Stromal invasion pattern identifies patients at lowest risk of lymph node metastasis in HPV-associated endocervical adenocarcinomas, but is irrelevant in adenocarcinomas unassociated with HPV

• Published in: Gynecologic oncology Vol. 150; no. 1; pp. 56 - 60
• Main Authors: Stolnicu, S., Barsan, I., Hoang, L., Patel, P., Terinte, C., Pesci, A., Aviel-Ronen, S., Kiyokawa, T., Alvarado-Cabrero, I., Oliva, E., Park, K.J., Abu-Rustum, N.R., Pike, M.C., Soslow, R.A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2018
• Subjects: Adenocarcinoma - mortality; Adenocarcinoma - pathology; Cervical cancer; Female; Human papillomavirus; Humans; Lymphatic Metastasis - immunology; Lymphovascular invasion; Metastasis; Neoplasm Recurrence, Local; Papillomaviridae - pathogenicity; Papillomavirus Infections - pathology; Pathology; Recurrence; Risk Factors; Survival Rate; Uterine Cervical Neoplasms - mortality; Uterine Cervical Neoplasms - pathology; Pathology; Recurrence; Human papillomavirus; Metastasis; Cervical cancer; Lymphovascular invasion
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2018.04.570

The Silva invasion pattern-based classification system stratifies endocervical adenocarcinomas (ECAs) into 3 categories corresponding to risk of metastasis and recurrence, but has only been evaluated for HPV-associated ECAs of usual type. We examined whether the Silva system is applicable to all endocervical adenocarcinomas, especially those not associated with HPV. Complete slide sets from 341 surgical specimens of ECA were collected from 7 institutions worldwide. All specimens were associated with clinical records covering at least 5 years of follow-up. Tumors were classified as HPV-associated (HPVA) or not (NHPVA) by both morphology and detection of HPV using in situ hybridization. Recurrence and survival were analyzed by multivariate Mantel-Haenszel methods. Most specimens (292; 85.6%) were HPVA, while 49 (14.3%) were NHPVA. All NHPVAs were Silva pattern C, while 76.0% of HPVAs were pattern C, 14.7% pattern A, and 9.3% pattern B. Including both HPVAs and NHPVAs, lymphovascular invasion (LVI) was detected in 0% of pattern A, 18.5% of pattern B and 62.6% of pattern C cases (p < 0.001). None of the pattern A or B cases were associated with lymph node metastases (LNM), in contrast to pattern C cases (21.8%). Among patients with Silva pattern C ECA, those with HPVA tumors had a lower recurrence rate and better survival than those with NHPVA; however, when adjusted for stage at diagnosis, the difference in recurrence and mortality was small and not statistically significant. Application of the Silva system is only relevant in HPVA cervical adenocarcinoma. •We confirm that pattern A and B HPV-associated endocervical adenocarcinomas (HPVA) lacking LVI are not associated with LNM.•Compared to HPVA, non-HPV-associated (NHPVA) endocervical adenocarcinomas (ECAs) are larger and more invasive.•For NHPVA ECAs, risk of lymph node metastasis is determined by clinical stage, not by age or tumor size or morphology.•All NHPVA ECAs belong to the most invasive Silva pattern, so that classification system is irrelevant to these tumors.