Oral contraceptives and human papillomavirus infection in cervical intraepithelial neoplasia

Summary We report about 142 patients from whom colposcopically directed cervical punch biopsies were taken which showed condylomatous lesions with or without cervical intraepithelial neoplasia (CIN). Fiftysix (39.4%) of these women used oral contraceptives (OC) for at least two years before examination. We used DNA in situ hybridization on all biopsies for detection of human papillomavirus (HPV)-DNA. Among OC users a significant trend towards higher HPV infection rates in high grade CIN (odds ratio 2.9,P<0.05) was found, whereas non-users of oral contraceptives had the highest HPV infection rate in condylomatous lesions without CIN (odds ratio 0.5,P<0.05). Thus in OC users HPV infection was about 24 times more likely in CIN III as in condyloma, whilest among non-users the trend was the other way round (7-fold likelyhood of HPV positivity in condyloma compared to CIN III). Other known risk factors for cervical carcinoma did not influence HPV infection rates in either group.     

Condyloma and intraepithelial cervical neoplasms. Epidemiological contribution to their interpretation

The frequency of condylomatous lesions and of intraepithelial neoplasms of the cervix (CIN) and their possible association in the female population of Trieste have been evaluated. The analysis was carried out on the basis of biopsy samples of the uterine cervix examined at the Department of Pathological Anatomy and Histology of the University of Trieste in the period between 1-1-1983 and 31-12-1987. In the five-year period considered, 272 papillomavirus lesions and 451 cases of CIN were diagnosed. The condylomatous infections were associated with CIN in 48% of cases. An association with CIN 1-2 was encountered in 32.4% and with CIN 3 in 15.4% of cases. CIN 1-2 was associated with condylomatous lesions in 35.2% and CIN 3 in 20.9%. The average age of patients with cervical condyloma was 29.5 years, while that of patients suffering from CIN 1-2 and CIN 3 was respectively 31.9 and 38.7 years. The patients who presented the association between the two pathologies were younger than those suffering from CIN alone: the average age was in fact 28.7 years among women suffering from CIN 1-2 and viral infection and 35.7 in those with condyloma and CIN 3. In the five years examined, a marked tendency was encountered towards an increase in both pathologies examined and this was seen exclusively in the associated lesions.     

Spatula/cytobrush vs. spatula/cotton swab detection of cervical condylomatous lesions

Human papillomavirus is widely implicated as a primary etiologic factor in cervical carcinoma. This study compared the sampling accuracy of the modified Ayre spatula/Zelsmyr cytobrush versus the modified Ayre spatula/cotton swab in the detection of cervical lesions with koilocytotic features. The histologic categories consisted of koilocytotic lesions (flat condylomas) with minimal cellular atypia and cervical intraepithelial neoplasia (CIN) I, II and III with surface koilocytes showing cellular atypia (atypical koilocytosis). Using the spatula/cytobrush there was 88% concurrence (118/134 cases) between the cytologic/histologic diagnosis of flat condyloma and CIN with atypical koilocytosis. Using the spatula/swab there was a cytologic/histologic concurrence of 68% (71/104 cases). Statistical analysis confirmed the difference between the two techniques to be significant. In addition, a higher percentage of CIN II and III lesions with koilocytotic features was detected with the spatula/cytobrush--54% (19/35 cases) as compared to 30% (14/46 cases) for the spatula/swab. The results of this study support the use of the spatula/cytobrush in the detection of cervical lesions with koilocytotic features.     

p53 Polymorphism (codon-72) has no correlation with the development and the clinical features of cervical cancer

Abstract. Nishikawa A, Fujimoto T, Akutagawa N, Iwasaki M, Takeuchi M, Fujinaga K, Kudo R. p53 polymorphism (codon-72) has no correlation with the development and the clinical features of cervical cancer.
Recent analysis of the codon-72 polymorphism of the p53 gene, the allele encoding proline or arginine, suggested that the homozygous Arg/Arg genotype is a significant risk factor for cervical cancer associated with human papillomavirus (HPV). We investigated the polymorphism of p53 in cervical condylomas, cervical intraepithelial neoplasias (CINs), and cervical cancers, evaluating clinical implications of the polymorphism of p53 in development of cervical neoplasms. DNA from 87 cervical cancer tissues, 28 CIN tissues, and seven cervical condyloma tissues were examined for the presence of HPV DNA by the consensus PCR method and the p53 polymorphism was analyzed by PCR using an allele-specific primer. The frequencies of p53Pro, p53Arg, and p53 Pro/Arg were 14.3%, 57.1%, and 28.6% in condyloma patients; 21.4%, 39.3%, and 35.7% in CIN patients; and 10.3%, 44.8%, and 42.5% in cervical cancer patients, respectively. No statistically significant differences in the distribution of p53 genotypes were found among the patients with these diseases, regardless of HPV status. Furthermore, there was no clear correlation between the polymorphism of p53 and age, histopathologic type, clinical stage, or lymph node metastasis. Nor was there any evidence of a correlation between the p53 genotype and the outcome for patients with HPV-positive uterine cervical cancer.     

In situ cancer of the cervix and papillomavirus. Study of lll cases of conization

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. Ko?locytes 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.     

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.     

The evaluation of proliferative activity in CIN III and microinvasive cervical cancer and its role in recurrence

OBJECTIVE: To evaluate the proliferation activity in CIN III lesions and Ia1 carcinoma according to the risk of recurrence. STUDY DESIGN: The proliferation markers PCNA (proliferating cell nuclear antigen) and mitotic index were studied in 75 patients with CIN III and in 20 patients with an Ia1 squamous carcinoma of the cervix by staining representative tissue sections for the PCNA and assessing the mitotic index. Associations between the studied proliferation markers and various histopathologic characteristics as well as recurrence were assessed. RESULTS: Three groups of PCNA were constituted: <20, 20--40, > OR =40% positive tumour nuclei, which contained, respectively, 45 (47%), 29 (31%), and 21 (22%) patients. Microinvasive carcinomas have a higher proliferation activity than CIN III (PCNA P=0.005; mitotic index P=0.094). For CIN III, there was a significantly lower risk for recurrence in the group with lower mitotic activity, compared to the group with higher mitotic activity (Kaplan-Meier: log-rank testing P=0.044). Significance was, however, not reached for the different PCNA categories (Kaplan-Meier, log-rank test P=0.068). Multiple regression analysis showed that in our population of CIN III lesions, only age of diagnosis and treatment modality were relevant (independent) prognostic indicators for recurrence. CONCLUSIONS: In CIN III lesions there is evidence for an association between proliferation activity and the risk of recurrence. The observed crude association weakens when adjusting for age at diagnosis and treatment modality. Apparently this feature is associated with more aggressive biological behaviour and could be used to identify women who are at higher risk of recurrence.     

Detection of human papillomavirus DNA in human cervical lesions by tissue in situ nucleic acid hybridization

Cervical cancer is one of the most common female cancers in Taiwan. Certain types of human papillomavirus (HPV) are frequently detected in the epithelial precancerous and cancerous lesions of the cervix. By the use of tissue in situ hybridization, we investigated the relationship of various types of HPV (group I, HPV-6 & 11, group II, HPV-16 & 18, group III, HPV-31, 33 & 35) with cervical condyloma, carcinoma as well as precancerous lesions. Group I HPV DNAs were mainly found in cervical condylomatous lesions (2/2) of the cervix and cervical intraepithelial neoplasia I (CIN I) (2/4), but were only occasionally found in CIN II (1/4), CIN III (1/9) or non-keratinized squamous cell carcinoma (1/15). HPV DNAs of groups II and III were mainly detected in lesions of CIN III (5/9) and invasive squamous cell carcinoma (large cell, keratinized type: 4/7; large cell, non-keratinized type: 11/15). HPV DNA sequences were invariably detectable only in the cell nuclei of condyloma or dysplastic epithelium or invasive carcinoma. However, they could not only be detected in the upper layer dysplastic cells and koilocytes but also in the well and poorly differentiated cervical cancer cells. The distribution of HPV DNA positive cells in the carcinomas fell into four different patterns: (1) upper zone and non-invasive regions of the carcinoma (11/22, 50%), (2) basal zone and invasive regions (2/22, 9%), (3) randomly scattered (7/22, 32%), and (4) extensively distributed over the whole tumor lesions (2/22, 9%). Thus, our results are consistent with a strong correlation between the presence of HPV-16, 18, 31, 33 and 35 and malignant conversion of cervical epithelial cells.     

Human papillomavirus infection and cervical neoplasia: new perspectives

This review addresses several problems associated with human papillomavirus (HPV) infection of the cervix and lower female genital tract. These include the definition of HPV infection and its distinction from HPV-associated neoplasia, the distinction of HPV infection from reactive epithelial changes induced by other infections, and the transmission of HPV infection via the male partner. The available evidence indicates that there are two distinct intraepithelial processes in the cervix associated with HPV. One is the classical condyloma and its counterpart in immature epithelium, atypical immature metaplasia. The other is intraepithelial neoplasia, which, like classical infection, may be mature [cervical intraepithelial neoplasia (CIN) with koilocytosis] or immature (high grade CIN or carcinoma in situ). Molecular hybridization studies indicate that HPVs 6 and 11 are most commonly detected in the former, whereas HPVs 16 and 18 DNA are most common in the latter and in invasive cancer. From the clinical standpoint the most important distinction is between HPV-related disease (condyloma or CIN) and reactive changes associated with other pathogens, such as Chlamydia. The former should be removed from the cervix, whereas the latter should be treated medically or followed. It is stressed that therapy should not hinge upon the histological distinction of HPV infection from neoplasia and that all lesions should be removed, by conservative means if possible. This is underscored by the fact that a high proportion of CIN lesions contain areas identical to condyloma and that lesions with deep endocervical canal involvement, including those with features suggesting condyloma, should be treated by cone biopsy to exclude the presence of invasive cancer. Histological classifications for nonneoplastic, HPV-infected, and neoplastic epithelium are proposed. The management of the male partner is still unsettled. However, a large proportion of male partners of these patients have penile lesions and should be included in diagnostic and therapeutic protocols of women with genital HPV infections or neoplasms.     

Resection margins in conization as prognostic marker for relapse in high-grade dysplasia of the uterine cervix in northern Norway: a retrospective long-term follow-up material

OBJECTIVE: The main intention of the current study was to evaluate free resection margins in cervical conization specimens as prognostic marker by investigating the statistical association between clear or unclear resection margins of cervical cones and the risk of recurrence. METHODS: In a retrospective material, 459 women with moderate (CIN II) and severe dysplasia (CIN III) were included. Fifty of the patients were diagnosed with CIN II (10.9%) and 409 with CIN III (89.1%). Cold knife conization was performed in 371 (81%) patients, the rest were treated with CO(2) laser (19%). All the patients had been treated with conization between 1980 and 1984, follow-up time being from 19 to 23 years. Mean age of the patients was 35.2 years (range 18-81 years) at operation. The histopathological material and the results of the follow-up biopsies and smears were accessible as archival material. RESULTS: A total of 379 (82.6%) patients had clear margins in the primary operation specimens, in 80 patients margins were unclear (17.4%). There were three recurrences in the CIN II group (6%) and 39 (9.5%) in the CIN III group. Further there were 42 (9.2%) relapses in the total group, 36 relapses in the cold-knife group and 6 in the laser group. When univariate analysis was performed to investigate the statistical relation between the resection margins and recurrences, there was no significant correlation (P = 0.7, P > 0.05). Nor did variables like CIN group, surgical procedure, age at disease, age at recurrence, and years till recurrence prove to be predictors of relapses. CONCLUSION: In our material, the relation between free margins and relapse was not statistically significant. According to the literature-free resection margin is not an optimal prognostic criterion for recurrence. The search for new prognostic markers for high-risk cases are important to give these patients adequate therapy and avoiding over-treatment of the low risk groups.     

人乳头状瘤病毒负荷量与子宫颈癌及其癌前病变关系的初步研究

目的　探讨人乳头状瘤病毒 (HPV)负荷量与子宫颈癌及其癌前病变的关系。方法 2 0 0 1年 12月～ 2 0 0 2年 5月 ,对山西省宫颈癌高发现场的 90 75例 35～ 5 0岁的已婚妇女 ,采用杂交捕获二代(HC Ⅱ )方法定量检测宫颈HPV DNA的含量 (以此表示宫颈HPV负荷量 )。对其中HPV DNA阳性妇女 ,随后进行阴道镜检查、宫颈多点活检和颈管诊刮术。结果　 2 0 87例HPV阳性妇女中 ,子宫颈炎14 0 2例 (6 7 2 % ) ,子宫颈癌前病变 [包括子宫颈上皮内瘤变 (CIN)Ⅰ～Ⅲ ]6 6 3例 (31 8% ) ,子宫颈浸润癌 (SCC) 2 2例 (1 1% )。急、慢性宫颈炎的HPV DNA含量分别为 10 8± 13和 15 0± 11,两者比较 ,差异无显著性 (P =0 2 5 5 ) ;不同级别子宫颈癌前病变的HPV DNA含量 ,CINⅠ为 332± 2 9,CINⅡ为 35 8±35 ,CINⅢ为 370± 31,均明显高于宫颈炎 (P =0 0 0 0 ) ,但不同级别CIN之间比较 ,差异无显著性 (P >0 0 5 ) ;SCC的HPV DNA含量为 5 93± 86 ,显著高于不同级别CIN和宫颈炎的HPV DNA含量 (P <0 0 5 ,P <0 0 1)。结论　HC Ⅱ方法是检测宫颈HPV感染的有效手段 ,HPV DNA含量随宫颈病变的严重程度而增加 ,可作为子宫颈癌的一种初筛方法。     

Immunohistochemical analysis of nm23-H1 expression in human cervical lesions

Reduced expression of the metastasis suppressor gene nm23-H1 has been previously correlated with high tumor metastatic potential and fatal clinical outcome in several types of human carcinomas. The aim of the study was to identify the expression of nm23-H1 in a variety of premalignant and malignant cervical lesions. The study comprised 106 cervical biopsies obtained from 106 women ranging in age from 23 to 68 (median 42) years. Histologic slides stained with H&E were evaluated blindly by two pathologists and a consensus diagnosis was established for each case. In addition, immunohistochemical stain was employed and a monoclonal antibody against nm23-H1 (YLEM Rome, Italy) was used. Twenty-five of the cervical biopsies showed changes of mild dysplasia (CIN I), whereas 28 demonstrated features of moderate dysplasia (CIN II) and 28 severe dysplasia (CIN III). In 25 cases infiltrating squamous cell carcinoma was identified. Expression of nm23-H1 was evident in 9/25 (36%) CIN I, 13/28 (46%) CIN II, 22/28 (78.5%) CIN III and 17/25 (68%) infiltrating carcinoma biopsies. Statistically significant differences were observed between CIN II and CIN III (p=0.003), and CIN II and infiltrating carcinoma (p=0.002) groups. Expression of the nm23-H1 gene in premalignant and malignant cervical lesions indicates that this gene may play a substantial role in carcinogenesis and tumor progression.     

Significance of smoking and detection of serum antibodies to cytomegalovirus in cervical dysplasia

Summary. Cervical biopsy specimens from 422 women attending a colposcopy clinic showed various grades of dysplasia in 387 and no evidence of dysplasia in 35. Of the women with dysplasia (CIN I, II or III) 67% were smokers and 33% were non-smokers compared with 43% smokers and 57% non-smokers in those without evidence of dysplasia. Of the women with CIN I 56% were smokers and 44% were nonsmokers; 66% of those with CIN II were smokers and 34% were nonsmokers (P<0.02), and 71% of those with CIN III were smokers (P<0.01). There were no significant differences between the smokers and non-smokers in the proportion of women who had had either a miscarriage or an abortion, in the prevalence of condylomata acuminata, and the use of oral contraception or barrier methods. Neither were there any significant differences in numbers of patients seropositive for cytomegalovirus or in CMV antibody litres among the groups. The detection of koilocytic cells in cervical biopsies showed a significant difference between smoking and non-smoking groups which reflected a significant increase in koilocytosis in smokers with CIN III.     

Significance of smoking and detection of serum antibodies to cytomegalovirus in cervical dysplasia

Cervical biopsy specimens from 422 women attending a colposcopy clinic showed various grades of dysplasia in 387 and no evidence of dysplasia in 35. Of the women with dysplasia (CIN I, II or III) 67% were smokers and 33% were non-smokers compared with 43% smokers and 57% non-smokers in those without evidence of dysplasia. Of the women with CIN I 56% were smokers and 44% were non-smokers; 66% of those with CIN II were smokers and 34% were non-smokers (P less than 0.02), and 71% of those with CIN III were smokers (P less than 0.01). There were no significant differences between the smokers and non-smokers in the proportion of women who had had either a miscarriage or an abortion, in the prevalence of condylomata acuminata, and the use of oral contraception or barrier methods. Neither were there any significant differences in numbers of patients seropositive for cytomegalovirus or in CMV antibody titres among the groups. The detection of koilocytic cells in cervical biopsies showed a significant difference between smoking and non-smoking groups which reflected a significant increase in koilocytosis in smokers with CIN III.     

Is visual inspection with acetic acid better than cervical cytology to screen women ≥40?years of age for carcinoma cervix? A cross-sectional study on proportion of screen-positive women (by VIA and cervical cytology) having CIN II/III lesion on cervical biopsy: difference between two age groups and among screening methods

Objective

Proportion of CIN II/III lesion on cervical biopsy among screen-positive women of age group <40?years and ≥40?years undergoing screening for carcinoma cervix by Pap smear and visual inspection of cervix with acetic acid (VIA) was determined (both the tests were performed on same population). Difference in proportion of CIN II/III lesion among screen-positive women, between two age groups (for both methods) and between methods (for both age groups) was determined.

Result

In <40?years age group, proportion of screen-positive women with CIN II/III lesion was similar for both cytology or VIA (12.95 vs. 9.8%). For ≥40?year age group, compared to cytology, VIA detected higher proportions of CIN II or III lesion (4.1 vs. 13.3%). Proportion of screen-positive women having CIN II/III lesion was higher in <40?years compared to ≥40?year age group (12.95 vs. 4.1%) with cytology, while for VIA no difference was detected in between age groups (9.8 vs. 13.3%).

Conclusion

Cytological screening is less sensitive in women ≥40?years while VIA has a uniform sensitivity for both groups.     

Prevalence of human papillomavirus DNA in cervical tissue. Retrospective analysis of 855 cervical biopsies

The histopathologic features of 855 cervical biopsies were correlated with the presence of human papillomavirus DNA using in situ hybridization (ISH) with biotin labeled type specific probes for Human Papilloma Virus (HPV) types 6, 11, 16, 18, 31, 33 and 51. HPV-DNA was found in 18% (13/72) of cervical intraeptihelial neoplasia I (CIN I), 30% (35/115) of CIN II, 28% (57(206) of CIN III, in 84% (21/25) of flat condyloma and in 13% (15/112) of normal cervical tissue. HPV DNA was detectable in 11% (5/46) of cervical adenocarcinoma and in 21% (59/279) of squamous cell carcinoma (SCC) of the cervix. High risk HPV types were identified more often than low risk HPV types in CIN I, CIN II, CIN III and SCC. HPV type 16/18 predominates over HPV type 31/33/51 in CIN I, flat condyloma and in SCC. The prevalence of HPV was strongly associated with the grade of differentiation of SCC. It was identified in 59% (23/39) of well differentiated SCC, in 18% (25/142) of moderately differentiated and in 11% (11/98) of poorly differentiated SCC. Received: 29 March 1996 / Accepted: 15. August 1996     

Correlation of the histologic appearance of intraepithelial neoplasia of the cervix with human papillomavirus types. Emphasis on low grade lesions including so-called flat condyloma

Cervical condylomas and intraepithelial neoplasia (CIN) were correlated with human papillomavirus (HPV) types and analyzed for the presence of abnormal mitotic figures. Colposcopically directed cervical biopsies were divided in half and processed for routine microscopy and Southern blot hybridization. Of 83 specimens from 71 patients, 70 (84%) contained HPV-DNA sequences. The HPV distribution was as follows: HPV 16 in 6/25 flat condylomas (FC), 2/8 CIN I, 8/18 CIN II, 12/14 CIN III; HPV 18 in 1/25 FC; HPV 31 in 3/25 FC, 3/18 CIN II, and 1/14 CIN III; HPV 6/11 in 12/18 exophytic condylomas (EC), 5/25 FC, 2/8 CIN I, and 3/18 CIN II. Uncharacterized HPVs were identified in 4/18 EC, 5/25 FC, 2/8 CIN I, and 1/18 CIN II. A similar heterogeneous distribution of HPV types was found in flat condylomas and CIN I. A more homogeneous distribution was noted in the exophytic condylomas and high grade CIN lesions, with HPV 6/11 found in the former and predominantly HPV 16 in the latter. Abnormal mitotic figures were predominantly seen in the high grade CIN lesions. Based on our findings, we would recommend that the term flat condyloma be abandoned and that low grade flat lesions of the cervix be graded according to CIN criteria.     

Inflammatory atypia on cervical smears. A diagnostic dilemma for the gynecologist

In light of the current controversy on the significance, follow-up and management of women with cervical smears showing "inflammatory atypia" (IA), a study was conducted to correlate the initial cytologic diagnosis of IA with the follow-up findings in colposcopically directed cervical biopsies and smears. From March 1988 through June 1989, 70 women had two consecutive smears reported as IA; all underwent colposcopy and cervical biopsy. In 58 patients (83%) the biopsies and smears obtained during colposcopy were negative for condyloma and/or cervical intraepithelial neoplasia (CIN). Ten patients (14%) had condylomas, and two (3%) had condylomas with CIN (one CIN I and one II). The initial IA smears from those 12 patients were reviewed retrospectively: 2 showed condylomas (they had been undercalled), 5 were "suggestive of condyloma" (the atypical cells were too few or poorly preserved for a definitive diagnosis), and 5 showed IA. None showed cytologic evidence of CIN, most probably because of sampling error. Our results suggest that colposcopy is warranted after two consecutive diagnoses of IA on cervical smears, considering that 17% of the patients in our study showed underlying intraepithelial lesions of the cervix.     

Cervical papillomavirus infection and intraepithelial neoplasia: a study of male sexual partners

The male sexual partners of 34 women with cervical condyloma or cervical intraepithelial neoplasia (CIN) were examined for penile condylomata and/or urinary tract lesions. External lesions were detected in 18 (53%) of the male consorts of women with cervical lesions including 14 of 22 whose consorts had cervical condyloma or low grade CIN, one of six whose consorts had CIN 2, and three of six whose consorts had CIN 3. The majority of lesions were present either on the glands or the penile shaft, and one patient had a lesion in the urethral meatus. The urinary cytology specimens from the men with and without penile lesions contained nonspecific abnormalities consisting of squamous metaplasia with mild degrees of cytologic atypia. Koilocytotic atypia characteristic of condyloma was not found except in cases with documented distal urethral condylomata. Hence, at present the diagnosis of human papillomavirus infection in the man is best made by careful clinical examination. Whether or not papillomavirus resides deep in the urinary tract of these patients remains to be determined.     

Evaluation of adenoassociated virus 2 and human papilloma virus 16 and 18 infection in cervical cancer biopsies

OBJECTIVE: Protective roles of adenoassociated virus (AAV) 2 in cervical tumorigenesis are controversial. In an effort to clarify this issue, we tested prevalence of AAV 2 and human papillomavirus (HPV) infection in cervical lesions and adjacent normal tissues. METHODS: Tissues of cervical intraepithelial neoplasm (CIN) I (20 patients), CIN II (24 patients), CIN III (25 patients), and invasive cancer (23 patients) were investigated by microdissection and PCR using HPV-16-, HVP-18-, and AAV-2-specific primers. RESULTS: AAV 2 was detected in 11 out of 20 CIN I (55%), 21 out of 24 CIN II (84.5%), 13 out of 25 CIN III (52%), and 12 out of 23 invasive cancer cases (52.2%). However, HPV 16 was detected in none out of 20 CIN I, 2 out of 24 CIN II (8.3%), 6 out of 25 CIN III (24%), and 6 out of 23 invasive cancer cases (26.1%). HPV 18 was detected in 1 case in CIN II (4.2%) and 2 cases in CIN III (8%). In 92 perilesional normal tissues, AAV 2 was detected in 53 cases (57.6%), displaying 25% of CIN I, 83.3% of CIN II, 52% of CIN III, and 65.2% of invasive cancer. CONCLUSION:The differences in AAV 2 prevalence are not significant between CIN and normal tissues. However, differences in HPV 16 are significant in CIN III and invasive cancer, as compared to CIN I, CIN II, and normal, suggesting no significant correlation between AAV 2 and cervical cancer. Thus, these results support the notion that AAV 2 is not associated with cervical tumorigenesis.