Human papillomaviruses associated with cervical intraepithelial neoplasia. Great diversity and distinct distribution in low- and high-grade lesions.

All together, 30 genital human papillomavirus (HPV) types have been characterized so far. To evaluate the importance of HPV diversity in associated cervical diseases, we analyzed 188 biopsy specimens obtained from patients with a recent diagnosis of cervical HPV infection or intraepithelial neoplasia (CIN). Of these 188 specimens, 116 were classified as low-grade CIN (48 cases), high-grade CIN (53 cases), condylomata acuminata (10 cases), flat condylomas (five cases). Seventy-two specimens were considered nondiagnostic. Using probes specific for 18 genital HPV types, HPV DNA sequences were detected by Southern blot hybridization in 100 lesions and 21 nondiagnostic specimens. When further analyzed by the polymerase chain reaction, eight HPV-negative biopsy specimens, four CIN, and four nondiagnostic specimens were positive. Of the 129 positive biopsy specimens, 92 contained at least one of 18 known HPV types and 37 HPV that have not yet been identified. Nine specimens had more than one type. Thirteen HPV types were identified in CIN. The detection rate of HPV 16 increased from 21% in low-grade CIN to 57% in high-grade CIN. HPV 18 was detected in only 3% of CIN; HPV 31, 33, and 35 were found in 8%. HPV 30, 39, 45, 51, 52, 56, 58, and 61 were detected in 44% of low-grade CIN but in only 8% of high-grade CIN. Unidentified HPV were detected in about 25% of low-grade and high-grade CIN. Fifty-seven CIN positive for at least one HPV type were further analyzed by in situ hybridization. Thirty-five (65%) biopsy specimens were positive, including 21 of 24 low-grade CIN and 14 of 33 high-grade CIN. Ten of the 13 previously identified HPV types were detected. Thus, CIN represents an heterogeneous disease from a virologic viewpoint. This fact could explain their variable clinical evolution.

HPV infection and disease in men.

Penile HPV infection and disease are very common in sexually active men, and may be manifest in many forms. Treatment of clinically detectable lesions is advisable not only to relieve symptoms but also to prevent the spread of HPV infection to new sexual partners. Treatment of subclinical disease is more controversial but also may be advisable in some cases given the evidence that these lesions may also harbor infectious virus. In addition, subclinical disease may demonstrate intraepithelial neoplasia, which if left untreated may progress to invasive cancer in a small number of cases. Anal HPV infection and ASIL are very common in high-risk homosexual and bisexual men, particularly among those who are HIV positive. Parallels with cervical HPV infection and disease suggest that anal HSIL may be precancerous, and indeed anal cancer may be as common or more common in this high-risk group as cervical cancer is in women. Further studies are needed to elucidate the natural history of ASIL, the role of immunosuppression in progression to invasive cancer, optimal diagnostic methods, and optimal treatment regimens. Like cervical cancer, anal cancer may be a preventable disease, and implementation of a well-targeted screening program similar to that in place for cervical disease should be considered in the future when appropriate supporting data become available.

Accuracy of thin-layer cytology in patients undergoing cervical cone biopsy.

OBJECTIVE: To compare the accuracy of thin-layer cytology with Autocyte PREP (TriPath Imaging Inc., Burlington, North Carolina, U.S.A.) with conventional smears in 500 women undergoing cervical cone biopsy. STUDY DESIGN: The study was performed among 500 consecutive women presenting for cone biopsy for high grade cervical intraepithelial neoplasia (CIN) on biopsy in 350 (70%) and discrepant cytology/colpohistology in 150 (30%). Before performing a cone biopsy, two cervical samples were collected for conventional smears and thin-layer cytologic slides, with randomization of the order. Conventional smears were stained and diagnosed at Pasteur Cerba, while thin-layer cytologic slides were processed at a local TriPath office (Meylan, France) and sent in a masked fashion for screening at Pasteur Cerba. Any slides initially read as normal were reviewed again and reported without knowledge of the other cytologic or cone biopsy data. The final cytologic diagnoses for the two methods were compared with histopathology of the cone biopsy. RESULTS: The conventional smear was unsatisfactory in 58 (11.6%) of cases, while there were 4 (0.8%) unsatisfactory thin-layer cytologic slides (P < .001). Endocervical cells were missing from 31 (6.2%) of conventional smears and 34 (6.8%) of thin-layer cytologic slides. For the pooled data, sensitivities of conventional smear and thin layer for detecting high grade CIN (0.82% and 0.86%, respectively) were similar as were specificities (0.40% and 0.43%, respectively). When first samples were compared, the sensitivities of the conventional smear and thin layer for high grade CIN were 0.79% and 0.89%, respectively (P = .02), with corresponding specificities of 0.41% and 0.36% (P < .01). CONCLUSION: When controlled for sample order, the sensitivity of thin-layer cytology for detecting high grade CIN was significantly higher than that of conventional smears in patients with previous abnormal cytology, but at the expense of specificity.

[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.

[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.

[Possibilities and limitations of the acetic acid test in the identification of vulvar papillomavirus lesions. A colposcopic, histologic and virologic study]. / Apports et limites du test à l'acide acétique dans l'identification des lésions vulvaires à papillomavirus. Etude colposcopique, histologique et virologique.

42 subclinical HPV related vulvar lesions have been studied by Southern Blot Hybridization and histological samplings. 15 women had normal Pap smears. Cervical intraepithelial neoplasia was present in 24 other women, 15 of them had HPV on Southern Blots. Macular or papular areas on the vulva were strongly correlated with HPV infection, since 6 out 9 of them harboured HPV 16, 42 or X. Histologically, flat condyloma was present in 6 cases. However, 33 nonspecific acetowhite reactions of the vulva were free of HPV. It is therefore important to recognize such aspects on colposcopical examination of the vulva to avoid unnecessary treatment.

[Treatment of genital Papillomavirus lesions]. / Traitement des lésions génitales à Papillomavirus.

Genital Papillomavirus infection has now reached epidemic size. Several techniques may be used to treat genital condylomas, but none of them is 100 percent effective. At the first consultation for external genital condylomas, the choice of treatment is determined by the size, location, number and histology of the lesions. Typical condyloma acuminata that are present in small number and have a less than 5 mm base of implantation are treated by cryotherapy or trichloracetic acid. Podophyllin should be reserved for patients with diffuse lesions. When one or several lesions do not regress after 3 to 4 weeks of treatment, surgical procedures (electrocautery, CO2 laser) must preferably be used. Condylomas that have a base of implantation wider than 5 mm are directly destroyed by surgical excision, as are dysplastic lesions. Post-treatment cure of external genital lesions must be confirmed by a negative acetic acid test. Patients should be advised to utilize condoms throughout the duration of treatment.

[Male genital lesions caused by papillomaviruses. Importance of colposcopy]. / Lésions génitales masculines à papillomavirus. Intérêt de la colposcopie.

Ten years after the description of cervical flat condyloma, it is now admitted that Human Papillomaviruses (HPVs) type 6 and 11 are responsible for condylomata acuminata and typical flat condyloma of the uterine cervix. HPV DNA type 16 and, less frequently, 18, 33 and other as yet uncharacterized HPV types (G. Orth, personal communication), are found in the majority of Cervical Intraepithelial Neoplasia (CIN), Vulvar Intraepithelial Neoplasia (VIN) and cervical and vulvar invasive cancers. Since HPVs are sexually transmissible, recent interest has focused on the "male factor". Clinically detectable lesions of male genitalia are condylomata acuminata, bowenoid papulosis and flat condyloma-like papules. The aim of our study was the colposcopical screening, recently suggested, of different groups of male patients in order to detect HPV-related lesions and the description of the colposcopical features of subclinical HPV-related lesions, since most of them have never been reported, to our knowledge, in the literature. A total of 114 men were examined. Among them, 18 presented clinically detected recalcitrant condylomata acuminata, 28 had been treated for the same pathology 1 to 5 days earlier and were clinically free of lesions, 46 were sexual partners of women with cervical atypia (flat condyloma and/or CIN) and 22 had a clinical diagnosis of genital infection without HPV-related lesions. A careful examination of external genitalia was performed. Then all patients underwent penile colposcopy before and after application of 5 p. 100 acetic acid. Selected biopsies were performed in all lesions which were clinically and colposcopically different from classic warts. Colpophotographs were taken in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)

[Value of therapeutic circumcision in diffuse condylomata acuminata]. / Intéret de la circoncision thérapeutique dans la condylomatose diffuse.

Therapeutical circumcision (posthectomy) in nine patients presenting with diffuse penile warts. CO2 laser circumcision resulted in a 100 p. 100 cure rate after a 3-month follow-up in patients with diffuse warts of recent onset, and a 75 p. 100 cure rate in patients with recalcitrant warts.

[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.

[Cancer of the uterine cervix: epidemiology and virology]. / Cancer du col de l'utérus: épidémiologie et virologie.

Numerous epidemiological studies have made it possible to isolate groups of women at risk or developing an epidermoid carcinoma of the uterine cervix. Among the factors studied, age at the time of the first sexual intercourse and number of male partners were found to be statistically significant factors. No study has yet proved that smegma facilitates cancer and that circumcision may prevent its occurrence. However, the importance of the "male factor" has been enhanced by many studies suggesting the possibility of an oncogenic factor transmissible by sexual intercourse. Several data suggest that some types of human papillomavirus are the necessary, if not sufficient, factors of cervical oncogenesis. Some types of herpes virus, notably HPV 16, can be identified in the majority of invasive cancers and their direct precursors: intraepithelial neoplasias. The carcinogenic role of papillomaviruses in animals ans in laboratory experiments supports the theory that these sexually transmissible viruses are involved in the origin of epidermoid cervical carcinoma.