Detection of human papillomavirus deoxyribonucleic acid from vulvar dystrophies and vulvar intraepithelial neoplastic lesions

Mickey Karram, MD, Bannie Tabor, MD, David Smotkin, MD, PhD, Felix Wettstein, PhD, Narender Bhatia, MD, and John Micha, MD

Los Angeles, California

Vulvar biopsy specimens from 16 patients with gross lesions of the vulva consistent with vulvar dystrophy were examined histologically and for the presence of human papillomavirus deoxyribonucleic acid by southern blot hybridization. None of the nonatypical dystrophies probed positive for human papillomavirus; however, three of five atypical hyperplastic dystrophies (vulvar intraepithelial neoplasia) contained human papillomavirus deoxyribonucleic acid type 16. We conclude that human papillomavirus does not seem to be a causal factor in nonatypical chronic epithelial changes of the vulva. (AM J OssTET GvNECOL 1988;159:22-3.)

Key words: Dystrophy, vulvar intraepithelial neoplasia, human papillomavirus

The term dystrophy describes a disorder of epithelial growth and nutrition. Why chronic epithelial changes of vulvar skin occur in certain patients is not known, nor is why a small percentage of these lesions will have or develop varied amounts of atypia. Human papillo­mavirus is being isolated with increasing frequency throughout the female genital tract. Certain subtypes of this virus have been isolated in high percentages in premalignant and malignant conditions of the cervix and vulva.

The following study was undertaken to assess the presence of human papillomavirus deoxyribonucleic acid (DNA) in chronic epithelial changes of the vulva without atypia (dystrophy) and with atypia (vulvar in­traepithelial neoplasia).

Material and methods

Eighteen patients consecutively seen at the vulva clinic at Harbor University of California Los Angeles Medical Center with symptomatic lesions of the vulva grossly consistent with vulvar dystrophy were entered into the study.

Adjacent biopsy specimens were obtained from the most severe-appearing areas of the vulva and sent for histologic examination for the presence of human pap­illomavirus DNA (types 6, 11, 16, and 18) by Southern blot hybridization.'

From the Department of Obstetrics and Gynecolog)', Harbor/ Univer­sity of California, Los Angeles Medical Center and Cedars-Sinai Medical Center, University of California, Los Angeles School of Medicine.

Received for publication September 24, 1987; revi1ed November 13, 1987; accepted December 15, 1987.

Reprint requests: Mickey M. Karram, MD, Department of Obstetrics and Gynerology, Harbor/ UCLA Medical Center, Torrance, CA 90509.

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Diagnosis of dystrophy was based on histologic cri­teria established by the International Society for the Study of Vulvar Disease.2

Results

Histologic findings. Sixteen of the 18 patients had biopsy specimens on histologic examination consistent with a vulvar dystrophy; 5 had lichen sclerosis, IO had hyperplastic dystrophy, and l had mixed findings. Five of the hyperplastic dystrophies were atypical; three were classified as vulvar intraepithelial neoplasia stage III, one as stage II, and one as stage I. None of the nonatypical dystrophies showed evidence of koilocy­tosis, whereas four of the five atypical lesions contained koilocytic cells.

Detection of human papillomavirus DNA by South· em blotting. None of the atrophic, nonatypical hyper­plastic or mixed dystrophies probed positive for any of the types of human papillomavirus being tested. How­ever, all three vulvar intraepithelial neoplasia stage III lesions probed positive for human papillomavirus type 16.

Comment

This study found no correlation between chronic epithelial changes of the vulva-whether they be lichen sclerosis or nonatypical, hyperplastic, or mixed dystrophies-and human papillomavirus infection. However, evidence continues to accumulate showing a frequent association of premalignant forms of human papillomavirus with vulvar intraepithelial neoplasia. Pilotti et al.' reported a series of l 0 cases of vulvar carcinoma in situ and noted a 70. 7% association with human papillomavirus infection. Crum et al:' reported 41 cases of vulvar intraepithelial neoplasia and found associated human papillomavirus in 55.5% of their

Volume 159 Number I

cases. Although in our study there were only five pa­tients with vulvar intraepithelial neoplasia lesions, all three stage III lesions probed positive for human pap­illomavirus type 16.

All varieties of dystrophy share the hallmarks of chronicity, pruritis, and architectural change. Although progression rates of these conditions are generally low (<5%), the course in the individual patient is unpre­dictable. The literature quotes a 10% association of dys­plasia or atypia with hyperplastic lesions of the vulva. However, in this study it was noted that 5 of I 0 patients (50%) had vulvar lesions grossly and histologically con­sistent with hyperplastic dystrophy that were atypical or dysplastic. This increased prevalance of vulvar in­traepithelial neoplasia in our study may reflect a higher prevalance of human papillomavirus. Whether human papillomavirus induces dysplastic changes in a preex­isting hyperplastic epithelium, or viral infection of nor­mal epithelium induces an atypical hyperplastic reac­tion, remains to be demonstrated.

Vulvar dystrophy and human papillomavirus

In conclusion, our study found no relationship be­tween common subtypes of human papillomavirus and vulvar dystrophies. However, a high frequency of hu­man papillomavirus type 16 (60%) was noted in vulvar intraepithelial neoplasia.

REFERENCES

I. Smotkin D, BerekJS, Fu YS, et al. Human papillomavirus deoxyribonucleic acid in adenocarcinoma and adenosqua­mous carcinoma of the uterine cervix. Obstet Gynecol 1986;68:24 l.

2. Wilkenson E.J, Kneale B, Lynch PJ. Report of the ISSVD Terminology Committee . .J Reprod Med I 986;20:973.

3. Pilotti S, Rilke F, Shah K, et al. Immunohistochemical and ultrastructural evidence of HPV infection associated with in situ and microinvasive squamous cell carcinoma of the vulva. Am J Surg Pathol 1984;8:75 I.

4. Crum CP, Liskow A, Petras P, et al. VIN (severe atypia and carcinoma in situ). A clinicopathologic study of 41 cases. Cancer 1984;54:1429.

In utero ischemic injury: Sonographic diagnosis and medicolegal implications

Ronald A. Stoddard, MD, Steven L. Clark, MD, and Stephen D. Minton, MD

Provo, Utah

The antenatal diagnosis of fetal neurologic injury has profound medical and legal implications. We report a

case of antenatally diagnosed intracranial lesions including parenchymal hemorrhage in an otherwise physically normal infant. Computerized tomography in the newborn period demonstrated diffused ischemic

damage with secondary cystic changes in addition to intracranial hemorrhage. (AM J OssrEr GYNECOL

1988;159:23-5.)

Key words: Antenatal diagnosis, fetal intracranial hemorrhage, medicolegal considerations

Improvements in ultrasound technology combined with increasing imaging skills have allowed an increas­ingly thorough evaluation of the fetus. Recent reports have documented the diagnosis of cerebral vascular hemorrhage in utero as well as congenital hydroceph­alus secondary to unexplained fetal intraventricular hemorrhage ... 2 In addition, approximately 6% of still­born fetuses have intracranial hemorrhage diagnosed at autopsy. Medicolegal considerations make the doc­umentation of any type of prenatal neurologic injury

From the Utah Valley Regional Perinatal Center. Receivedforpublication May 18, 1987; revised November 13, 1987;

accepted January 25, 1988. Reprint requests: Ronald A. Stoddard, MD, Utah Valley Regional

Perinatal Center, 1034 N. 500 West, Provo, UT 84604.

extremely important. We report here a Ji,·e-born infant in whom intracranial hemorrhage and diffuse ischemic injury were documented before labor.

Case report The infant was the 1215 gm female product ofa 34-

week pregnancy in a 32-year-old mother (gravida 6, para 5). The pregnancy had been unremarkable, with no history of medication, significant illness, or trauma. Real-time ultrasound (5 MHz, General Electric RT-3000) performed for size I dates discrepancy showed symmetric intrauterine growth retardation with oligohydramnios. Also noted was evidence of fetal left periventricular hemorrhage and a smaller right in­tra ventricular hemorrhage (Fig. 1).

The mother underwent a nonstress test that was non-

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