HPV 16/18 Pozitif Kadınlarda CIN3 Tanısında Sistemik Enflamatuvar Belirteçlerin Yeri: Retrospektif Bir Çalışma

Öz

ÖZET Amaç: Bu çalışmada, HPV 16 ve/veya 18 pozitif kadınlarda sistemik immün-inflamasyon indeksinin (SII) CIN3+ lezyonları bağımsız olarak öngörüp öngöremeyeceğinin değerlendirilmesi amaçlandı. Gereç ve Yöntem: Retrospektif olarak tasarlanan bu çalışmaya, kolposkopik biyopsi yapılan ve HPV 16 ve/veya 18 pozitifliği saptanan 203 kadın dahil edildi. Biyopsi öncesi tam kan sayımı parametrelerinden nötrofil-lenfosit oranı, trombosit-lenfosit oranı ve sistemik immün-inflamasyon indeksi hesaplandı. CIN3+ öngörüsünde SII’nin performansı için ROC eğrisi analizi yapıldı ve optimal eşik değer Youden indeksi ile belirlendi. Bağımsız ilişkiyi değerlendirmek amacıyla çok değişkenli lojistik regresyon analizi uygulandı. Sonuçlar: Hastaların %19,7’sinde CIN3+ saptandı. Değerlendirilen inflamatuvar belirteçler arasında yalnızca SII ile CIN3+ arasında anlamlı ilişki bulundu (p=0,004). Eğri altında kalan alan 0,647 olarak hesaplandı. 809,450 eşik değeri için duyarlılık %77,5 ve özgüllük %48,4 idi. Çok değişkenli analizde SII ≥809,450 değeri CIN3+ ile bağımsız olarak ilişkili bulundu (OR: 3,24; %95 GA: 1,45–7,23; p=0,004). Modelin açıklayıcılığı sınırlıydı (Nagelkerke R²=0,072). Tartışma: Sistemik immün-inflamasyon indeksi HPV 16 ve/veya 18 pozitif kadınlarda CIN3+ ile bağımsız olarak ilişkili bulunmuştur; ancak öngörü gücü sınırlıdır. SII, risk temelli değerlendirme modellerinde tamamlayıcı bir parametre olarak değerlendirilebilir. Anahtar Sözcükler: Servikal intraepitelyal neoplazi, insan papilloma virüsü, sistemik immün-inflamasyon indeksi, inflamasyon belirteçleri

Anahtar Kelimeler

• Servikal intraepitelyal neoplazi
• insan papilloma virüsü
• sistemik immün-inflamasyon indeksi

Destekleyen Kurum

Bu araştırma herhangi bir dış finansman almamıştır.

Etik Beyan

Bu çalışma, Afyonkarahisar Sağlık Bilimleri Üniversitesi Hastanesi Etik Kurulu tarafından onaylanmıştır (onay no: 2025/8 – tarih: 13.06.2025). Çalışma, Helsinki Bildirgesi'ne uygun olarak yürütülmüştür. Bu çalışma için gerekli kurumsal izinler, Afyonkarahisar İl Sağlık Müdürlüğü ve Afyonkarahisar Devlet Hastanesi'nden alınmıştır.

Teşekkür

Bu çalışmayı, Türkiye'de jinekolojik onkolojinin öncülerinden, bilimsel titizliği ve kadın kanseri tedavisini geliştirme konusundaki kararlılığıyla nesiller boyu klinisyen ve araştırmacıya yol gösteren Prof. Dr. Ali Ayhan'ın anısına ithaf ediyoruz.

The Association Between Systemic Inflammatory Markers and CIN3+ in Women Positive for HPV 16/18: A Retrospective Study

Öz

ABSTRACT Objective: To evaluate whether the systemic immune-inflammation index (SII) independently predicts CIN3+ lesions in women positive for HPV 16 and/or 18. Methods: This retrospective study included 203 women aged 25 to 65 years with confirmed HPV 16 and/or 18 positivity who underwent colposcopic biopsy. Pre-biopsy complete blood count parameters were used to calculate neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and SII. Receiver operating characteristic curve analysis was performed to determine the optimal SII cut-off for predicting CIN3+. Multivariate logistic regression analysis was used to assess whether SII independently predicted CIN3+ after adjustment for age, HPV genotype, and hemoglobin level. Results: Among the evaluated markers, only SII demonstrated a statistically significant association with CIN3+ (p = 0.004). The area under the curve was 0.647. An optimal cut-off value of 809.450 yielded 77.5% sensitivity and 48.4% specificity. In multivariate analysis, SII values at or above this threshold were independently associated with CIN3+ (odds ratio 3.24, 95% confidence interval 1.45 to 7.23; p = 0.004). However, the overall explanatory power of the model was limited (Nagelkerke R² = 0.072). Conclusion: SII was independently associated with CIN3+ in women positive for HPV 16 and/or 18, although its discriminatory capacity was modest. While insufficient as a standalone triage tool, SII may provide incremental value within multifactorial risk stratification models. Prospective validation studies are warranted. Keywords: Cervical intraepithelial neoplasia, human papillomavirus, systemic inflammation markers

Anahtar Kelimeler

• Cervical intraepithelial neoplasia
• human papillomavirus
• systemic inflammation markers

Destekleyen Kurum

This research received no external funding.

Etik Beyan

The present study was approved by the Ethical Committee of Afyonkarahisar Health Sciences University Hospital (grant no: 2025/8 – date: 13.06.2025). The study was conducted in accordance with the Declaration of Helsinki. The necessary institutional permissions for this study were obtained from Afyonkarahisar Provincial Health Directorate and Afyonkarahisar State Hospital.

Teşekkür

We dedicate this study to the memory of Prof. Dr. Ali Ayhan, a pioneer of gynecologic oncology in Türkiye, whose scientific rigor and commitment to advancing women’s cancer care shaped generations of clinicians and researchers.

Kaynakça

1. Sammarco ML, Tamburro M, Pulliero A, Izzotti A, Ripabelli G. Human papillomavirus infections, cervical cancer and MicroRNAs: an overview and implications for public health. MicroRNA. 2020;9(3):174-86.
2. Malagón T, Franco EL, Tejada R, Vaccarella S. Epidemiology of HPV-associated cancers past, present and future: towards prevention and elimination. Nat Rev Clin Oncol. 2024;21(7):522-38.
3. Arbyn M, Simon M, Peeters E, et al. 2020 list of human papillomavirus assays suitable for primary cervical cancer screening. Clin Microbiol Infect. 2021;27(8):1083-1095.
4. Munshi VN, Perkins RB, Sy MS, Kim JJ. Cost-effectiveness analysis of the 2019 ASCCP risk-based management consensus guidelines for the management of abnormal cervical cancer screening tests and cancer precursors. Am J Obstet Gynecol. 2022;226(2):228.e1.
5. Nayar R. Precision Prevention: The 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors. J Mol Pathol. 2021;2(3):274-80.
6. Dai W, Guo C, Yang Q, et al. Validation of the 2019 American Society of Colposcopy and Cervical Pathology Online Cervical Cancer Screening Program via 9 Large-Cohort Data of Chinese Women. J Low Genit Tract Dis. 2024;28(2):e34-e39.
7. Karaçor T, Sak S, Barut MU, Peker N, Sak ME. Yüksek Riskli HPV Pozitif Sitolojik Sonuçların, Kolposkopik Biyopsi Sonuçları İle Karşılaştırılması. Harran Univ Med J. 2019;16(3):540-4.
8. Julián RC, MRZ J. Rudolf Virchow: requiem for a visionary. Curr Inv Cln Med Res. 2021;1(1):1-5. Chao B, Ju X, Zhang L, Xu X, Zhao Y. A novel prognostic marker systemic inflammation response index (SIRI) for operable cervical cancer patients. Front Oncol. 2020;10:766.

9. Zhu M, Feng M, He F, Han B, Ma K, Zeng X, et al. Pretreatment neutrophil-lymphocyte and platelet-lymphocyte ratio predict clinical outcome and prognosis for cervical cancer. Clin Chim Acta. 2018;483:296-302.
10. Inturrisi F, Bogaards JA, Heideman DA, Meijer CJ, Berkhof J. Risk of cervical intraepithelial neoplasia grade 3 or worse in HPV-positive women with normal cytology and five-year type concordance: a randomized comparison. Cancer Epidemiol Biomarkers Prev. 2021;30(3):485-91.
11. Cim N, Ayguler E, Gunal N, Cim B, Atalmis HA, Cetin A. Systemic Inflammatory Response Index in Cervical Pathologies (Human Papillomavirus and Cervical Neoplasia) and its Prognostic Value in Disease Prediction. Niger J Clin Pract. 2025;28(5):615-23.
12. Qin L, Zhang L. The predictive value of serum inflammatory markers for the severity of cervical lesions. BMC Cancer. 2024;24(1):780.
13. Sadri NJ, Moghoofei M, Salmaninejad A, et al. Pathogenic role of exosomes and microRNAs in HPV-mediated inflammation and cervical cancer: a review. Int J Cancer. 2020;146(2):305-20.
14. Ilhan ZE, Łaniewski P, Thomas N, et al. Deciphering the complex interplay between microbiota, HPV, inflammation and cancer through cervicovaginal metabolic profiling. EBioMedicine. 2019;44:675-90. Tas M, Yavuz A, Ak M, Ozcelik B. Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Discriminating Precancerous Pathologies from Cervical Cancer. J Oncol. 2019;2019:2476082.
15. Wang B, Huang Y, Lin T. Prognostic impact of elevated pre-treatment systemic immune-inflammation index (SII) in hepatocellular carcinoma: a meta-analysis. Medicine (Baltimore). 2020;99(1):e18571. Holub K, Biete A. Impact of systemic inflammation biomarkers on the survival outcomes of cervical cancer patients. Clin Transl Oncol. 2019;21(7):836-44.
16. Ozdemir CY, Cicekli N, Ahat B, et al. Effect of hemoglobin, albumin, lymphocyte, and platelet score on prognosis in intermediate-risk endometrial cancer according to molecular-based classification. J Obstet Gynaecol Res. 2024;50(11):2107-2112.
17. Staniewska E, Grudzien K, Stankiewicz M, et al. The prognostic value of the systemic immune-inflammation index (SII) and red cell distribution width (RDW) in patients with cervical cancer treated using radiotherapy. Cancers (Basel). 2024;16(8):1542.