Human papillomavirus types 16 and 18 in adenocarcinoma of the uterine cervix

Fifty cervical adenocarcinomas and 50 squamous cell carcinomas from age-matched patients were examined for human papillomavirus (HPV) types 16 and 18. The polymerase chain reaction was used to examine formalin-fixed, paraffin-embedded carcinoma tissues for 120 and 113 bp sequences, respectively, of the highly conserved E6/E7 regions of the viral genomes. HPV type 16 was detected more often in squamous cell carcinomas than in adenocarcinomas (60% vs 18%, P less than 0.001). Conversely, HPV type 18 was detected significantly more often in adenocarcinoma tissues (52% vs 12% in squamous cell carcinomas, P less than 0.001). These differences may reflect the fact that different virus receptors exist in cervical cells with different morphologic potential, or they may indicate that the specific HPV infection actually plays a role in directing carcinogenesis.     

Human papillomavirus deoxyribonucleic acid in adenocarcinoma and adenosquamous carcinoma of the uterine cervix

This report describes the detection of human papillomavirus type 16 or 18 deoxyribonucleic acid (DNA) in nine of 15 invasive tumors of the cervix, including three squamous carcinomas, four adenosquamous carcinomas, one glassy cell carcinoma, and one adenocarcinoma. The viral DNA was identified by Southern blotting and DNA hybridization. Human papillomaviruses may play an etiologic role in the development of at least some adenocarcinomas and adenosquamous carcinomas as well as most squamous tumors of the cervix.     

Human papillomavirus messenger RNA expression in adenocarcinoma in situ of the uterine cervix

Over recent years, the association between human papillomavirus (HPV) and squamous cell carcinoma of the cervix and its precursors has been well established, largely as a result of advances in the techniques of molecular biology. A similar association between HPV and invasive adenocarcinoma of the cervix has also been recently demonstrated; however, little work has been published on the relationship between the precursor lesion, adenocarcinoma in situ (ACIS), and HPV. We have therefore undertaken an in situ hybridization study of 22 cases of known cervical ACIS using probes for HPV messenger RNA expression. Seventeen of these had residual ACIS in the blocks studied, 15 of which (88.6%) expressed HPV messenger RNA. Five cases were positive for HPV 16 and 10 cases for HPV 18. Early invasive adenocarcinoma was present with ACIS in three cases and one case had early invasion plus cervical intraepithelial neoplasia (CIN III). These invasive lesions showed a similar type and degree of HPV expression as the in situ component. One section had only residual CIN III, which was positive for HPV type 18. Four cases had only minor glandular atypias (less than ACIS) in the studied sections, and all four of these were negative for HPV expression. None of the normal endocervical epithelia in any of the sections were positive by this technique. In summary, the finding of HPV messenger RNA expression in nearly 90% of cervical ACIS supports a possible role for these viruses in the pathogenesis of glandular neoplasms of the uterine cervix.     

生殖道人乳头状瘤病毒感染后子宫颈局部免疫反应的变化

生殖道人乳头状瘤病毒(humanpapillomavirus,HPV)的感染是全世界流行的疾病,至少5 0 %的性活跃妇女有生殖道HPV的感染。生殖道HPV感染需要增殖的细胞为宿主,宫颈的HPV特异性地感染鳞柱交界处基底和旁基底细胞,HPV感染是宫颈恶性肿瘤的主要流行病学危险因素,宫颈局部HPV持续感染与宫颈上皮内瘤变(CIN)及宫颈癌关系密切[1] 。但大多数HPV感染是一过性的,其症状不明显,与局部的自然免疫有关。本文就宫颈HPV感染的局部免疫及其变化作一综述。一、HPV种类、结构及致病机制HPV于194 9年由Strauss在电镜下发现,是一种环状双链结构的D…     

Human papillomavirus genotype as a prognostic indicator in carcinoma of the uterine cervix

The clinical implications of specific human papillomavirus (HPV) types in invasive cervical carcinomas are only beginning to be appreciated. In this series of 100 women with cervical cancers analyzed for the presence of HPVs 6, 11, 16, 18, and 31 by Southern blot hybridization, a more aggressive clinical behavior was demonstrated for tumors containing HPV 18 than for those with HPV 16 or those in which no HPV was identified. Among 69 stage Ib tumors, no significant differences were found in the size of tumor, presence of parametrial involvement, or lymph node metastasis among patients whose tumor contained HPV 16, HPV 18, or no HPV DNA; however, 45% of the women with HPV 18-containing tumors (five of 11) had recurrence, as compared with only 16% of those with HPV 16 (five of 31) during the 20-month mean follow-up period. This tendency for HPV 18-containing tumors to recur was seen with all histologic subtypes of cervical cancers and with all grades of tumor. In addition, patients with HPV 18-containing tumors were more likely to give a history of recent normal Papanicolaou smears than were those whose tumors contained HPV 16. Forty-four percent of women with HPV 18 in their tumors had a history of three class I Papanicolaou smears in the 3 years before the diagnosis of cancer, whereas a similar history was elicited in only 16% of those with HPV 16 in their tumors, suggesting that HPV 18-containing tumors might progress to invasion without a prolonged preinvasive period.     

Human papillomavirus genotype as a prognostic factor in carcinoma of the uterine cervix

The clinical implications of specific human papillomavirus (HPV) types in invasive cervical carcinomas are only now beginning to be appreciated. The objective of this study was to determine the clinical implications and prognostic value of the HPV genotype in cervical carcinomas. In this study, we employed an HPV DNA chip to detect the type-specific sequence of HPV from cervical swabs taken from women with biopsy-proven neoplastic lesions of the cervix. We divided the patients into four groups: HPV-negative, HPV-16-related, HPV-18-related, and intermediate risk type-related. Associations with clinicopathologic data (stage, histologic type, lymph node status, parametrial invasion, lymphvascular space invasion, tumor size, vaginal involvement) and overall survival were assessed. HPV DNA was detected in 81.4% of the patients, and 19.0% harbored multiple HPV variants. HPV-16-related was the predominant type and was detected in 47.4% (46/97) of the patients. The HPV-16-related types were detected more frequently in patients with squamous cell carcinomas, whereas the HPV-18-related types were more prevalent in cases of adenocarcinomas and adenosquamous carcinomas (P < 0.05). Otherwise, no significant correlations were detected between the HPV genotype and any other clinicopathologic parameters. After a median follow-up of 30 months, the 5-year survival rate was lower in the HPV-18-related patients, but this difference was not found to be statistically significant, according to the results of the log-rank test. We conclude that neither the presence nor type of HPV DNA bears any prognostic significance in cases of cervical carcinoma.     

Human papillomavirus type 18 DNA sequences in adenocarcinoma and adenosquamous carcinoma of the uterine cervix

Human papillomavirus (HPV) DNA sequences were detected by Southern blot hybridization and polymerase chain reaction (PCR) in 10 out of 19 patients (52.7%) with adenocarcinoma [15] and adenosquamous [4] carcinoma of the uterine cervix. HPV 18 DNA was detected in 8 of these 19 patients (42.1%), HPV 16 DNA in 1 patient (5.3%) and HPV type X (unknown) in another (5.3%). Of the 10 HPV positive samples HPV 18 was found in 6 out of 6 pure adenocarcinomas (100%), and in 2 of 4 (50%) adenosquamous carcinomas. HPV 16 and HPV X were each detected in 1 out of 4 (25%) adenosquamous carcinomas. The physical state of the viral DNA was investigated in 5 of the 10 HPV-positive cases. All the specimens from these 5 cases showed HPV to be integrated into the host genome, except for one adenosquamous specimen, which showed both episomal and integrated forms of HPV 16. Six of 8 HPV 18 DNA positive specimens were from cases of pure adenocarcinoma and it was found by PCR that five of these 6 specimens retained fragments of E6/E7, LCR/E7 and early sequence of E1 fragment (sequence: 1188–1373) but deleted most part of E1.     

Human papillomavirus and its prognostic significance in invasive carcinoma of the cervix in young patients.

Of 1,200 Chinese patients treated for carcinoma of the cervix between 1975 and 1984, those aged 40 years (n = 70) or less had a poorer prognosis. Of the latter group, 71% had disease classified as less than International Federation of Gynecology and Obstetrics (FIGO) stage Ib, and in 91% the disease was less than stage IIa; however, the 5-year survival of the 45 patients with verified invasive carcinoma was 75% compared with 82% for the overall group. The polymerase chain reaction (PCR) was used to test for the presence of human papilloma virus (HPV) types 16 and 18 within paraffin-embedded tissue from the primary tumors. HPV-16 DNA sequences were detected in 69% of the cases, HPV-18 DNA sequences in 44%, and in 31% both HPV-16 and -18 DNA could be identified. Of the cases of invasive carcinoma, 82% (37 of 45) contained DNA of HPV types 16 and/or 18. The effects of the presence or absence of HPV DNA on known prognostic factors was investigated. Although the influence of traditional factors, especially lymph node involvement, was confirmed, careful statistical analysis could not demonstrate a prognostic influence for HPV-16/18.     

Human papillomavirus DNA in triple neoplasms of the cervix, perianus and ureter in one woman

BACKGROUND: Multiple malignancies of the urogenital tract have been reported. We investigated the etiological role of human papillomavirus (HPV) in the pathogenesis of urogenital cancers. CASE: We present a case of cervical squamous carcinoma in a 64-year-old woman who subsequently developed Bowen's disease in the perianal skin and transitional cell carcinoma of the ureter. HPV DNA was detected in these tumor specimens using polymerase chain reaction. CONCLUSION: The results strongly suggest that HPV may play a major role in the carcinogenesis of urogenital and perianal tumors.     

Human papillomavirus testing in the clinical laboratory. Part I: squamous lesions of the cervix

The aim of this study was twofold: (1) to evaluate the contribution of viral (HPV) testing for improving the sensitivity of cervical cytology and (2) to correlate HPV types with the histology of the detected cervical cancer precursors, particularly the low-grade, CIN I variant. We used the dot blot hybridization technique (ViraPap) and polymerase chain reaction (PCR) in 63 women referred to our colposcopy clinic for evaluation of an abnormal Pap test. Histopathologic samples obtained by multiple colposcope-directed punch biopsies were used for a diagnostic gold standard. Among the 53 women with histologically proven CIN, precolposcopy cytology was positive in 38 (72%) compared to 53% and 60% HPV positivity by ViraPap and PCR, respectively (p less than 0.01). When the yields of ViraPap/PCR and cytology were combined, however, the detection rate of CIN was 91%, a significant improvement over cytology alone (p less than 0.02). HPV DNA was found either by ViraPap or PCR in 45 of 63 (71%) biopsy specimens, and 37 of 38 (97%) HPV-positive CIN, including the low-grade CIN I variant, contained oncogenic HPV types. HPV type 16 was present in 22 of 38 (58%) CIN lesions and mixed with HPV 6/11, 18, or the 30s group in 6 of 38 (16%) of the cases. HPV 6/11 alone was found only in 1 case of CIN I (2.7%). HPV testing by molecular technology increases the sensitivity of cytology.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human papillomavirus associated with adenocarcinoma and adenosquamous carcinoma of the cervix: analysis by in situ hybridization

The incidence of adenocarcinoma of the cervix appears to be increasing. Recent reports have demonstrated an association between adenocarcinoma of the cervix and human papillomavirus (HPV) by Southern blot hybridizations. In situ deoxyribonucleic acid (DNA) hybridization was performed on paraffin-embedded specimens to localize the source of HPV DNA. In pure adenocarcinoma five of six specimens were positive for HPV DNA. Four specimens contained HPV type 18 and one HPV type 16. Only one of three adenosquamous lesions was positive and it contained both HPV types 16 and 31. These findings suggest an association between HPV and adenocarcinoma of the cervix.     

Human papillomavirus DNA in glandular dysplasia and microglandular hyperplasia: presumed precursors of adenocarcinoma of the uterine cervix

Presumed precursors of adenocarcinoma of the uterine cervix were investigated with specific techniques to identify human papillomavirus (HPV) DNA. The presence of HPV DNA in 36 lesions of glandular dysplasia and 16 lesions of microglandular hyperplasia of the uterine cervix was studied by in situ hybridization using 3H-labeled HPV 16 and HPV 18 DNA probes. Only two of 36 lesions (6%) of glandular dysplasia contained HPV 18 DNA, although 64% of coexisting adenocarcinoma in situ, microinvasive adenocarcinoma, and cervical squamous intraepithelial neoplasia III lesions contained HPV 18 and/or HPV 16 DNA. Two lesions of HPV 18 DNA-positive glandular dysplasia coexisted with adenocarcinoma in situ that contained the same type of HPV DNA. None of the microglandular hyperplasia lesions contained HPV 16 DNA or HPV 18 DNA. These results suggest that, if HPV infection is an initial step toward carcinogenesis, it is unlikely that glandular dysplasia and microglandular hyperplasia are precursor lesions of adenocarcinoma of the uterine cervix. A large proportion of glandular dysplasia may represent reactive lesions of endocervical columnar epithelium. Two lesions of HPV 18 DNA-positive glandular dysplasia may represent well-differentiated components of adenocarcinoma in situ of the uterine cervix.     

Circular suture of the cervix in placenta praevia]

In the accidents of placenta praevia a modified cervixcerclage was used to 25 women during gestation period of 20 to 35 weeks. The circulare suture goes under the bundles of uterine oessels. This inables to escape the lesions of oessels and dystrophy of the cervix uteri. The circulare suture helps to reduce a number of premature labours. The labours were delayed for 23 days and fetal mortality reduced to 10,53%. Cervixcerclage is indicated. Fetal mortality to prevent fetal mortality and to prolonge the pregnancy.     

Human papillomavirus

Human papillomaviruses are ancient small DNA viruses and represent the most common sexually transmitted infection in the world. In the majority, HPV infection is cleared by an incompletely understood immune response. HPV is a necessary but not sufficient cause of cervical cancer, and responsible for a proportion of other anogenital cancers including vulval, vaginal, anal and oropharyngeal. Oncogenesis is likely mediated through viral proteins which hijack host-cell machinery in epithelial keratinocytes and disrupt host tumour-suppressor proteins. Much work has been undertaken to further characterise the natural history of HPV infection and cervical disease. Such efforts have been translated to important public health interventions like the introduction of HPV tests in cervical screening. HPV vaccination programmes are expected to further reduce the incidence of high-risk HPV infections and resultantly HPV-related disease.     

Human papillomavirus infection of the cervix: relative risk associations of 15 common anogenital types.

During the years 1982-1989, 2627 women were recruited into eight studies analyzing the relationship between human papillomavirus (HPV) infection and cervical neoplasia. Subsequently, each individual was assigned as either a case or control, and each cervical sample was rescreened for HPV DNA by low-stringency Southern blot hybridization. Positive samples were retested at high stringency with specific probes for HPVs 6/11, 16, 18, 31, 33, 35, 42, 43, 44, 45, 51, 52, 56, and (in most instances) 58. Most cases (153 cancers, 261 high-grade and 377 low-grade squamous intraepithelial lesions) had target or cone biopsies; all 270 borderline atypia subjects and more than 85% of the 1566 normal controls had cytology plus colposcopy/cytology. Scientists performing HPV testing were masked to the clinical diagnoses. Human papillomavirus DNA was detected in 79.3% of specimens from women with definite cervical disease (627 of 791), in 23.7% of borderline atypia subjects (64 of 270), and in 6.4% of normal subjects (101 of 1566). Graphic analysis of odds ratios at each point in the diagnostic spectrum defined four categories: 1) "low risk" (HPVs 6/11, 42, 43, and 44), present in 20.2% (76 of 377) of low-grade lesions but absent in all 153 cancers; 2) "intermediate risk" (HPVs 31, 33, 35, 51, 52, and 58), detected in 23.8% (62 of 261) of high-grade squamous intraepithelial lesions but only 10.5% (16 of 153) of cancers; 3) "high risk/HPV 16," associated with 47.1% of both high-grade intraepithelial lesions (123 of 261) and cancers (72 of 153); and 4) "high risk/HPV 18" (HPVs 18, 45, and 56), found in 26.8% (41 of 153) of invasive carcinomas but only 6.5% (17 of 261) of high-grade intraepithelial lesions. The presence of an oncogenic HPV type conferred relative risks ranging at 65.1-235.7 for the occurrence of a high-grade lesion and 31.1-296.1 for an invasive cancer.     

Localized distribution of human papillomavirus genotypes in the uterine cervix

INTRODUCTION: The localization and distribution of single or multiple HPV genotypes in the uterine cervix has not been studied thus far. The present study was undertaken to determine whether single or multiple HPV genotypes detected in cervical smears originate from a single (dysplastic) area, or from different areas (dysplastic or normal) of the uterine cervix. METHODS: Of eight patients with moderate or severe dysplasia, 31 colposcopically guided biopsies of different dysplastic lesions of the uterine cervix, as well as of normal epithelium were investigated. A highly sensitive, broad spectrum, short fragment polymerase chain reaction (SPF-10 PCR) HPV detection method in combination with a line probe assay (LiPA) for simultaneous genotyping was used. RESULTS: In the uterine cervix of four of the eight patients, multiple HPV genotypes were detected. These multiple HPV genotypes were detected in different biopsies as well as within a single biopsy. In three patients, all with carcinoma in situ or microinvasive carcinoma, only a single HPV genotype, HPV 16, was found all over the cervix including in the normal epithelium. CONCLUSION: Different HPV genotypes can be detected in different dysplastic lesions as well as within single lesions, especially in patients with severe dysplasia. The severity of the lesion may possibly have a relation with the distribution of the HPV genotypes. The low number of patients and biopsies does not allow definite conclusions. However, the impact of these findings on the outcome of screening and vaccination programs remains to be elucidated.     

Colposcopy in women with papillomavirus lesions of the uterine cervix

Colposcopic examinations for human papillomavirus lesions were performed in 271 women, some of whom had developed concomitant cervical intraepithelial neoplasia since 1981. The colposcopic appearance was classified into one of the following categories: normal, punctate, mosaic, warty, leukoplakial, or combination, and was related to findings in Papanicolaou smears and punch biopsy specimens. There was a good correlation between the colposcopic appearance and the findings in the Papanicolaou smears and punch biopsy specimens, facilitating the diagnosis of the lesions. The accuracy of colposcopy in disclosing the atypias varied according to the growth pattern of the papillomavirus lesions, with the most accurate (100%) in cases of papillomatous condylomas, and the least accurate (50%) in the inverted lesions. White epithelium and combination patterns were most frequently associated with the papillomavirus lesions and cervical intraepithelial neoplasia, as evidenced by both cytology and biopsy. During the follow-up, normal colposcopic appearance increased from 32 to 50%, reflecting the established spontaneous regression of a certain percentage of the cervical lesions, or their regression as a result of biopsy. The results are discussed in terms of the mutually complementary roles of colposcopy, cytology, and biopsy, and in view of the clinical behavior of cervical papillomavirus lesions. Colposcopy is mandatory for adequate prospective follow-up of these patients but should not replace cytology and punch biopsy.     

Colposcopy in the diagnosis of papillomavirus infection of the uterine cervix

Morphological criteria are described for the diagnosis of papillomavirus lesions at colposcopy. Using these criteria, evidence of cervical papillomavirus infection was found in 58 (29.0%) of 200 women referred for colposcopy because of an abnormal cytology report. Directed biopsies were obtained from 152 of these patients and histological changes suggestive of papillomavirus infection were found in 47 (30.9%); additional biopsy material from 139 was studied using an immunohistochemical technique and human papillomavirus antigen was demonstrated in 28 (20.1%). Comparison between the colposcopic results and those obtained by histology suggests that whereas it is not possible to make a distinction at colposcopy between lesions due to papillomavirus and those of cervical intraepithelial neoplasia, it is possible to identify those epithelial abnormalities that are most likely to be associated with a papillomavirus infection.     

Colposcopy in the diagnosis of papillomavirus infection of the uterine cervix

Summary. Morphological criteria are described for the diagnosis of papillomavirus lesions at colposcopy. Using these criteria, evidence of cervical papillomavirus infection was found in 58 (29.0%) of 200 women referred for colposcopy because of an abnormal cytology report. Directed biopsies were obtained from 152 of these patients and histological changes suggestive of papillomavirus infection were found in 47 (30.9%); additional biopsy material from 139 was studied using an immunohisto-chemical technique and human papillomavirus antigen was demonstrated in 28 (20.1%). Comparison between the colposcopic results and those obtained by histology suggests that whereas it is not possible to make a distinction at colposcopy between lesions due to papillomavirus and those of cervical intraepithelial neoplasia, it is possible to identify those epithelial abnormalties that are most likely to be associated with a papillomavirus infection.