The Silva Pattern-based Classification for HPV-associated Invasive Endocervical Adenocarcinoma and the Distinction Between In Situ and Invasive Adenocarcinoma: Relevant Issues and Recommendations From the International Society of Gynecological Pathologists

Abstract

The Silva pattern-based classification for human papilloma virus–associated invasive adenocarcinoma has emerged as a reliable system to predict risk of lymph node metastasis and recurrences. Although not a part of any staging system yet, it has been incorporated in synoptic reports as established by the College of American Pathologists (CAP) and the International Collaboration on Cancer Reporting (ICCR). Moreover, the current National Comprehensive Cancer Network (NCCN) guidelines include this classification as an “emergent concept.” In order to facilitate the understating and application of this new classification by all pathologists, the ISGyP Endocervical Adenocarcinoma Project Working Group presents herein all the current evidence on the Silva classification and aims to provide recommendations for its implementation in practice, including interpretation, reporting, and application to biopsy and resection specimens. In addition, this article addresses the distinction of human papilloma virus–associated adenocarcinoma in situ and gastric type adenocarcinoma in situ from their invasive counterparts.

Clear Cell Carcinoma (CCC) of the Cervix Is a Human Papillomavirus (HPV)-independent Tumor Associated With Poor Outcome

“…This has important implications regarding the differential diagnosis and management of CCC since the application of the Silva pattern classification system to HPVI ECA is currently not recommended by the International Society of Gynecologic Pathologists (ISGyP). 15 The prognosis of cervical CCC is stage-dependent, yet the inherent risk associated with this histology is not well established. While recent work has demonstrated that HPVI ECA have a worse prognosis than HPVA ECA, no study has looked specifically at a large cohort of CCC as compared with GTA.…”

“…In addition, we have observed Silva patterns A and B in cervical CCCs, particularly in small, early-stage tumors, as well as exophytic lesions. This has important implications regarding the differential diagnosis and management of CCC since the application of the Silva pattern classification system to HPVI ECA is currently not recommended by the International Society of Gynecologic Pathologists (ISGyP) 15…”

Molecular Detection Methods in HPV-Related Cancers

“…Non-HPV-related cervical cancer is rare, representing <1% of newly diagnosed cases, with histologies including cervical neuroendocrine, small cell, and large cell carcinomas ( 30 ). In comparison of the two major histologies, SCCdevelops from the ectocervix's squamous epithelia and AC develops from the endocervix'sglandular epithelia ( 29 ) Studies suggest that the incidence of AC appears to be increasing in some countries while SCC incidence is decreasing ( 29 , 47 ). The rise is seen among young women, partly due to cohort effect and partly due to cytology screening, which is less effective for detection of AC compared to SCC ( 29 ).…”

“…The rise is seen among young women, partly due to cohort effect and partly due to cytology screening, which is less effective for detection of AC compared to SCC ( 29 ). Although there is growing evidence that ACs have different epidemiology, prognostic variables, patterns of dissemination, and treatment failure following therapy compared to SCCs, both are staged and treated similarly ( 47 ). Silvaclassification, which stratifies invasion in three patterns, is used to determine HPV-related CAC ( 47 , 48 ).…”

“…Although there is growing evidence that ACs have different epidemiology, prognostic variables, patterns of dissemination, and treatment failure following therapy compared to SCCs, both are staged and treated similarly ( 47 ). Silvaclassification, which stratifies invasion in three patterns, is used to determine HPV-related CAC ( 47 , 48 ). Even though p16 expression is considered to be a surrogate marker for HPVassociation, p16 IHC testing is not absolutely necessary for the classification, and HPV analysisis not necessary for the diagnosis ( 48 ).…”