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Biomedical subjects

D J McCance

Publications and source records attributed to D J McCance.

At least 55 records · Page 3Linked to original sources
PubMed1989

Screening for cervical carcinoma.

At present, cytological examination of cervical smears is the method used to screen the female population for cervical abnormalities. This employs the Papanicolaou staining technique and cell morphology to detect abnormal cells from the susceptible transformation zone of the cervix. However, with the recent discovery of a possible link between human papillomavirus (HPV) infection and cervical cancer, a test to determine the presence of HPV infection may be appropriate. Tests are still at a developmental stage and at present used only for research purposes. Various DNA-DNA or DNA-RNA hybridisation techniques are employed in experimental screening studies, and these involve probing cells or DNA extracted from cells for HPV DNA using radio-labelled probes.

Cervix Uteri↗
PubMed1988

DNA sequence of the HPV-16 E5 ORF and the structural conservation of its encoded protein.

Infection of cervical epithelium by human papillomavirus type 16 (HPV-16) appears to be closely associated with the development of cervical dysplasia and carcinoma. By inference from genetic and biochemical studies of the bovine papillomavirus, the E5 ORF of the human papillomaviruses is anticipated to encode a "transforming" protein. In an effort to compare the E5 ORF of HPV-16 with other human papillomaviruses and bovine papillomavirus, we sequenced this region from a new isolate of HPV-16 which was derived from extrachromosomal viral DNA within a premalignant cervical lesion (cervical intraepithelial neoplasia, grade III, or CIN III). In addition, we also sequenced the original isolate of HPV-16 (derived from integrated viral DNA by Durst et al. [Proc. Natl. Acad. Sci. USA 80, 3812-3815 (1983)] and sequenced by Seedorf et al. [Virology 145, 181-185 (1985)]. Both HPV-16 isolates contained an additional nucleotide (T) at bp 3906. This nucleotide addition caused a frameshift in the E5 ORF such that it now contains an initiation codon at bp 3849; the frameshift also alters the predicted E5 NH2 terminus but retains the original COOH half of the protein. E5 proteins encoded by several HPVs which infect the genital region (e.g., types 6, 11, 16, 18, 33) exhibit a conserved trimodal hydrophobic structure, but not a conserved amino acid sequence.

Amino Acid Sequence↗
PubMed1988

Human papillomavirus type 16 alters human epithelial cell differentiation in vitro.

Human papillomavirus (HPV) types 16, 18, 31, and 33 have been implicated as etiologic agents of cervical and penile cancer. Using a cell culture system for keratinocytes which allows stratification and production of differentiation-specific keratins, we have examined the effects of one of these viruses, HPV-16, on the differentiation capabilities of human epithelial cells. A plasmid containing the HPV-16 genome and a neomycin-selectable marker was transfected into primary human epidermal cells and SCC-13 cells, an immortalized squamous cell carcinoma cell line. Cloned neomycin-resistant cell lines were isolated and examined by cell culture on raised collagen rafts. Cell lines containing HPV-16 DNA retained the ability to stratify and express differentiation-specific keratins in the raft system but otherwise failed to differentiate normally. The histological abnormalities induced by HPV-16 closely resembled those seen in genital intraepithelial neoplasia in vivo. Hence, our results support the role of HPV-16 as an etiologic agent in the development of genital neoplasias and suggest a specific system for the study of HPV-16-induced epithelial cancers.

Blotting, Southern↗
PubMed1988

Psychosexual trauma of an abnormal cervical smear.

The psychosexual sequelae of diagnosis and treatment of pre-invasive cervical atypia were assessed in three groups of women. The first group included 30 women referred to a colposcopy clinic with an abnormal cervical smear indicating cervical intraepithelial neoplasia (CIN), the second comprised 50 women who were traced as sexual partners of men with penile human papillomavirus (HPV) infection; 26 of them had histologically proven cervical atypia and 24 had no such evidence. The third group included 25 women traced as partners of men with non-specific urethritis and who did not have cervical disease. Before and after questionnaires assessed six aspects of sexual behaviour and responses before diagnosis and 6 months after treatment in women with cervical atypia. These were compared with answers given by women investigated and treated, if necessary, as partners of men with sexually transmitted disease (control group). There were statistically significant adverse psychosexual sequelae associated with diagnosis and treatment of pre-invasive cervical epithelial disease.

Adult↗
PubMed1988

Detection of human papillomavirus DNA sequences by in situ DNA-DNA hybridisation in cervical intraepithelial neoplasia and invasive carcinoma: a retrospective study.

Human papillomavirus (HPV) infection of cervical intraepithelial neoplasia (CIN) and invasive cervical carcinoma was investigated using in situ DNA-DNA hybridisation on histological sections of formalin fixed, paraffin embedded tissue to assess the technique's sensitivity and to assess retrospectively the association between HPV16 and invasive cervical carcinoma. HPV DNA was detected in 16 of 33 biopsy specimens of CIN. Cells containing viral DNA were more numerous than those positive for viral structural proteins. HPV DNA was also present in less differentiated cells deeper in the epithelium. The detection rate in CIN was lower than that reported for other hybridisation techniques such as Southern blotting. In a retrospective study of biopsy specimens of invasive squamous carcinoma of the cervix HPV16 DNA, the virus most commonly associated with cervical malignant disease, was found in 20 of 25 cases, including those dating from as far back as 1932. The level of sensitivity was similar to that reported for other hybridisation techniques. DNA positive cells were focally distributed in the invasive tumours, and most tumour cells were negative for viral DNA, a result consistent with the low copy number found in malignant cells. It is concluded that HPV16 is not a new virus but that its prevalence is a result of changes in sexual behaviour and that in situ hybridisation is useful in the localisation of HPV DNA replication in CIN and invasive carcinoma.

DNA, Viral↗
PubMed1988

Subclinical penile human papillomavirus infection and dysplasia in consorts of women with cervical neoplasia.

Fifty men whose sexual partners were 50 women with histologically proved cervical intraepithelial neoplasia (CIN) grade III (severe dysplasia or carcinoma in situ) were studied. A further 25 men whose current regular sexual partners were 25 women with chlamydial cervicitis were recruited as controls. If either of the partners in either group had genital condylomata acuminata or a known history of similar lesions, the couple was excluded from the study. Abnormal penile epithelium, which was detected by colposcopy after application of 5% acetic acid to the penile skin, was reported in 25 men in the study group compared with three in the control group. Histologically proved subclinical penile infection with human papillomavirus (HPV) was present in 23 men in the study group compared with three in the control group (p less than 0.01). Of the 50 men in the study group, four had histologically proved severe penile dysplasia or carcinoma in situ with evidence of HPV infection, the disease being subclinical in each case and diagnosed on histology of a specimen obtained by colposcopically directed biopsy. HPV DNA was detected on filter hybridisation of penile scrapes from 15 of the 23 men in the study group with histologically proved penile HPV infection, HPV16 DNA being detected in 10 of them. HPV DNA was detected on DNA-DNA hybridisation of biopsy material in seven of 18 men with histologically proved penile HPV infection. Five of these biopsy specimens were positive for HPV16 DNA. Only one man in the control group had HPV DNA detected in a penile scrape. This patient had histologically proved subclinical penile HPV infection. Such lesions may represent an important male reservoir of HPV types implicated in genital squamous carcinogenesis in both sexes.

Adult↗
PubMed1988

Risk factors in the development of cervical intraepithelial neoplasia in women with vulval warts.

Of 59 women referred with vulval warts whose cervices were assessed colposcopically for the presence of cervical intraepithelial neoplasia (CIN) before local treatment of the wart lesions, 17 had histologically proved CIN, 12 had histologically proved cervical wart virus infection, and 30 had abnormality on colposcopy or cytology. Seven of the 17 with CIN had no abnormality on cervical cytology. No differences in sexual behaviour, smoking habit, or oral contraceptive use were seen between women with CIN and those with no cervical abnormality. Viral DNA typing of the vulval lesions was carried out, but there were no differences in the distribution of viral types between the three different histological groups. Of the 30 women with no abnormality at the initial visit, 23 were followed up colposcopically and cytologically for one to two years. Three of them developed CIN after adequate treatment of the vulval lesions despite the absence of cervical abnormalities on colposcopy at the time of treatment. Studying the known factors linked with CIN failed to show why some women with vulval warts develop CIN, even after treatment of the warts, and others do not. The large number of false negative results on cervical cytology in our patients suggests that women presenting with vulval warts should be screened colposcopically in the first instance. Close follow up of women whose warts are treated and who are thought to have no cervical abnormality at that assessment is essential.

Adult↗
PubMed1988

Human papillomavirus (HPV) infections in the aetiology of cervical cancer.

There is an association between human papillomavirus (HPV), in particular types 16 and 18, and premalignant and malignant disease of the cervix. At present it is not possible to say that this is a causal association but in vitro transformation studies indicate that these viruses can transform primary mammalian cells in cooperation with Ha-ras. This may mean that these viruses have at least a c-myc like activity which is consistent with their ability on their own to immortalize primary keratinocytes. The fact that HPV6 can also transform mammalian cells, at a low frequency, in cooperation with Ha-ras indicates the need to use appropriate cells and systems that will elucidate differences in virus-cell interactions between benign HPV types 6 and 11 and the viruses associated with severe disease 16 and 18.

Cell Transformation, Viral↗
PubMed1986

Progressive potential of mild cervical atypia: prospective cytological, colposcopic, and virological study.

A prospective study of 100 women with cytological and colposcopic evidence of mild cervical atypia consistent with cervical intraepithelial neoplasia (CIN) grade I was started in October, 1983. 26% of early preinvasive cervical lesions progressed to histologically proven CIN III. Spontaneous regression of mild cervical atypia occurred in only 11 cases, and in 4 of these CIN recurred. The overall prevalence of human papillomavirus type 16 (HPV 16) in the study group, detected by filter DNA-DNA hybridisation of a cervical cytological specimen, was 39%. However, 22 of the 26 (85%) cases of progressive disease were positive for HPV 16. Detection of HPV 16 may be a non-invasive way of identifying women at high risk of rapid progression of mild cervical atypia to CIN III.

Adult↗
PubMed1986

Human papillomavirus types 16 and 18 in carcinomas of the penis from Brazil.

Human papillomavirus (HPV) type-16 DNA sequences were found in 26/53 (49%) and HPV type-18 in 5/53 (9%) of penile cancers. In only one specimen was HPV18 found on its own. HPV16 sequences were integrated into the host cell chromosomes although some monomeric and oligomeric free forms of DNA were detected in a few tissues. HPV18 was, as far as detectable, free and unintegrated in all tissues tested. HPV16 DNA was also detected in 40% of cases of carcinoma of the cervix in 19 women from the same social groups as the males. The viral DNA in the female cases was a mixture of integrated and free forms. The DNA binding protein (ICSP 11/12) of herpes simplex type 2 (HSV2) was not detected in 10 penile cancers tested with a monoclonal antibody.

Antigens, Viral↗
PubMed1986

Histological and immunocytochemical study of cervical intraepithelial neoplasia (CIN) with associated HPV 6 and HPV 16 infections.

Histological and immunocytochemical features of cervical intraepithelial neoplasia (CIN) associated with HPV 6 and HPV 16, either singly or in combination, were studied in 48 cases. Features of HPV infection (koilocytosis, binucleation, multinucleation, giant irregular nuclei and individual cell dyskeratosis) were present in high prevalence in both HPV 6 and HPV 16 associated CIN. Abnormal mitoses seemed to be a good indicator of CIN and were present in about 50% of cases of CIN associated with either HPV 6 or HPV 16 infection. This finding provides no support for the view held by some investigators that associated HPV 16 infection can be predicted by the presence of abnormal mitoses. Expression of HPV antigen was shown in about 40% of cases with a slight, but not significantly, higher prevalence in cases of combined HPV 6 and HPV 16 infection. Conventional histology and immunocytochemistry could not distinguish CIN associated with HPV 6 from CIN associated with HPV 16 infection.

Antigens, Viral↗
PubMed1985

Increased risk of cervical neoplasia in consorts of men with penile condylomata acuminata.

19 (76%) of 25 women who had been the sole sexual consorts, for at least 1 year, of men with pre-existing penile condylomata acuminata had similar lesions of the lower genital tract. 9 (36%) of the women had an abnormal cervix as judged by cytology, colposcopy, and histology, and 7 (77%) of these 9 had associated human papillomavirus (HPV) infection detected by DNA/DNA hybridisation. None of 20 women in an age-matched control group had cytological or colposcopic evidence of cervical epithelial atypia. It is suggested that penile HPV infection in a male partner places a woman at risk of cervical neoplasia.

Adult↗