Low-Grade Vulvar and Vaginal Intraepithelial Neoplasia: Correlation of Histologic Features with Human Papillomavirus DNA Detection and MIB-1 Immunostaining

Abstract

Histologic criteria of low-grade vulvar/vaginal intraepithelial neoplasia (VIN1/VAIN1) are well established; however, a significant interobserver variability in diagnosing VIN1/VAIN1 has been reported. The goal of this study was to evaluate the utility of MIB-1 immunostaining as an adjunct test to increase the diagnostic accuracy in equivocal cases of VIN1/VAIN1. The second goal was to examine the distribution of low-and high-oncogenic risk human papillomaviruses (HPVs) in VIN1/VAIN1 lesions. Consecutive vulvar/vaginal biopsies originally diagnosed as VIN1/VAIN1 (n ‫؍‬ 43) or benign (n ‫؍‬ 20) were reviewed by two pathologists to obtain a consensus diagnosis. The diagnosis was further confirmed with HPV testing using Short PCR Fragment 10 and Line Probe Assay. MIB-1 immunostaining was performed, and positive staining was defined as a cluster of two or more stained nuclei in the upper two thirds of the epithelial thickness. After verification of the diagnosis using the consensus histologic review and HPV detection as an objective confirmatory test, 31% of cases originally diagnosed as VIN1/VAIN1 were identified as being overdiagnosed. The sensitivity and the specificity of MIB-1 staining for identifying VIN1/VAIN1 were 0.96 and 0.90, respectively. Seventy percent of VIN1 cases were associated with low-risk viral types. In contrast, the majority (84%) of VAIN1 cases were associated with high-risk HPVs. In conclusion, MIB-1 staining is sensitive and specific for identifying VIN1/VAIN1, helpful in verifying the diagnosis in equivocal cases.

The utility of the human papillomavirus DNA load for the diagnosis and prediction of persistent vaginal intraepithelial neoplasia

“…A previous study reported that 84% of VAIN 1 lesions were associated with HR HPV DNA. 14 In this study, we found that 74.3% of VAIN 1, 85.7% of VAIN 2 and 100% of VAIN 3 lesions were associated with HR HPV DNA.…”

Human papillomavirus in vaginal intraepithelial neoplasia

“…8,16 Therefore, we used Ki-67 for supporting diagnosis of VAIN, where Ki-67 staining was positive in 98.8% of the VAIN samples. Logani et al 12 included only HPV-positive cases as confirmed cases of VAIN (n ¼ 18), which resulted in 100% HPV positivity. Two other series (n ¼ 74, 111) reported similar lower HPV positivities, 82.4% and 83%, respectively.…”

“…Ki-67 immunohistochemical staining was performed to support the histological diagnosis especially for VAIN1. 12 The tissue array for each formalin-fixed, paraffin-embedded specimen was subjected to autoclave antigen retrieval at 121 C for 10 min in Trilogy TM (Cell Marque, Rocklin, CA) and incubated in an automated stainer (Ventana Medical Systems, Tucson, AZ). A Ki-67 mouse monoclonal antibody (Dako, Carpinteria, CA) was used at a dilution of 1:100, and the samples were stained with diaminobenzidine chromogen and counterstained with hematoxylin.…”

“…A Ki-67 mouse monoclonal antibody (Dako, Carpinteria, CA) was used at a dilution of 1:100, and the samples were stained with diaminobenzidine chromogen and counterstained with hematoxylin. The presence of nuclear staining in the upper two-thirds of the epithelium was interpreted as a positive result 12 (Fig. 1).…”

“…1,[4][5][6][7] Previous studies regarding HPV types in VAIN and vaginal cancer or comparisons of HPV types between incident vaginal and previous cervical lesions were limited by small sample sizes and inconsistent conclusions. 3,4,[8][9][10][11][12][13][14][15] Smith et al 8 published a systemic review of 725 abstracts, in which the HPV detection rates among 166 cases of VAIN2/3 and 66 cases of VAIN1 were 92.6% and 98.5%, respectively. Another systemic review of 22 U.S. studies found HPV16/18 to be the predominant type in VAIN3 (n ¼ 97, 65.1%).…”