Cervical adenocarcinoma risk stratification using histotype and invasion pattern: a multicenter retrospective study...

To validate the clinical utility of the Silva classification (a risk-stratification system based on invasion pattern for HPV-associated cervical adenocarcinoma; HPVA) using Japanese cohort data; and to determine how HPV-independent adenocarcinoma (HPVI) should be positioned relative to Silva-classified HPVA.

We retrospectively analyzed 264 cases of surgically treated FIGO 2008 stage I-II cervical adenocarcinoma from eight institutions participating in the KAMOGAWA Study. Tumors were classified as HPVA or HPVI. HPVA cases were further categorized as low-risk or high-risk using the binary Silva classification, which incorporates invasion pattern and lymphovascular space invasion. Outcome measures included lymph node metastasis, disease-free survival (DFS), and overall survival (OS).

Of the 264 cases, 27 % were classified as low-risk HPVA, 49 % as high-risk HPVA, and 23 % as HPVI. Lymph node metastasis was observed in 0 %, 12 %, and 38 % of cases, respectively (p < 0.001). The 5-year DFS was 98 %, 83 %, and 53 %, and the 5-year OS was 100 %, 97 %, and 63 % (both p < 0.001). Multivariable analysis showed that low-risk HPVA was associated with longer DFS (HR 0.12, 95 % CI 0.015-0.87) and HPVI was associated with shorter DFS (HR 2.76, 95 % CI 1.44-5.30), after adjusting for tumor size (≤2 cm, 2-4 cm, >4 cm) and age. Tumor size >4 cm, but not ≤2 cm was an independent prognostic factor.

The three-tier system combining the histotype and binary Silva classification outperformed tumor size in prognostic stratification. The low-risk group showed excellent outcomes, supporting the potential for conservative management such as uterine preservation after conization.