644
Cervical Neoplasia and the Pill SINCE the epithelium of the cervix uteri’is a get tissue for steroid
sex
tar-
hormones, oral contracep-
tives are unlikely to be completely without effects upon the development of cervical carcinoma. It is therefore important to discover whether they operate for good or ill, and the magnitude of any demonstrable effect. The fact that massive use of the
.
The difference is significant, but based upon small numbers. No mention is made of any case progressing to invasion. The inference that the pill increases the chance of progression towards cancer is not, however, inescapable. The severity of dysplasia is defined by the extent of loss of surface maturation. Carcinoma-insitu, by definition, has none at all. Progestagens, as used in oral contraceptives, strikingly diminish epithelial maturation in the normal cervix, and this is shown in smears by a reduced karyopyknotic index. There is no reason why a similar effect should not occur in the supposedly precancerous states. Lesions with surface maturation are not necessarily any less precancerous than those without; indeed, invasive carcinoma is often well differentiated. Accordingly, the so-called conversion from dysplasia to carcinoma-in-situ need not mean much in terms of danger to life. Another explanation of the findings is based on the fact that the epithelial lesion, if extensive, usually shows considerable variation from place to place in the same cervix, with more squamous maturation distally, and less maturation further up in the endocervical canal. Since oral contraceptives tend to cause eversion of the endocervix, a small biopsy is more likely to hit an area of carcinoma-in-situ if the patient is on the pill. That progression from dysplasia towards invasive carcinoma is enhanced by contraceptive steroids is therefore only one of several explanations of the Los Angeles data, though still a perfectly plausible one. SINGER and JORDAN9 have tried to exonerate the pill, maintaining firstly, that there is no association between oral contraceptives and cervical atypias, and secondly, if there is, "the pill itself should not be blamed". The verdict may be appropriate according to the Law of England, but the rules of science require the accused to remain in the dock. Even if oral contraceptives do eventually turn out to cause a slightly enhanced risk of cervical carcinogenesis, there is still no need to panic. A cervical smear every 3 or 5 years will readily detect dysplasia or carcinoma-in-situ, which can then be eliminated without loss of cervical function. Carcinoma of the cervix is just as preventable in those who use the pill as in those who do not.
pill.
pill has been accompanied almost everywhere by falling death-rates for cervical cancer should not lead to complacency,’ since most of the women dying of cancer belong to much older age-groups than those consuming the pill. In 1969 a report from New York’ suggested that pill users had an increased prevalence of epithelial abnormalities classified as dysplasia and carcinoma-in-situ, compared with those using the diaphragm. Evaluation was complicated by the possibility of a protective effect of the diaphragm, as well as by the fact that the choice of contraceptives varies in groups of women according to factors that influence the likelihood of cervical carcinoma.2 Some other retrospective studies of matched groups showed no significant association,3,4 nor did a further prospective study from New York. There are numerous other inconclusive papers on this subject.6 Because women coming for contraceptive advice often know what they want, random allocation is no longer possible, but this was done in the original studies from Puerto Rico. Since the pill women and the controls - had frequent cervical smears, carcinoma of the cervix was presumably not allowed to develop, but limited data have been published7 on the changes in grading of smear reports over observation periods said to extend up to 8 years, and no deleterious effect of the pill was noted. ELIZABETH STERN and her colleagues in Los Angeles8 have now published the results of a large prospective study of women attending family-planning clinics between 1967 and 1971, to see whether existing cervical dysplasia tended to run a different course in women using oral contraceptive steroids. 300 cases of dysplasia were found, and followed up by means of repeated smears and annual small biopsies. The average age was 23. Dysplasia frequently regressed during the first six months of observation, and regression was slightly more frequent in pill users; but in those with persistent lesions an increase in severity, and progression to carcinoma-in-situ, was commoner in users of the 1. Melamed, M.
R., Koss, L. G., Flehinger, B. J., Kelisky, R. P., Dubrow, H. J. 1969, iii, 195. 2. Dubrow, H., Melamed, M. R., Flehinger, B. J., Kelisky, R. P., Koss, L. G. Obstet. Gynec. Survey, 1969, 24, 1012. 3. Worth, A. J., Boyes, D. A. J. Obstet. Gynec. Br. Commonw. 1972, 79, 673. 4. Thomas, D. B. Obstet. Gynec. 1972, 40, 508. 5. Melamed, M. R., Flehinger, B. J. Gynec. Oncol. 1973, 1, 290. Br. med.
6. I.A.R.C. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man: no. 6, Sex Hormones; p. 223. Lyon, 1974. 7. Fuertes-de la Haba, A., Pelegrina, L., Bangdiwala, I. S., Hernándes-Cibes, J. J. J. reprod. Med. 1973, 10, 3. 8. Stern, E., Forsythe, A. B., Youkeles, L., Coffelt, C. F., Science, 1977, 196, 1460.
SOME CONSEQUENCES OF BEING BORN TOO SOON OR BORN TOO SMALL deserves its reputation as the best infant in some pregnancies fetal nutrition falters but incubator, and the syndrome of placental insufficiency ensues. The result is a stillbirthor a light-for-dates infant (who faces such immediate dangers as perinatal asphyxia, meconium aspiration, and hypoglycsemia). Now that fetal health and growth can be monitored by biochemical and ultrasonic methods, placental insufficiency may THE
uterus
9. Singer, A.,
Jordan, J. A. Lancet, 1977, ii, 359.
Cervical Neoplasia and the Pill SINCE the epithelium of the cervix uteri’is a get tissue for steroid
sex
tar-
hormones, oral contracep-
tives are unlikely to be completely without effects upon the development of cervical carcinoma. It is therefore important to discover whether they operate for good or ill, and the magnitude of any demonstrable effect. The fact that massive use of the
.
The difference is significant, but based upon small numbers. No mention is made of any case progressing to invasion. The inference that the pill increases the chance of progression towards cancer is not, however, inescapable. The severity of dysplasia is defined by the extent of loss of surface maturation. Carcinoma-insitu, by definition, has none at all. Progestagens, as used in oral contraceptives, strikingly diminish epithelial maturation in the normal cervix, and this is shown in smears by a reduced karyopyknotic index. There is no reason why a similar effect should not occur in the supposedly precancerous states. Lesions with surface maturation are not necessarily any less precancerous than those without; indeed, invasive carcinoma is often well differentiated. Accordingly, the so-called conversion from dysplasia to carcinoma-in-situ need not mean much in terms of danger to life. Another explanation of the findings is based on the fact that the epithelial lesion, if extensive, usually shows considerable variation from place to place in the same cervix, with more squamous maturation distally, and less maturation further up in the endocervical canal. Since oral contraceptives tend to cause eversion of the endocervix, a small biopsy is more likely to hit an area of carcinoma-in-situ if the patient is on the pill. That progression from dysplasia towards invasive carcinoma is enhanced by contraceptive steroids is therefore only one of several explanations of the Los Angeles data, though still a perfectly plausible one. SINGER and JORDAN9 have tried to exonerate the pill, maintaining firstly, that there is no association between oral contraceptives and cervical atypias, and secondly, if there is, "the pill itself should not be blamed". The verdict may be appropriate according to the Law of England, but the rules of science require the accused to remain in the dock. Even if oral contraceptives do eventually turn out to cause a slightly enhanced risk of cervical carcinogenesis, there is still no need to panic. A cervical smear every 3 or 5 years will readily detect dysplasia or carcinoma-in-situ, which can then be eliminated without loss of cervical function. Carcinoma of the cervix is just as preventable in those who use the pill as in those who do not.
pill.
pill has been accompanied almost everywhere by falling death-rates for cervical cancer should not lead to complacency,’ since most of the women dying of cancer belong to much older age-groups than those consuming the pill. In 1969 a report from New York’ suggested that pill users had an increased prevalence of epithelial abnormalities classified as dysplasia and carcinoma-in-situ, compared with those using the diaphragm. Evaluation was complicated by the possibility of a protective effect of the diaphragm, as well as by the fact that the choice of contraceptives varies in groups of women according to factors that influence the likelihood of cervical carcinoma.2 Some other retrospective studies of matched groups showed no significant association,3,4 nor did a further prospective study from New York. There are numerous other inconclusive papers on this subject.6 Because women coming for contraceptive advice often know what they want, random allocation is no longer possible, but this was done in the original studies from Puerto Rico. Since the pill women and the controls - had frequent cervical smears, carcinoma of the cervix was presumably not allowed to develop, but limited data have been published7 on the changes in grading of smear reports over observation periods said to extend up to 8 years, and no deleterious effect of the pill was noted. ELIZABETH STERN and her colleagues in Los Angeles8 have now published the results of a large prospective study of women attending family-planning clinics between 1967 and 1971, to see whether existing cervical dysplasia tended to run a different course in women using oral contraceptive steroids. 300 cases of dysplasia were found, and followed up by means of repeated smears and annual small biopsies. The average age was 23. Dysplasia frequently regressed during the first six months of observation, and regression was slightly more frequent in pill users; but in those with persistent lesions an increase in severity, and progression to carcinoma-in-situ, was commoner in users of the 1. Melamed, M.
R., Koss, L. G., Flehinger, B. J., Kelisky, R. P., Dubrow, H. J. 1969, iii, 195. 2. Dubrow, H., Melamed, M. R., Flehinger, B. J., Kelisky, R. P., Koss, L. G. Obstet. Gynec. Survey, 1969, 24, 1012. 3. Worth, A. J., Boyes, D. A. J. Obstet. Gynec. Br. Commonw. 1972, 79, 673. 4. Thomas, D. B. Obstet. Gynec. 1972, 40, 508. 5. Melamed, M. R., Flehinger, B. J. Gynec. Oncol. 1973, 1, 290. Br. med.
6. I.A.R.C. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man: no. 6, Sex Hormones; p. 223. Lyon, 1974. 7. Fuertes-de la Haba, A., Pelegrina, L., Bangdiwala, I. S., Hernándes-Cibes, J. J. J. reprod. Med. 1973, 10, 3. 8. Stern, E., Forsythe, A. B., Youkeles, L., Coffelt, C. F., Science, 1977, 196, 1460.
SOME CONSEQUENCES OF BEING BORN TOO SOON OR BORN TOO SMALL deserves its reputation as the best infant in some pregnancies fetal nutrition falters but incubator, and the syndrome of placental insufficiency ensues. The result is a stillbirthor a light-for-dates infant (who faces such immediate dangers as perinatal asphyxia, meconium aspiration, and hypoglycsemia). Now that fetal health and growth can be monitored by biochemical and ultrasonic methods, placental insufficiency may THE
uterus
9. Singer, A.,
Jordan, J. A. Lancet, 1977, ii, 359.
