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Title: Age related changes in the human cervix uteri with reference to the development of neoplasia
Author: Roberts, Anthony Deans Guthrie
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1987
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This thesis,has attempted to indicate, that the cervix after the menopause,is a considerably different organ from that of the younger woman. A paradox now exists with carcinoma of the cervix, namely high incidences of pre-invasive disease in the younger woman, and low incidence of carcinoma, which contrasts with the situation in the older patient, who has high incidence of invasive disease, and low incidences of pre-invasive disease. This has led to the suspicion of two different aetiologies. The older patient may not progress through a detectable pre-invasive phase, as low rates of carcinoma in situ in the older woman would suggest (209). Thus, age itself, may be a co-variable in the genesis of disease (92,93). This questions whether the agents that are putative causes for cervical cancer, in the younger woman, are also aetiological factors in the older woman. The work in chapter two, defined the colposcopic appearances of fifty peri- and postmenopausal women,who had symptoms of the climacteric, and were to be prescribed hormone replacement therapy (HRT). Colposcopic and cytologic variables were compared and related to serum analyses of oestradiol. A scoring system was devised, to enable the effect of HRT to be quantitated. HRT improved the colposcopic appearance of the cervix, and enabled the SCO to be seen, when previously it was not visible. Other work,carried out on the same patients, indicated that twelve of the fifty patients (24%),had a colposcopic abnormality or atypical transformation zone. Of greater alarm, was that four of these eleven patients,had histologically proven CIN, without any cytological abnormality, despite repeated smearing. Doubt has been cast on the ability of these CIN lesions, in the postmenopausal patient ,to exfoliate abnormal cells, at least in the early grades of CIN found in this study. This has not been encouraging to the concept that cytology may be discontinued at the age of 60 years, if it has been negative up to that age (21). The second section of the work of this thesis, considered the factors that have been proposed as causal to carcinoma of the cervix. A population of women with carcinoma of the cervix, were matched with a population of women of like age, parity, and socio-economic group, who had no previous evidence of cervical neoplasia. Three putative agents, which lend evidence of past infection were studied. No conclusive evidence could be found, to implicate any agent or combinations of agents. A trend, however, appeared with C. trachomatis and tumour differentiation, and it is possible that this agent, or combinations involving this agent, are implicated in more aggressive tumours. Data on socio-economic grouping,proved crucial to the study. Seropositivity appears intimately related to S.E. group, and indicates the severe limitations of studies which do not have this information. Perhaps the greatest value of this work, lies in the illustration of seropositivity with age. The patient under the age of thirtyfive years, with carcinoma of the cervix, had much higher rates of seropositivity to all three agents, but especially to C. trachomatis and CMV, than the control patient. The older patient who had had carcinoma of the cervix, had almost identical seropositivity rates to the control patients. This is further evidence that carcinoma in the older patient, may be of different origins to the carcinoma in the younger patient. One problem with these data, is the dominance of carcinoma among the older woman, thus burying any significant differences evident only in the younger woman, who have developed carcinoma. The next section of the work, was to identify agents associated with CIN, and to compare these to a population of normal women, and healthy postmenopausal women. HPV was confirmed as an agent commonly associated with CIN, but no other agent was more commonly associated, than in the control group. The identification of a group with abnormal cytology and negative colposcopy, who had significantly greater microbiological isolation, gave support to cervical culture before referral to colposcopy, if such a service was limited. The postmenopausal women had higher isolations of vaginal pathogens, and an inexplicably high isolation rate of group B Streptococci. Surprisingly HRT did not reduce this reservoir of vaginal pathogens. Having data available on both isolation and serology for the same patients, allowed closer examination of trends in Chlamydial infection with age. The conclusion from this evidence, is either that C. trachomatis is not detectable by the microimmunofluoresence technique in advancing age, or this organism is considerably more prevalent now, than in the past. This may still be a co-factor to HPV or smoking, in the genesis of carcinoma,in the younger woman with the aggressive tumour. The final section of the work, has attempted to provide some explanation, for the difficulty in visualisation of the squamo-columnar junction (SCJ), that often accompanies age. Decreased cervical water, at the area around the SCJ was found. Hydroxyproline estimation suggests, that collagen is present in greater density, near the SCJ, in the older woman. The collagen content in the cervical stromal core, however, appears similar at all ages. A histological study, confirms increasing collagen density near the SCJ, with advancing age. HRT may increase cervical water, which may render the SCJ visible, by allowing greater eversion of the endocervix. This study found no effect on collagen by HRT. It has been the aim of this work, to show the cervix in the older woman is different from that in the younger woman. The differences are in appearance, structure, microbiology, and prior vaginal pathogens. The differences may affect the ability to detect cervical neoplasia, and question whether cervical cancer in such older women, is truly the same disease as that in women of childbearing years.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available