HPV-independent Differentiated Vulvar Intraepithelial Neoplasia (dVIN) is Associated With an Aggressive Clinical Course.
Differentiated vulvar intrapeithelial neoplasia (dVIN) is an human papillomavirus (HPV)-independent precursor of squamous cell carcinoma (SCC), and the aim of this study was to better characterize its natural history. Cases of dVIN were identified from the pathology archives. Outcomes of patients with dVIN only, without associated invasive SCC, were compared with a cohort of patients with high-grade squamous intraepithelial lesion [HSIL(VIN3)]. Eighteen patients diagnosed with dVIN with adjacent invasive SCC (SCC/dVIN) and 7 patients with dVIN only, without invasive carcinoma, were identified. Mean age in both cohorts was 75 yr. All lesions but 1 were unifocal. In 35% of SCC/dVIN cases the surgical resection margins were positive for SCC, with 75% and 60% having margins positive for dVIN in the SCC/dVIN and dVIN-only cohorts, respectively. In total, 23/25 women with dVIN only or dVIN/SCC, for whom there was follow-up information, experienced either progression to or recurrence of invasive SCC, respectively, at a median of 1.1 yr, including all but 1 case of dVIN only, where the median time of progression to invasive SCC was 1.9 yr. A total of 22/25 women died of disease with a median overall survival of 3.4 yr. The outcome (i.e. progression to invasive carcinoma) of patients with dVIN only was significantly worse than that of a comparison group of 18 patients with HSIL(VIN3) (progression-free survival log-rank, P<0.001; disease-specific survival, P=0.04; overall survival, P=0.01). Six of 7 patients with dVIN only developed invasive carcinoma on follow-up, compared with 0 of 18 patients with HSIL(VIN3). The diagnosis of dVIN indicates the presence of a high-risk human papillomavirus-negative precursor of invasive SCC. These patients are likely to progress to invasive carcinoma over a relatively short period, at which point their prognosis is guarded.
Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia (J.N.M., S.Y.K., D.M.M.) Department of Pathology and Laboratory Medicine, University of British Columbia and BC Cancer Agency (A.A., S.E., C.B.G.) Vancouver, BC, Canada Department of Applied Tumor Biology, Institute of Pathology, University of Heidelberg, and Clinical Cooperation Unit Applied Tumor Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany (M.R., M.v.K.D., E.S.P.) Department of Cellular Pathology, Barts and the London NHS Trust, London, UK (S.J., N.S.).
Jessica N
JN
McAlpine
So Youn
SY
Kim
Ardalan
A
Akbari
Sima
S
Eshragh
Miriam
M
Reuschenbach
Magnus
M
von Knebel Doeberitz
Elena S
ES
Prigge
Suzanne
S
Jordan
Naveena
N
Singh
Dianne M
DM
Miller
C Blake
CB
Gilks
D000368:Aged; D002278:Carcinoma in Situ / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000473:pathology*; D014846:Vulvar Neoplasms / Q000473:pathology*