Penile intraepithelial neoplasia. Specific clinical features correlate with histologic and virologic findings.

BACKGROUND: To evaluate the existence of the morphologic features specific for penile intraepithelial neoplasia (PIN), 1000 male sexual partners of women with genital condyloma or intraepithelial neoplasia were studied. METHODS: Ninety-two patients who presented with lesions suggesting intraepithelial neoplasia (pigmented or leukoplastic papules, keratinized condylomata, or erythroplastic macules) underwent biopsy for histologic and virologic studies. RESULTS: Histologic results showed penile intraepithelial neoplasia in 93% of the specimens. Human papillomavirus (HPV) DNA from potentially oncogenic papillomaviruses was detected in 75% of patients with Grade I PIN, in 93% of patients with Grade II PIN, and in all patients with Grade III PIN: Uncircumcised and circumcised men showed the same rate (52% vs. 45%; odds ratio [OR] = 1.3; 95% confidence interval, 0.97-1.73) of HPV-associated lesions, whereas the rate of PIN was significantly higher in uncircumcised men than in circumcised men (10% vs. 6%; OR = 1.77; 95% confidence interval, 1.02-3.07). The mean age of patients with Grade III PIN was 7 years older then the mean age of patients with Grade I PIN, which suggests a step progression similar to that of cervical intraepithelial neoplasia. CONCLUSION: Morphology seems to be a specific-enough indicator of PIN. More data are needed to determine whether treatment of PIN may contribute to preventing cervical or penile cancer. If so, the morphologic criteria here described will be clinically useful.

[Genital herpes simplex virus infection among men screened for genital papillomavirus]. / L'infection génitale par les herpès simplex virus parmi des hommes consultant pour un dépistage des papillomavirus génitaux.

OBJECTIVE: Our aim was to assess the frequency of herpetic genital infection (HSV) among men attending a human papillomavirus (HPV) screening centre. Clinical screening of a herpetic lesion was completed with biological detection of HSV by cell culture and by polymerase chain reaction (PCR). We also evaluated the role of the male viral factor on the female partners. METHOD: We performed a genital examination by colposcopy of 135 men whose female partners presented an HPV genital infection. The HPV lesions detected underwent biopsy by Southern blot viral analysis. The lesions which clinically appeared to be caused by HSV were removed for HSV detection and typing by cell culture and by PCR. Sperm was collected for viral detection by cell culture and PCR was collected for viral detection by cell culture and PCR from patients presenting a herpetic type urethral symptomatology. RESULTS: Peniscopy detected HPV lesions in 46 p. 100 of the men, in 88 p. 100 of cases in the balano-preputial zone and in 82 p. 100 of cases their morphology was exophytic. The other areas were in 14.5 p. 100 of cases urethral and 9 p. 100 anal. We detected a dysplasic lesion in 6 p. 100 of cases. In 74 p. 100 of cases molecular hybridization by Southern detected 6/11/42 type HPV and in 6.4 p. 100 of cases HPV 16. Clinical examination revealed the presence of genital herpetic infection in 15.5 p. 100 of cases, of these 76 p. 100 were preputial and 24 p. 100 meato-urethral. PCR detected HSV-2 in 88 p. 100 of the preputial lesions and in 86 p. 100 of the spermatic ejaculates from the meato-urethral lesions. The chi 2 test showed that no link exists between a herpetic genital infection and the presence of an HPV lesion, but that the risk is greater (OR = 2.15; IC 95 p. 100 = 0.84-5.49). We also observed that 50 p. 100 of the female partners of men with both HPV+HSV infections had high grade cervical lesions. CONCLUSION: This study shows that clinical examination in an HPV screening centre enabled detection of clinical HSV in 15.5 p. 100 of cases as opposed to 17 p. 100 biologically. Thus the good clinical-virological correlation shows that clinical criteria remain the principal elements for detecting viral genital infections, it therefore appears advantageous to only use the new HSV identification techniques for targeted detection. Also, herpetic genital infection is independent of human papillomavirus infection. When screening for HPV, herpetic genital infection should be taken into account as we have observed that the female partners of men with both HPV + HSV are at greater risk of presenting high grade cervical lesions.

[Male genital examination: the usefulness of penis endoscopy and the acetic acid test for the detection of papillomavirus lesions]. / Examen génital masculin: l'utilité de la péniscopie et du test à l'acid acétique pour le dépistage des lésions à papillomavirus.

This study was based on 2,400 genital examinations performed by means of the acetic acid test looking for human papillomavirus (HPV) lesions in the male partners of women with HPV genital lesions. These peniscopies demonstrated HPV lesions in 56% of the men examined. In 109 cases, histological and virological examination revealed that 30% of them had areas of intraepithelial neoplasia of the penis, associated with potentially oncogenic papillomavirus infection. The value of this examination is to detect HPV lesions and, in particular, dysplastic lesions. The treatment of these lesions appears to allow a reduction in the incidence of recurrence of HPV lesions in women after treatment.

Correlative study of human papillomavirus DNA, histopathology and morphometry in cervical condyloma and intraepithelial neoplasia.

This study includes 28 intraepithelial squamous lesions of the cervix associated with human papillomavirus (HPV) DNA sequences detected by the Southern blot technique. Objective analyses of the histologic features by morphometric parameters and mitotic index have demonstrated that lesions of HPV types 6 and 11 can be distinguished from types 16, 18, and 33 by stepwise discriminant functions. The latter lesions have higher mitotic and cellularity indexes and greater nuclear atypia than the former, supporting a greater degree of epithelial proliferation and abnormality seen in association with HPV types 16/18/33.

Human papilloma viruses and cervical intraepithelial neoplasia: the role of colposcopy.

To evaluate the reliability of colposcopy for distinguishing flat condyloma from cervical intraepithelial neoplasia (CIN), 211 patients with abnormal cytology, colposcopical evidence of an atypical transformation zone (ATZ), and a histological diagnosis of flat condyloma or CIN were studied. Colposcopic evidence of surface abnormalities, the presence of satellite lesions, and an irregular Lugol's uptake were tentatively considered to be features of condyloma. Histologically, koilocytotic lesions with a disorganized cytologically atypical basal/parabasal layer and with atypical mitotic figures (AMFs) were considered to be CIN cases, and designated as CIN with koilocytosis (CIN K). At least two colposcopic features of condyloma found in 98 of 99 flat condylomas, were also found in 89 of 112 CINs. When colposcopic features were matched with histology for every directed biopsy site, they correlated strongly with koilocytosis, regardless of the degree of atypia in the lesion. Moreover, these features often occurred at the periphery of poorly differentiated or undifferentiated, high grade CINs, in areas histologically indistinguishable from flat condyloma. Thus, colposcopic features are not of predictive value in distinguishing flat condyloma from CIN, do not show correspondence to the lesional degree of atypia and cannot be fully related to the biological characteristics of the cervices in which they are found. These findings confirm that colposcopy cannot be considered to be a diagnostic method.

[Comparative epidemiologic study of 120 patients with condylomatous lesions and 120 control patients]. / Etude épidémiologique comparative entre 120 patientes atteintes de lésion condylomateuse et 120 patientes témoins.

The authors compared 120 women who had condylomata with 120 controls. The patients were more frequently single or divorced than the controls. Age at first sexual intercourse was the same in the patients and in the controls, but the total number of sexual partners was higher in the patients than in the controls. The age at first pregnancy was 24 years in the patients and 28 in the controls. About equal numbers of genital infections were found in the history of the controls as in the patients. On the other hand some specific urogenital infections were more frequent in the patients. Chlamydia diagnosed by a positive level at 1/64 in the serum test occurred in 21.4 per cent of patients and 5.5 per cent of controls.

[Histological aspects of lesions of the cervix uteri correlated with different types of human papillomavirus]. / Aspects histologiques des lésions du col uterin correlés aux différents types de papillomavirus humains.

Cervical biopsies from 66 women presenting an abnormal smear, with HPV related features were studied and histologic features were correlated to the HPV type, as determined by molecular hybridisation studies. HPV DNA sequences were evidenced in 13 of 19 lesions corresponding to exophytic or flat condyloma (HPV type 16 in seven cases, HPV type 11 in four cases, as yet uncharacterized HPV types, HPV X, in two cases). Fourty biopsies were histologically interpreted as CIN, on the basis of atypical mitotic figures (AMF) and/or basal-parabasal cell atypia. HPV type 16 was evidenced in 20 cases (3 cases of double infection: HPV types 16 and 18, HPV types 16 and 33, HPV types 16 and X). In 10 other cases, HPV DNA sequences corresponding to HPV type 11 (one case), HPV 18 (one case) and HPV X (8 cases) were evidenced. In this study, potentially oncogenic HPV types (HPV 16, HPV 18, HPV 33) have been found only in CIN lesions defined on the presence of AMFs and/or basal-parabasal cells atypia. These histologic criteria seem to allow a distinction between low and high risk cervical lesions.

[Papillomavirus infection and cervical intraepithelial neoplasia (CIN). Study of CINIII in 2 series of conization and hysterectomies (1957-1968 and 1981-1983)]. / Infection à papillomavirus et néoplasie cervicale utérine intra-épithéliale (CIN). Etude des CINIII dans deux séries de conisations et hystérectomies (1957-1968 et 1981-1983).

At the Institute of Pathology and Applied Cytology, 619 cases of conization or hysterectomies for CIS had been reviewed, through the study of 6,439 slides: 263 cases from the years 1957-1968, 287 cases from the years 1981-1983, have been studied. In the 1957-1968 group, a condylomatous lesion was associated with CINIII/CIS in 60% and in 79% in the 1981-1983 group. The relationship between the condylomatous lesions and the CIS, the grade of these lesions and the mean age of the patients had been examined. In the both groups, the HPV signs had been more frequently discovered in the younger women. But a difference of 4 years was found between the patients with CINIII without any sign of HPV infection and those with a CINIII/CIS associated with a condyloma. These data support the hypothesis of a lessening and a later disappearance of the HPV signs when the neoplasias become more severe. In both groups, the relationship between the signs of HPV infection and the grade of the cervical epithelial atypias are exactly the same. These lesions, more often extended, with a transitional passage between CIN with HPV cytopathological effects and CIS, comfort the hypothesis of a straight relationship between HPV infection and carcinoma of the cervix.

[In situ cancer of the cervix and papillomavirus. Study of lll cases of conization]. / Cancer in situ du col et papillomavirus. Etude de 111 conisations.

A series of 111 cervical conization specimens from patients with carcinoma in situ (CIS) have been examined by the authors in order to point out the real incidence of condylomatous lesions and their different aspects. The histological criteria of condyloma and cervical intra-epithelial neoplasia (dysplasia and CIS) are recalled, and relationships between them are discussed. Koïlocytes have been observed in 77.5% of CIS examined. Different localisations of condylomatous aspects as regards dysplastic and neoplastic lesions are described and discussed. The histological pattern defined as CIN III with incomplete signs of condylomatous lesion, is significantly associated to flat condyloma (72.7% of cases). Morphological and biological border between condyloma and CIN seems to be not clean; therefore the authors stress on the careful screening, treatment and follow-up of this patients.

[Condylomatous lesions of the uterine cervix: their course in 2466 patients]. / Lésions condylomateuses du col utérin: évolution chez 2 466 patientes.

2466 women with cervical condylomatous lesions out of the general consulting (0.7%) have been followed by the authors. The cytological and histological criteria of these lesions and the detection of the viral antigen by immunoperoxidase (positive in only about 50% of the cases), are recalled. The flat condylomas are often associated with dysplasia (CIN I, II, III). The condylomas appear in women before the age of 20. These cases increased in number between the ages of 25 to 30 and stayed high until 35. The number of condylomas associated with CIN II have their maximum between 36 and 38 years of age and decrease afterwards to age 48. The graphic is the same for CIN III. The evolution of these condylomatous lesions studied during 42 months, shows that in 1269 women with condyloma and nuclear atypia, regression occurred in 53 per cent, persistence in 37 per cent and aggravation in 10 per cent of the cases. In 762 women with CIN II, regression appeared in 39 per cent, persistence in 44 per cent and aggravation in 17 per cent of cases. In a group of 764 closely followed women, regression and aggravation in CIN I and II appeared between the 3rd and the 6th months of follow-up. Condyloma associated with CIN III were not observed after the 3rd month. Recurrence appeared however in 55 cases after insufficient ablation. Lastly, the histogenesis of these lesions and the relationship between the viral action and the host are discussed.

[Condylomas, cervical dysplasias and carcinoma of the cervix (author's transl)]. / Condylomes, dysplasies et carcinomes intra-épithéliaux du col utérin.

Because the greater number of viral cervical lesions, the authors recall their cytological and pathological pictures. In 30% of the causes, they have observed relations between flat condylomas and cervical severe dysplasias and carcinoma in situ. But in these last lesions, the cytological characters of the viral infestations are not visuable. The relationship between condyloma and carcinoma in situ is explained by the virus modifications on the germinative cells genoma which enhance great multiplication of these cells and inhibit the epidermoid differentiation. When the virus are not very active, or the host responses sufficient, the cell differentiation and maturation permit the replication of the virus and its appearance in the cytoplasm of the superficial cells. The authors stress on the complete destruction of the viral cervical lesions and the later control of the cervix.