg Health West Pac. 2021;11:100146.
  • Strojan Flezar M, Nedelko N, Poljak M, Ostrbenk Valencak A, and Gutnik H. Stratified Mucin-Producing Intraepithelial Lesion (SMILE) of the Uterine Cervix: High-Risk HPV Genotype Predominance and p40 Immunophenotype. Cells. 2021;10(8)
  • Huang X, Zhao Q, Yang P, et al. Metabolic Syndrome and Risk of Cervical Human Papillomavirus Incident and Persistent Infection. Medicine (Baltimore). 2016;95(9):e2905.
  • Shen T, Zhao J, Li W, et al. Hypertension and hyperglycaemia are positively correlated with local invasion of early cervical cancer. Front Endocrinol (Lausanne). 2023;14:1280060.
  • Luo Q, Zeng X, Luo H, et al. Epidemiologic characteristics of high-risk HPV and the correlation between multiple infections and cervical lesions. BMC Infect Dis. 2023;23(1):667.
  • Cleveland AA, Gargano JW, Park IU, et al. Cervical adenocarcinoma in situ: Human papillomavirus types and incidence trends in five states, 2008-2015. Int J Cancer. 2020;146(3):810-18.
  • Braaten KP and Laufer MR. Human Papillomavirus (HPV), HPV-Related Disease, and the HPV Vaccine. Rev Obstet Gynecol. 2008;1(1):2-10.
  • Miller RA, Mody DR, Tams KC, and Thrall MJ. Glandular Lesions of the Cervix in Clinical Practice: A Cytology, Histology, and Human Papillomavirus Correlation Study From 2 Institutions. Arch Pathol Lab Med. 2015;139(11):1431-6.
  • Lashmanova N, Braun A, Cheng L, Gattuso P, and Yan L. Endocervical adenocarcinoma in situ-from Papanicolaou test to hysterectomy: a series of 74 cases. J Am Soc Cytopathol. 2022;11(1):13-20.
  • Bruno MT, Valenti G, Cassaro N, et al. The Coexistence of Cervical Intraepithelial Neoplasia (CIN3) and Adenocarcinoma In Situ (AIS) in LEEP Excisions Performed for CIN3. Cancers (Basel). 2024;16(5)
  • Schwock J, Ko HM, Dube V, et al. Stratified Mucin-Producing Intraepithelial Lesion of the Cervix: Subtle Features Not to Be Missed. Acta Cytol. 2016;60(3):225-31.
  • Yang EJ, Kim NR, Choi JY, Kim WY, and Lee SJ. Loop electrosurgical excision procedure combined with cold coagulation for cervical intraepithelial neoplasia and adenocarcinoma in-situ: a feasible treatment with a low risk of residual/recurrent disease. Infect Agent Cancer. 2020;15:58.
  • Bruno MT, Cavallaro AG, Fiore M, et al. Endocervical Curettage and Extended HPV Genotyping as Predictors of Residual Disease After Hysterectomy in Postmenopausal Women Previously Treated with LEEP for CIN3: A Multivariate Analysis. Cancers (Basel). 2025;17(13)
  • Akgor U, Ozgul N, Gunes AC, Turkyilmaz M, and Gultekin M. Evaluation of Endocervical Curettage in Colposcopy in the Turkish Cervical Cancer Screening Program. J Clin Med. 2024;13(15)
  • Inal HA, Han O, Ozturk Inal Z, Eren Karanis MI, and Kucukosmanoglu I. Evaluation of concordance between loop electrosurgical excisional procedure and cervical colposcopic biopsy results. J Turk Ger Gynecol Assoc. 2024;25(1):13-17.

Clinicopathological Evaluation of Patients with SMILE, Cervical Intraepithelial Neoplasia 3, and Adenocarcinoma in Situ

Year 2025, Volume: 16 Issue: 3, 625 - 633, 30.09.2025
https://doi.org/10.18663/tjcl.1788113

Abstract

Aim: To compare cervical biopsy diagnoses with final surgical pathology results among patients with SMILE, CIN3, and AIS, and to evaluate differences in clinical-pathological features between these lesions.
Methods: We performed a retrospective single-center analysis of patients diagnosed with SMILE (n=8), CIN3 (n=16), or AIS (n=14) who underwent surgical treatment. Clinical variables, high-risk HPV genotypes, cervical cytology findings, treatment modality, and pathological outcomes of surgical specimens were reviewed.
Results: The distribution of HPV high-risk genotypes and cytologic diagnoses were similar between the groups (p>0.05). The rate of hysterectomy performed during initial treatment or after reoperation was higher in patients with AIS compared to the other groups. The concordance between the preliminary biopsy diagnosis and the pathological diagnosis after surgical excision differed significantly across lesion types (p<0.001). The need for a second surgical intervention was significantly more common in AIS and CIN3 cases than in SMILE cases (p=0.011). However, the final pathological results obtained in patients who underwent reoperation did not show a significant difference between the groups.
Conclusion: Although the distribution of oncogenic HPV types and cytology findings were similar in SMILE, CIN3, and AIS, the agreement between biopsy and definitive surgical pathology was significantly different, highlighting diagnostic and management challenges especially for glandular lesions. The need for repeat surgical treatment was notably higher in AIS and CIN3 cases, underscoring the importance of thorough initial treatment and follow-up in these high-grade lesions.

References

  • Mishra GA, Pimple SA, and Shastri SS. An overview of prevention and early detection of cervical cancers. Indian J Med Paediatr Oncol. 2011;32(3):125-32.
  • Smedts F, Ramaekers FC, and Hopman AH. The two faces of cervical adenocarcinoma in situ. Int J Gynecol Pathol. 2010;29(4):378-85.
  • Gupta S, Nagtode N, Chandra V, and Gomase K. From Diagnosis to Treatment: Exploring the Latest Management Trends in Cervical Intraepithelial Neoplasia. Cureus. 2023;15(12):e50291.
  • Martin‐Hirsch PP, Paraskevaidis E, Bryant A, Dickinson HO, Cochrane Gynaecological No, and Group OC. Surgery for cervical intraepithelial neoplasia. Cochrane database of systematic reviews. 1996;2014(2)
  • Ramirez SI and Lutzkanin A. Management of cervical dysplasia using office loop electrosurgical excision procedure. Primary Care: Clinics in Office Practice. 2021;48(4):583-95.
  • Lili E, Chatzistamatiou K, Kalpaktsidou-Vakiani A, Moysiadis T, and Agorastos T. Low recurrence rate of high-grade cervical intraepithelial neoplasia after successful excision and routine colposcopy during follow-up. Medicine. 2018;97(4):e9719.
  • Wu Q, Jiang Y, Ding J, Xia L, and Xu H. Clinical predictors of residual disease in hysterectomy following a loop electrosurgical excision procedure for cervical intraepithelial neoplasia grade 3. BMC Pregnancy and Childbirth. 2022;22(1):971.
  • Schaafsma M, Schuurman TN, Bekkers RLM, et al. The risk for residual AIS/CIN3+ after the first conservative surgical procedure for cervical adenocarcinoma in situ - A Dutch retrospective cohort study. Gynecol Oncol. 2025;200:44-50.
  • Delli Carpini G, Cicoli C, Bernardi M, Di Giuseppe J, Giannella L, and Ciavattini A. Clinical Outcomes of Cervical Adenocarcinoma In Situ According to Conservative or Demolitive Treatment: A Systematic Review and Meta-Analysis. Cancers (Basel). 2025;17(11)
  • Liu J, Wang Y, Wan X, et al. Comparison of the safety between cervical conization and hysterectomy for patients with cervical adenocarcinoma in situ. Journal of Gynecologic Oncology. 2022;34(1):e8.
  • Stuebs FA, Dietl AK, Behrens A, et al. Concordance Rate of Colposcopy in Detecting Cervical Intraepithelial Lesions. Diagnostics (Basel). 2022;12(10)
  • Veridiano NP, Delke I, and Tancer ML. Accuracy of colposcopically directed biopsy in patients with cervical neoplasia. Obstet Gynecol. 1981;58(2):185-7.
  • Teoh D, Musa F, Salani R, Huh W, and Jimenez E. Diagnosis and Management of Adenocarcinoma in Situ: A Society of Gynecologic Oncology Evidence-Based Review and Recommendations. Obstet Gynecol. 2020;135(4):869-78.
  • Clarke MA, Befano B, Wentzensen N, et al. Associations of obesity with post-treatment risks of cervical precancer and cancer. Am J Obstet Gynecol. 2025;233(1):40 e1-40 e16.
  • Park IS, Kim SI, Han Y, et al. Risk of female-specific cancers according to obesity and menopausal status in 2*7 million Korean women: Similar trends between Korean and Western women. Lancet Reg Health West Pac. 2021;11:100146.
  • Strojan Flezar M, Nedelko N, Poljak M, Ostrbenk Valencak A, and Gutnik H. Stratified Mucin-Producing Intraepithelial Lesion (SMILE) of the Uterine Cervix: High-Risk HPV Genotype Predominance and p40 Immunophenotype. Cells. 2021;10(8)
  • Huang X, Zhao Q, Yang P, et al. Metabolic Syndrome and Risk of Cervical Human Papillomavirus Incident and Persistent Infection. Medicine (Baltimore). 2016;95(9):e2905.
  • Shen T, Zhao J, Li W, et al. Hypertension and hyperglycaemia are positively correlated with local invasion of early cervical cancer. Front Endocrinol (Lausanne). 2023;14:1280060.
  • Luo Q, Zeng X, Luo H, et al. Epidemiologic characteristics of high-risk HPV and the correlation between multiple infections and cervical lesions. BMC Infect Dis. 2023;23(1):667.
  • Cleveland AA, Gargano JW, Park IU, et al. Cervical adenocarcinoma in situ: Human papillomavirus types and incidence trends in five states, 2008-2015. Int J Cancer. 2020;146(3):810-18.
  • Braaten KP and Laufer MR. Human Papillomavirus (HPV), HPV-Related Disease, and the HPV Vaccine. Rev Obstet Gynecol. 2008;1(1):2-10.
  • Miller RA, Mody DR, Tams KC, and Thrall MJ. Glandular Lesions of the Cervix in Clinical Practice: A Cytology, Histology, and Human Papillomavirus Correlation Study From 2 Institutions. Arch Pathol Lab Med. 2015;139(11):1431-6.
  • Lashmanova N, Braun A, Cheng L, Gattuso P, and Yan L. Endocervical adenocarcinoma in situ-from Papanicolaou test to hysterectomy: a series of 74 cases. J Am Soc Cytopathol. 2022;11(1):13-20.
  • Bruno MT, Valenti G, Cassaro N, et al. The Coexistence of Cervical Intraepithelial Neoplasia (CIN3) and Adenocarcinoma In Situ (AIS) in LEEP Excisions Performed for CIN3. Cancers (Basel). 2024;16(5)
  • Schwock J, Ko HM, Dube V, et al. Stratified Mucin-Producing Intraepithelial Lesion of the Cervix: Subtle Features Not to Be Missed. Acta Cytol. 2016;60(3):225-31.
  • Yang EJ, Kim NR, Choi JY, Kim WY, and Lee SJ. Loop electrosurgical excision procedure combined with cold coagulation for cervical intraepithelial neoplasia and adenocarcinoma in-situ: a feasible treatment with a low risk of residual/recurrent disease. Infect Agent Cancer. 2020;15:58.
  • Bruno MT, Cavallaro AG, Fiore M, et al. Endocervical Curettage and Extended HPV Genotyping as Predictors of Residual Disease After Hysterectomy in Postmenopausal Women Previously Treated with LEEP for CIN3: A Multivariate Analysis. Cancers (Basel). 2025;17(13)
  • Akgor U, Ozgul N, Gunes AC, Turkyilmaz M, and Gultekin M. Evaluation of Endocervical Curettage in Colposcopy in the Turkish Cervical Cancer Screening Program. J Clin Med. 2024;13(15)
  • Inal HA, Han O, Ozturk Inal Z, Eren Karanis MI, and Kucukosmanoglu I. Evaluation of concordance between loop electrosurgical excisional procedure and cervical colposcopic biopsy results. J Turk Ger Gynecol Assoc. 2024;25(1):13-17.
There are 29 citations in total.

Details

Primary Language English
Subjects Gynecologic Oncology Surgery
Journal Section Research Article
Authors

Işık Sözen 0000-0002-7733-9171

Hilal Serap Arslan 0000-0002-4958-2393

Gözde Şahin 0000-0003-3067-9125

Yasemin Aboalhasan 0000-0002-6231-9223

Elif Dila Tasti 0009-0004-9034-1454

İlkbal Temel 0000-0002-7337-9977

Publication Date September 30, 2025
Submission Date September 21, 2025
Acceptance Date September 30, 2025
Published in Issue Year 2025 Volume: 16 Issue: 3

Cite

APA Sözen, I., Arslan, H. S., Şahin, G., … Aboalhasan, Y. (2025). Clinicopathological Evaluation of Patients with SMILE, Cervical Intraepithelial Neoplasia 3, and Adenocarcinoma in Situ. Turkish Journal of Clinics and Laboratory, 16(3), 625-633. https://doi.org/10.18663/tjcl.1788113
AMA Sözen I, Arslan HS, Şahin G, Aboalhasan Y, Tasti ED, Temel İ. Clinicopathological Evaluation of Patients with SMILE, Cervical Intraepithelial Neoplasia 3, and Adenocarcinoma in Situ. TJCL. September 2025;16(3):625-633. doi:10.18663/tjcl.1788113
Chicago Sözen, Işık, Hilal Serap Arslan, Gözde Şahin, Yasemin Aboalhasan, Elif Dila Tasti, and İlkbal Temel. “Clinicopathological Evaluation of Patients With SMILE, Cervical Intraepithelial Neoplasia 3, and Adenocarcinoma in Situ”. Turkish Journal of Clinics and Laboratory 16, no. 3 (September 2025): 625-33. https://doi.org/10.18663/tjcl.1788113.
EndNote Sözen I, Arslan HS, Şahin G, Aboalhasan Y, Tasti ED, Temel İ (September 1, 2025) Clinicopathological Evaluation of Patients with SMILE, Cervical Intraepithelial Neoplasia 3, and Adenocarcinoma in Situ. Turkish Journal of Clinics and Laboratory 16 3 625–633.
IEEE I. Sözen, H. S. Arslan, G. Şahin, Y. Aboalhasan, E. D. Tasti, and İ. Temel, “Clinicopathological Evaluation of Patients with SMILE, Cervical Intraepithelial Neoplasia 3, and Adenocarcinoma in Situ”, TJCL, vol. 16, no. 3, pp. 625–633, 2025, doi: 10.18663/tjcl.1788113.
ISNAD Sözen, Işık et al. “Clinicopathological Evaluation of Patients With SMILE, Cervical Intraepithelial Neoplasia 3, and Adenocarcinoma in Situ”. Turkish Journal of Clinics and Laboratory 16/3 (September2025), 625-633. https://doi.org/10.18663/tjcl.1788113.
JAMA Sözen I, Arslan HS, Şahin G, Aboalhasan Y, Tasti ED, Temel İ. Clinicopathological Evaluation of Patients with SMILE, Cervical Intraepithelial Neoplasia 3, and Adenocarcinoma in Situ. TJCL. 2025;16:625–633.
MLA Sözen, Işık et al. “Clinicopathological Evaluation of Patients With SMILE, Cervical Intraepithelial Neoplasia 3, and Adenocarcinoma in Situ”. Turkish Journal of Clinics and Laboratory, vol. 16, no. 3, 2025, pp. 625-33, doi:10.18663/tjcl.1788113.
Vancouver Sözen I, Arslan HS, Şahin G, Aboalhasan Y, Tasti ED, Temel İ. Clinicopathological Evaluation of Patients with SMILE, Cervical Intraepithelial Neoplasia 3, and Adenocarcinoma in Situ. TJCL. 2025;16(3):625-33.