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Intraepithelial squamous lesions of the vulva: biologic and histologic criteria for the distinction of condylomas from vulvar intraepithelial neoplasia.

We reviewed 65 intraepithelial lesions of the vulva and distal vagina and compared the presence of koilocytosis, abnormal mitoses, and parabasal or basal nuclear enlargement with DNA microspectrophotometric distribution patterns and the presence of human papillomavirus antigen as determined by immunoperoxidase. Abnormal mitoses and cytologically atypical nuclear enlargement were specific predictors of aneuploidy and were reliable for distinguishing vulvar intraepithelial neoplasia (VIN) from condylomas. Koilocytosis was present in 100% of condylomas and 71% of aneuploid (VIN) lesions, but there were qualitative and quantitative differences in the distribution of koilocytic cells in the two classes of lesions. On the basis of these findings, criteria for distinguishing between VIN and condyloma are proposed.

Antigens, Viral↗

Superficial laser vulvectomy. I. The efficacy of extended superficial ablation for refractory and very extensive condylomas.

Sixteen refractory (present for more than 1 year) and 16 very extensive (affecting greater than 60% of the vulva or multiple lesions greater than 1 cm) condylomas were treated by superficial carbon dioxide laser ablation of all papillomavirus-infected epithelium within the lower genital tract. Accurate depth control was maintained by using a special surgical technique to create a plane that limited penetration to the basement membrane. All patients were healed within 3 to 5 weeks, without scarring or significant complications. Of 16 patients with extensive condylomas, 15 were cured by the first laser therapy and the other patient by a second treatment. In contrast, only five of 16 refractory condylomas responded to the first operation, seven to a second procedure and another three to a third treatment. Thirty-one of these 32 patients were finally cured by superficial laser vulvectomy. The other patient required deep dermal destruction and skin grafting. This 97% eventual success rate is encouraging, particularly since there are no other satisfactory alternatives in such difficult cases.

Adolescent↗

Colposcopy in the diagnosis of penile condyloma.

To determine the incidence of penile condyloma in a group of high-risk men, we carried out colposcopy and biopsy of suspicious lesions in 51 men. All men were partners of women with condyloma. Of these men, 45 were found to have histologic evidence of condyloma, and only eight of these had grossly visible disease.

Adult↗

Cervical intraepithelial neoplasia and condyloma: an analysis of diagnostic accuracy of posttreatment follow-up methods.

The appropriate follow-up method of patients treated for cervical intraepithelial neoplasia and condyloma is controversial. One school of thought favors cytologic testing alone, whereas the other favors cytologic testing combined with colposcopy. We have analyzed the records of 750 patients treated for cervical intraepithelial neoplasia or condyloma or both in our Colposcopy Clinic. Cytologic testing, colposcopy, and histologic examination were done routinely at 3 to 4, 6 to 8, and 12 to 15 months after treatment of the above conditions in 750 patients. Totals of 95% and 5% of all 128 persistent lesions were detected by histologic examination at the first (3 to 4 months) and second (6 to 8 months) posttreatment visits, respectively. The combined false negative rates for both visits were 23% for cytologic testing, 8% for colposcopy, and 5% for histologic examination. False negative rates at first visits were 1.5% for colposcopy combined with cytologic testing. These observations suggest that colposcopy and, if appropriate, histologic examination significantly contribute to cytologic testing for diagnosing the majority of persistent disease during the first posttreatment visit. Cytologic testing alone seems to be sufficient for the subsequent follow-up of patients treated for cervical intraepithelial neoplasia and/or condyloma.

Biopsy↗

Magnified penile surface scanning in diagnosis of penile condyloma.

To determine the incidence of penile condyloma in a group of high risk males, we have performed magnified penile surface scanning and biopsy of suspicious lesions in 51 men. All men were partners of women with proven condyloma. Of these men, 45 were found to have histologic evidence of condyloma, only 8 of which were grossly visible.

Adult↗

Carbon dioxide laser therapy of subclinical condyloma found by magnified penile surface scanning.

The etiology and treatment of condyloma caused by the human papilloma virus (HPV) and the association of HPV with cervical dysplasia and/or carcinoma is a major issue in current gynecologic literature. This study examined results of carbon dioxide (CO2) laser treatment of 127 high-risk males with biopsy-proved subclinical HPV infections found by magnified penile surface scanning (MPSS). At a mean follow-up of four months a 66 per cent recurrence rate of microscopic condyloma was encountered. A discussion of the causes of such a high recurrence rate is given, with conclusions on this and prior condyloma treatment series.

Condylomata Acuminata↗

Urethroscopy and urethral cytology in men with external genital condyloma.

OBJECTIVE: To develop guidelines as to which asymptomatic male patients with genital human papillomavirus (HPV) infection need further evaluation of the urethra, we studied two screening methods: urethroscopy and voided urethral cytology. METHODS: In a four-year period, 135 asymptomatic men underwent complete screening for HPV infection. They were evaluated because of HPV-related genital disease in their female sex partners or visible genital lesions, or both. RESULTS: Of the 135 patients, 21 (16%) had no clinical, subclinical, cytologic, or urethroscopic evidence of disease, and 114 (84%) had biopsy-proven HPV infection. Of these 114 patients, only 14 (12.3%) had intraurethral condyloma. All of these 14 patients had current or historical evidence of meatal or perimeatal "sentinel" lesions. They constituted 29.8 percent of 47 such patients with sentinel lesions. In 5 patients (4%), results of voided urine cytology were positive for condyloma cells, but only 1 of these had visible intraurethral disease. Of the 14 patients with urethral disease, only 1 (7%) had positive results of urine cytology. CONCLUSIONS: These observations suggest that any asymptomatic male patient undergoing screening for condyloma acuminatum who has a history of or demonstrable subclinical or grossly visible perimeatal or meatal HPV infection should undergo urethroscopy and that voided urine cytology is not a reliable or cost-effective test for the detection of visible intraurethral disease.

Condylomata Acuminata↗

Response to interferon treatment decreases with epidermal dedifferentiation in condylomas.

After interferon (IFN) treatment of patients with condyloma acuminatum, groups clinically proven to be responders or nonresponders were selected, and cellular parameters that might influence the clinical response were studied in pretreatment biopsies by reverse transcription polymerase chain reaction (RT-PCR). The nonresponders were found to express higher amounts of cellular proliferative markers, such as proliferating cell nuclear antigen (PCNA), cyclin A, and cdc 2 kinase, but lower levels of growth suppressor genes (TGF-beta 1, TGF-beta 2 and p53) before IFN treatment. The responders retained the epidermal keratinization, except for some signs of hyperproliferation (K6, K16 cytokeratins). In addition, the nonresponders showed a shift in the keratinization pattern to a mucosal or fetal type, as evidenced by high expression of the K18, K6, K16 and K13 cytokeratins but decreased K5, K14 and K10 levels before treatment. The expression of the human papillomavirus (HPV) genes is consistent with these differentiation patterns. The crucial conclusion to be drawn from this study is that those condylomas whose pretreatment phenotype most closely resembles that of normal epidermis respond to IFN treatment, whereas those more akin to nonkeratinizing epithelia fail to respond, i.e. the resistance of condylomas to IFN treatment is correlated with dedifferentiation.

Base Sequence↗

Differential expression of HPV types 6 and 11 in condylomas and cervical preneoplastic lesions.

Tumor biopsies from exophytic and flat condylomas at different locations on the genital epithelium (10 cases) and in cervical intraepithelial neoplasia (CIN) grades 1-2 (6 cases) were analysed for HPV types 6 and 11 DNA and RNA. The presence of mRNA species which could encode the E6, E7, E1M, E2, E2C, E4, E5 and L1 proteins was determined using the RNA polymerase chain reaction (PCR) technique with primers that flank previously mapped or predicted splice sites. The state of the viral DNA in the tumor biopsies was established by Southern blot analysis. We could detect the various mRNA species in biopsies from condylomas associated with both HPV types. The size of the RNA PCR products were in agreement with the previously mapped splice sites of mRNAs recovered from an experimental condyloma induced by HPV11. The major viral transcript encoding the E1i--E4 protein was detected in all the tumor biopsies. From the rare transcripts the rate of detection of mRNA species encoding the E1M, E2C proteins was the highest. In 2 of 6 CIN biopsies analysed only the major viral transcript was detected. The overall results of this study suggest that early gene products of HPV types 6 and 11 may be important in the induction of cellular proliferation and condylamatous differentiation but these possibly may not be required for the development of the HPV-associated cervical neoplasia.

Base Sequence↗

Treating genital condyloma during pregnancy with the carbon dioxide laser.

The therapeutic effectiveness of the carbon dioxide laser was evaluated in 43 pregnant women with extensive urogenital and anal condylomas. All patients received one treatment and were followed up for an average of 9 months after delivery. Laser failures (persistent disease) and recurrences (new disease) were stratified according to the location of the lesions and the gestational age of the patients. The overall failure rate was 5%; 6% of the women with multiple sites involved had persistent disease but none of the lesions confined to the vulva persisted after laser treatment. The recurrence rate was 14%; 33% and 17% of the patients treated during the first and second trimesters, respectively, had recurrent disease irrespective of the areas involved. Recurrences were not observed in women treated during the third trimester of pregnancy. Laser vaporization of genital condylomas was not associated with perioperative or postoperative bleeding or infections. Laser therapy is an attractive means of treating urogenital and anal condylomas during pregnancy and is most effective near term.

Anus Neoplasms↗

Assessing child abuse in childhood condyloma acuminatum.

Adults with condyloma acuminatum are considered to have a sexually transmitted disease. Childhood condyloma acuminatum may often, but not always, be a manifestation of sexual abuse. We provide a checklist of criteria for suspecting child abuse. We recommend that if clinicians find a "yes" response on this checklist when caring for a child with condyloma acuminatum, consultation with local child protective services (CPS) be deemed mandatory.

Child↗

Imiquimod is highly effective for extensive, hyperproliferative condyloma in children.

We describe a dramatic response to imiquimod of long-lasting, highly proliferative extensive perianal condylomas involving the anal canal in a 19-month-old girl. Her mother was free of condyloma and allegedly had no human papillomavirus (HPV) infection during pregnancy. There was no evidence of sexual abuse. Application of 5% imiquimod cream to the child every other day for 3 weeks resulted in almost complete resolution of the warts, with total clearance within another 2 weeks. The inflammatory reaction was moderate. Since there is still discussion of whether imiquimod may be prescribed for small children, this case of very extensive condyloma provides evidence that the compound is safe and highly effective.

Administration, Topical↗

Condyloma acuminatum in the oral cavity: four cases and a review.

The number of reported cases of condyloma acuminatum has increased rapidly in recent years. While the viral etiology of these lesions has been established, differentiation from other papular growths is often difficult. Reports of condyloma acuminatum lesions in the oral cavity are appearing more frequently, although they still are sparse. Four cases of oral condyloma are described, and the English-language literature on other such cases is reviewed. Presumably, as the incidence of this type of infection continues to increase, oral condylomata will become a commoner diagnosis. Physicians and dentists should be aware of the necessity of recognizing wart-like eruptions in and around the oral cavity.

Adult↗

The effects of resin of podophyllin on condyloma acuminatum.

The effects of resin of podophyllin on lesions of condyloma acuminatum have posed problems to pathologists who sought to differentiate them histologically from squamous cell carcinoma in situ. The most striking histologic changes in lesions of condyloma acuminatum following application of resin of podophyllin occur within the first 48 hours. They are pallor of the epidermis secondary to both intracellular and intercellular edema, numerous necrotic keratinocytes in the lower half of the epidermis, and a marked increase in the number of mitotic figures there. Within the edematous papillary dermis, there is a scattered infiltrate of lymphocytes, histiocytes, and neutrophils. The absence of nuclear atypia, multinucleated keratinocytes, and dyskeratotic cells, and the presence of the orderly sequence of maturation of keratinocytes within the epidermis permit histologic differentiation of podophyllin-treated condyloma acuminatum from true squamous-cell carcinoma in situ. The acute histologic changes induced by podophyllin begin to wane by 72 hours after the resin has been applied. At this time, necrotic keratinocytes are found mostly within the upper portion of the epidermis and few mitotic figures are seen. By 1 week after application of podophyllin there are virtually no histologic abnormalities within the epidermis.

Adult↗

Genital condyloma virus infection following pelvic radiation therapy: report of seven cases.

Six women who underwent radiation therapy for gynecologic malignancies demonstrated cytologic evidence of condyloma virus infection 2 or more years following radiation. Histologic confirmation was obtained in two of the cases. A seventh patient developed in situ and invasive squamous cell carcinoma in a vulvar condyloma acuminatum following radiation therapy for Hodgkin's disease. This venereal infection is found most frequently in sexually active younger women (average age, 27 years). It is felt that depressed cell-mediated immunity consequent to the radiation therapy allowed the development of this infection in the older patients described in this report. The evolution of invasive squamous cell carcinoma in the condyloma acuminatum may indicate a possible oncogenic or cocarcinogenic effect of the virus. The immunologic responses to infection caused by the human papillomavirus group are discussed, as well as its potential for malignant transformation.

Adenocarcinoma↗

Risk factors for condyloma acuminatum in women.

We interviewed 49 women who had a history of condyloma acuminatum and 196 age-matched controls. For women who had ever smoked, the risk of developing condyloma was 3.7 times that of women who had never smoked (95% confidence interval, 1.8-7.6). The relative risk associated with long-term use (five or more years) of oral contraceptives was 9.8 (95% confidence interval, 1.5-65.6). Condyloma acuminatum is caused by infection with human papilloma virus (HPV), usually types 6 or 11. Infection with HPV, most commonly of other types, is associated with an increased risk of cervical neoplasia. If smoking and oral contraceptives increase the risk of infection with these other types of HPV as they do with types 6 and 11, this factor could be the means by which smoking and long-term use of oral contraceptives increase the incidence of cervical neoplasia.

Adolescent↗

Infrared coagulation in the treatment of condyloma acuminata in the female genital tract.

An infrared contact coagulator was used for the treatment of genital condyloma acuminata in 89 women. After direct application to the condyloma, the device produces a precisely adjustable tissue necrosis without tissue adhesion. Of the 89 women, 74 returned for scheduled follow-up visits after one, three, and six months. Treatment failure, i.e., recurrence of warts in a treated area, was seen in 13 (10.8%) of 120 treated areas, or in 13 (17.6%) of 74 patients. No complications were observed. The physical working principle of infrared coagulation as well as the results in treatment of condyloma are the same as those of the CO2 laser, but the equipment is cheaper, safer, and more easily handled. It can be used in out-patient departments of clinical and general practices.

Adolescent↗

Genital condylomas in immunosuppressed women: a therapeutic challenge.

Of 30 immunosuppressed women with genital condylomas, 20 (67%) had associated neoplasia of the lower genital tract. We retrospectively studied 11 patients with flat condylomas confined to the cervix; all lesions were eradicated by conventional therapy. Three patients studied retrospectively and 16 studied prospectively had condylomatous lesions involving several sites within the lower genital tract. These lesions were unusually resistant to various treatment methods. Maintenance therapy with 5-fluorouracil (5-FU) cream resulted in a significantly higher control rate (6/7 patients, 86%) than could be achieved otherwise (2/9 patients, 22%; P less than .025). We conclude that ablative therapy by surgery or topical chemical agents followed by maintenance therapy with 5-FU cream may be the treatment of choice for condylomas and other human papillomavirus-associated lesions of the lower genital tract in immunosuppressed women.

Adult↗