© 1999 ASCCP, 1089-2591/99/$14.00/0 Journal of Lower Genital Tract Disease, Volume 3, Number 2, 1999 98–103 Reproducibility of the Histopathological Classification of Vulvar Squamous Carcinoma and Intraepithelial Neoplasia C. L. Trimble, MD,* M. Diener-West, PhD, † E. J. Wilkinson, MD, ‡ R. J. Zaino, MD, § R. J. Kurman, MD,  and K. V. Shah, MD, DrPH # *Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD; † Department of Biostatistics, Johns Hopkins University School of Public Health, Baltimore, MD; ‡ Department of Medicine and Laboratory Pathology, University of Florida, College of Medicine, Gainesville, FL; § Hershey Medical Center, Pennsylvania State University, Hershey, PA;  Departments of Gynecology and Obstetrics and of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD; and # Department of Molecular Microbiology and Immunology, Johns Hopkins University School of Public Health, Baltimore, MD ries were combined. Good agreement was achieved (kappa values of 0.55–0.79) in distinguishing human papillomavirus– related lesions from those unrelated to human papillomavi- rus; all three reviewers agreed on this classification for 67% of the cases. The intrareviewer agreement was of the same order as interreviewer agreement. Difficulties in differentiating be- tween some lesions (e.g., a warty carcinoma with little atypia from a well- to moderately differentiated keratinizing squa- mous carcinoma) and concurrent occurrence of human papil- lomavirus–related lesions and those lesions unrelated to hu- man papillomavirus in a patient may account for some of the discrepancies in the histopathological diagnoses of vulvar car- cinoma.  Key Words: histopathology, human papillomavirus, reproduc- ibility, vulvar carcinoma, vulvar intraepithelial neoplasia S everal recent reports characterize squamous carci- noma of the vulva into those that are most likely re- lated to human papillomaviruses (HPVs) and those that are not [1–6]. HPV-associated vulvar carcinomas have  Abstract: Invasive vulvar carcinoma has been shown to be etiologically heterogeneous on the basis of pathological, viro- logical, and epidemiological criteria. Human papillomavirus– related invasive vulvar carcinoma has basaloid or warty mor- phology and has adjacent basaloid or warty intraepithelial neoplasia. Invasive carcinoma unrelated to human papilloma- virus is a keratinizing squamous carcinoma that may have adja- cent squamous hyperplasia. We provided to 3 pathologists for their review and pathological diagnoses stained tissue sections from 95 patients with vulvar carcinoma. The reproducibility for grading individual categories of intraepithelial lesions was only fair (kappa values of 0.31–0.43). The reproducibility was better (moderate to good; kappa values of 0.58–0.59) for grading individual categories of invasive carcinomas. The agreements improved when the basaloid and warty catego- Reprint requests to: Dr. Keerti Shah, 615 North Wolfe Street, Balti- more, MD 21205.