Our study indicated that patients with Silva A pattern tumors often have favorable outcomes, positively related with the oncology prognosis of endocervical adenocarcinoma, while those with Silva C tumors often have worse outcomes. Our study found no clear correlation between Silva C and the oncology prognosis of endocervical adenocarcinoma.

This meta-analysis suggests that Silva A classification is associated with prognosis for endocervical adenocarcinoma. Roma et al11–13 reported that 21% of patients (73/352) had pattern A tumor, all stage I, and no recurrence. These results are consistent with previous studies.5 6 12 17 32 Genomic profiling studies have found that pattern A tumors tend to lack oncogenic changes, indicating that they may represent a less aggressive sub-set of endocervical adenocarcinoma or an early stage in tumor progression.33 These studies support the view that patients with Silva A tumors have a good prognosis. However, Feinberg et al34 described eight rare cases of ovarian metastases from pattern A endocervical adenocarcinoma and found a greater proportion (80%) of KRAS mutation in pattern A endocervical adenocarcinoma, which led them to think that certain gene mutations may be associated with a risk for ovarian metastases. However, the data are limited and more research is needed to understand the role of gene mutations in pattern A endocervical adenocarcinoma with metastases.

Patients with Silva A endocervical adenocarcinoma often have favorable outcomes. If a pattern A tumor persists in the cone and the margins are negative, the patient may be managed with observation; if the tumor involves the surgical margins of the cone, a second cervical conization or wider excision could be necessary; if the margin of the second surgery shows a Silva B or C pattern, treatment should be followed based on the result of the second surgery. Moreover, according to this new system, one does not need to distinguish between adenocarcinoma in situ and pattern A endocervical adenocarcinoma as they undergo the same treatment and have an excellent prognosis,12 addressing the problem mentioned in some studies that a clear distinction between endocervical adenocarcinoma and adenocarcinoma in situ is not possible in up to 20% of cases.35 36

We also found that Silva C classification was negatively associated with the prognosis of endocervical adenocarcinoma. Roma et al12 reported that 53.7% of patients (189/352) had a pattern C tumor, with 61.9% of patients showing evidence of lymphovascular invasion, 21.5% patients had recurrence, and 9.5% (18/189) died from the disease. These results were similar to those of other studies.5 6 12 17 32 However, Alvarado-Cabrero et al24 divided 189 patients with pattern C endocervical adenocarcinoma into six groups and found that not all pattern C endocervical adenocarcinoma had an aggressive behavior. Xu et al23 stratified pattern C tumors into four sub-groups and found that different growth patterns showed variations in the risk of lymphovascular invasion. A study based on genomic profiles reported that pattern B and pattern C tumors have multiple oncogenic mutations such as PIK3CA, KRAS, and ERBB2.33 Given these findings, it is recommended that patients with Silva C tumors, characterized by diffuse destructive stromal invasion, should undergo adjuvant treatment.12

Our review of available studies suggests that there is no clear link to prognosis in patients with Silva B tumors, leading to more uncertainty in their treatment. Roma et al11–13 reported that only four of 90 patients with pattern B tumors had lymphovascular invasion. All patients had clinical stage I tumor and only one patient experienced a vaginal recurrence. Similar findings were reported in other studies,5 6 12 17 32 supporting the view that the Silva B classification is relatively uncertain. In addition, Sharma et al26 found that pattern B tumors with lymphovascular invasion clustered with pattern C, whereas pattern B tumors without lymphovascular invasion approached pattern A genotypically. They consolidate the Silva classification into low-risk (pattern A and pattern B without lymphovascular invasion) and high-risk (pattern B with lymphovascular invasion and pattern C) and found that high-risk tumors were enriched in mutations in PIK3CA, ATRX, and ERBB2.

Thus, the characteristic of Silva B tumors is focal destructive stromal invasion, mainly from tumor glands of Silva A structure, with or without lymphovascular invasion. Therefore, on the basis of cold knife conization, loop electrosurgical excision, or cervical resection, lymph node sampling should be performed simultaneously. As suggested by Roma et al, if sentinel lymph nodes are positive or reassessed as Silva C, radical hysterectomy should be chosen and lymph node dissection and post-operative radiotherapy and chemotherapy should be performed as appropriate.12 Patients with reassessed pattern A only need follow-up.12

The prognostic value of the Silva classification for HPV-related endocervical adenocarcinoma is controversial, with some studies showing a correlation with overall survival and disease-free survival while others report no correlation. Thus, further studies are warranted for investigating the correlation between the Silva pattern-based classification and HPV-related endocervical adenocarcinoma. According to Zeng et al,37 multivariate analysis showed that the Silva pattern system provided independent risk factors for prognosis. However, Li et al30 found that the Silva classification showed no correlation with overall survival and disease-free survival and concluded that it is helpful for selecting the appropriate operation before surgery but that its prognostic value requires further evaluation.

In a prior study, Li et al29 concluded that the Silva classification system could predict the lymph node status and prognosis of HPV-related endocervical adenocarcinoma, but that it cannot be used alone as a guideline for treatment and prognosis and should be combined with the patient’s clinical stage and other high-risk factors. Therefore, based on Silva pattern-based classification, some researchers tried to establish new models to guide the treatment of HPV-related endocervical adenocarcinoma. Li et al32 presented a second-generation system called the Silva cumulative score, and provided evidence for its potential value to predict overall survival and disease-free survival in HPV-related endocervical adenocarcinoma. They suggested that the Silva cumulative score system could be useful for more precise therapeutic trials in HPV-related endocervical adenocarcinoma. Guo et al17 reported a Silva-based 4-factor model (Silva C, ≥3 cm, depth of stromal invasion >2/3, and >mild lymphovascular invasion) specifically for patients with intermediate-risk endocervical adenocarcinoma which has a superior recurrence prediction performance to the Sedlis criteria, so it may better guide post-operative adjuvant therapy.

To the best of our knowledge, this is the first meta-analysis to focus on the relationship between the Silva pattern-based classification and oncology prognosis, and pathological features of HPV-related endocervical adenocarcinoma. However, this study has several limitations. One potential weakness is that all the included studies were retrospective, which inherently comes with some limitations. Additionally, the included studies had varying follow-up periods, making it difficult to accurately analyze 5-year overall survival or disease-free survival. Furthermore, we only included studies conducted in English, which potentially introduces language bias into our findings.