- Email: [email protected]
Cervical carcinoma in women aged 34 and younger
Falcone and Ferenczy
3. 4. 5. 6. 7. 8. 9. 10.
controversies III cancer treatment. Boston: GK Hall 1981:137. Hatch KD, Shingleton HM, AutinJMJr, Soong S-J, Bradley DH. Cryosurgery of CIN. Obstet Gynecol 1981;57: 692. Ostergard DR. Cryosurgery treatment of CIN. Obstet Gynecol 1980;56:231. Creasman WT, Hinshaw WM, Clarke-Pearson DL. Cryosurgery in the management of CIN. Obstet Gynecol 1984;63: 145. Baggish MS. Management of CIN by CO 2 laser. Obstet Gynecol 1982;60:378. Anderson MC. Treatment of CIN with the CO2 laser: report of 543 patients. Obstet Gynecol 1982;59:720. Coppleson LW, Brown B. Estimation of the screening error rate from the observed detection rates in repeated cervical cytology. AM J OBSTET GYNECOL 1974; 119:953. Kolstad P, Stafl A. Atlas of colposcopy, 2d ed. London: University Park Press, 1977. Winkler BW, Crum CP, Fujii T, et al. Koilocytotic lesions
February, 1986 Am J Obstet Gynecol
11. 12. 13. 14. 15. 16.
of the cervix: the relationship of mitotic abnormalities to the presence of papilloma virus antigens and nuclear DNA content. Cancer 1984;53:1081. Cervical cancer screening programs: summary of 1982 Canadian Task report. Can Med AssocJ 1982;127:581. Richart RM, Barron BA. Screening strategies for cervical cancer and cervical intraepithelial neoplasia. Cancer 1981 ;47: 1176. Paterson MEL, Peel KR, Joslin CAF. Cervical smear histories of 500 women with invasive cervical cancer in Yorkshire. Br Med J 1984;289:896. Richart RM, Valliant HW. Influence of cell collection techniques upon cytological diagnosis. Cancer 1965;18:1474. Benedet JL, Anderson CH, Simpson ML, Shaw D. Colposcopy, conization and hysterectomy practices: a current perspective. Obstet Gynecol 1982;60:539. Boyes DA, Worth AJ, Fidler HK. The results of 4389 cases of pre-clinical cervical squamous cell carcinoma. J Obstet Gynaecol Br Communw 1970;77:769.
Cervical carcinoma in women aged 34 and younger J.
A. Carmichael, M.D., C.M., D. H. Clarke, B.Se., M.D., D. Moher, B.A., I. D. Ohlke, R.N., and E. J. Karehmar, B.A. Kingston, Ontario, Canada This presentation addresses three questions concerning invasive cervical carcinoma in women 34 years of age and younger. Is there an increase in the incidence of the disease? Is it more or less susceptible to prevention by cervical screening? Is the clinical behavior different for this age group? Three separate studies are reported: (1) Incidence data in the younger age group have been reviewed at the national, provincial, and local levels. (2) Cytologic screening histories of 125 patients who subsequently developed cervical carcinoma were reviewed. (3) The clinical histories of 121 women 34 years of age and younger, with invasive cervical carcinoma, were reviewed and compared with those of 242 control women 35 years of age and older. Results indicate an increase in incidence in the younger age group in the three prairie provinces only. Cytologic histories are similar except for an increase in false negative reports in the younger age group. Clinical behavior of the disease is similar for both age groups. (AM J OBSTET GYNECOL 1986;154:264-9.)
Key words: Cervical carcinoma, screening, cytologic results There has been a general impression that the incidence of invasive cervical carcinoma in women 34 years of age and younger is increasing. \-3 Other observations in the literature suggest that younger women might be less susceptible to prevention of invasive cervical carcinoma by cervical screening." 5 There is also a develFrom the Departments of Obstetrics and Gynaecology and Community Health and Epidemiology, Queen's University. Supported in part by the Clare Nelson Fund of the Kingston General Hospital. Presented at the Forty-first Annual Meeting of The Society of Obstetricians and Gynaecologists of Canada, Jasper, Alberta, Canada, June 10-15,1985. Reprint requests: Dr. J. A. Carmichael, Department of Obstetrics and Gynaecology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
264
oping concern that the preinvasive disease is more aggressive and reaches the invasive stage more quickly in the younger age group.5.7 This presentation attempts to answer these questions by reviewing three separate patient groups: Group I, incidence data at the national, provincial, and local levels of the invasive disease in women 34 years of age and younger; Group 2, cytologic data consisting of screening histories of women 34 years of age and younger as compared with those of women 35 years of age and older, all of whom subsequently developed invasive cervical carcinoma; Group 3, clinical data consisting of the clinical patterns of the disease in younger and older women treated at the Ontario Cancer Treatment and Research Foundation, Kingston clinic.
Cervical carcinoma 265
Volume 154 Number 2
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1970
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______
1975
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1980
~
1983
Fig. 1. Proportion of women 34 years old and younger, diagnosed as having invasive cervical carcinoma.
0:: W
20
Q.
10
Material and methods
Group 1 Incidence data. These data include the national and provincial age-adjusted incidence rates of invasive cervical carcinoma obtained for the years 1971, 1975, and 1980 from the Ontario Cancer Treatment and Research Foundation, Toronto. Incidence data were also obtained from two local centers (Princess Margaret Hospital, Toronto, and the Ontario Cancer Treatment and Research Foundation, Kingston clinic). Group 2 Cytologic data. These data were based on the cytologic histories of 125 consecutive patients with invasive cervical carcinoma registered at the Ontario Cancer Treatment and Research Foundation, Kingston clinic, between January, 1973, and December, 1984. Thirty-five of these patients were 34 years of age and younger and the remaining 90 patients were 35 years of age and older. At the time of diagnosis both younger and older patients underwent a detailed interview of past cytologic screening. The patients' prior physicians were contacted requesting information on the patient's past cytologic screening, dates of examinations, cytologic reports, and laboratories used. When available, previous cytologic slides were reviewed by our cytopathologist. Information sought from this review included the frequency of undercalled and overcalled cytologic results, differences in response by physicians and/or patients to abnormal cytologic results, and the number of negative cytologic smears obtained prior to the onset of invasive disease.
Group 3 Clinical data. From 1950 to 1984 inclusive, 121 women 34 years of age and younger were treated for invasive cervical carcinoma at the Ontario Cancer Treatment and Research Foundation, Kingston clinic. Their histories beginning at the time of diagnosis of
IA
18
3
4
Fig. 2. The stage (International Federation of Gynecology and Obstetrics) distribution of invasive cervical carcinoma among women ,,;;34 or >34 years of age who had had at least one negative cytologic smear within 3 years before the diagnosis.
the invasive disease were reviewed. A control group of 242 patients 35 years of age and older with invasive cervical carcinoma treated during the same time period were similarly reviewed. For each case there were two controls, the patient with invasive cervical carcinoma, 35 years of age and older, registered immediately before and immediately after the 34-year-old and younger patient. The review of the history included cell type, degree of differentiation, stage, method of treatment, response to treatment, and survival. Accuracy in data collection was assessed after each group of 10 charts when the authors exchanged charts and data recording sheets with each other for review. Univariate analysis comparing younger and older women on all cytologic and clinical data collected was made with the use of X" analysis and t tests. The survival of younger and older women was assessed by the lifetable method of analysis. Results
Group 1 Incidence data. The age-adjusted incidence rates of invasive cervical carcinoma for women 34 years of age and younger indicate little change at the national level during the last decade. The age-adjusted incidence rate changed from 4.0 I cases per 100,000 in 1971 to 3.71
266 Carmichael et al.
February, 1986 Am J Obstet Gynecol
Table I. Age-adjusted incidence rate of cervical carcinoma in women 34 years of age and younger (per 100,000 population) in Canada and the provinces, 1971, 1975, and 1980* 1971 Province
Mean
Canadat Canada Newfoundland Prince Edward Island Nova Scotia New Brunswick Quebec Ontario Manitoba Saskatchewan Alberta British Columbia
I
1975 SE
Mean
3.10 4.01 5.17
0.28 0.25 1.95
3.39 5.01 2.60 5.65 3.03 1.35 2.49 4.89
1.28 1.77 0.37 0.50 1.07 0.78 0.72 0.88
I
1980 SE
Mean
3.24 3.39 6.82
0.26 0.21 2.01
2.33 4.35 1.19 3.77 7.28 3.21 2.82 6.61
0.96 1.46 0.24 0.37 1.53 1.14 0.69 0.78
3.97 3.71 2.37 2.39 3.81 3.96 3.39 3.10 8.94 4.90 3.09 4.22
I
SE
0.27 0.21 1.07 2.41 1.16 1.27 0.39 0.31 1.59 1.28 0.61 0.67
Special thanks to Dr. E. A. Clarke and Ms. R. Dolinsky of the Ontario Cancer Treatment and Research Foundation, Toronto, for preparation of the age-adjusted incidence rates. *Rates are age-adjusted with the world population used as a standard. tCanada does not include Ontario, the Yukon, or Northwest Territories.
Table II. Additional cytologic information addressed in the analysis of the patients' past cytologic screening history Younger group (35 patients*) Variable
No.
Women appropriately screenedt Women with one or more undercalled cytologic smear:j: Women with one or more overcalled cytologic smear:j:
27 20 31
I
Older group (90 patients)
%
No.
79.4 58.8§ 91.211
64 33 86
I
% 71.1 36.7 95.6
*Missing data from one patient. tTwo or more smears within 5 years, three or more smears within 10 years, excluding smears within 3 months of the patient's anniversary date. :j:According to the classification mild, moderate, and severe dysplasia and carcinoma in situ a slide was considered undercalled when the original diagnosis was at least two levels less than that of the reviewing cytopthologist. A slide was considered overcalled when the original diagnosis was at least two levels greater than that of the reviewing cytopathologist. §x'Analysis = 4.09 with I df, P < 0.05. Ilx' Analysis = 0.26 with I df, P < 0.61.
cases per 100,000 in 1980 (Clarke AE, personal communication). However, at the provincial level increases in age-adjusted incidence rates have taken place in the three prairie provinces (Manitoba, Saskatchewan, and Alberta, Table I). In Ontario, the age-adjusted incidence rate indicated a decrease during the last decade. Incidence data collected from two local centers (Princess Margaret Hospital, Toronto, and the Ontario Cancer Treatment and Research Foundation, Kingston clinic) indicate that, of all invasive cervical carcinoma cases reported since 1960, there has been an increase in the proportion of women 34 years of age and younger (Fig. 1). However, from 1975, this increase was more apparent, from 6.8% in 1975 up to 13.6% in 1983.
Group 2 Cytologic data. All 125 women whose cervical cytologic
history was reviewed, between 1973 and 1984, had at least one negative cytologic smear within 10 years of the diagnosis of the invasive disease. Twenty-five (71.4%) younger women and 55 (61.1 %) older women had at least one negative cytologic smear within 3 years preceding the diagnosis of the invasive disease. This difference was not significant (X 2 analysis = 0.8 with 1 df, P = 0.38). The relationship between stage of invasive disease and at least one negative cytologic smear within 3 years before the diagnosis of invasive disease, for younger and older women, is presented in Fig. 2. Younger women having at least one negative cytologic smear within 3 years preceding the diagnosis of invasive disease presented with a less advanced stage as compared with that in older women but this relationship was not significant (X' analysis = 4.46 with 3 df, P = 0.22).
Cervical carcinoma 267
Volume 154 Number 2
Table III. The distribution of stage of invasive cervical carcinoma for younger and older women at the time of diagnosis Younger women
I
No.
Stage*
Older women
13 65 22 16 2 3
IA IB II III
IV Not staged
%
No.
10.7 53.7 18.2 13.2 1.7 2.5
12 92 72 48 15 3
I
% 5.0 38.0 29.8 19.8 6.2 1.2
*x 2 Analysis = 19.0 with 5 df, P < 0.002.
Table IV. The distribution of cell type of invasive cervical carcinoma for younger and older women at the time of diagnosis Younger women
*l
Cell type*
No.
Squamous cell carcinoma Adenocarcinoma Adenocarcinoma-squamous cell carcinoma Undifferentiated small cell carcinoma Undifferentiated large cell carcinoma
III 9 I
I
o
Older women
%
No.
91.7 7.4 0.8
218
I
90.1 9.1 0.4 0.4
22 I I
o
%
o
Analysis = 1.03 with 3 df, P = 0.8.
Table V. The distribution of degree of differentiation of invasive cervical carcinoma for cases and controls at the time of diagnosis Younger women Degree of differentiation*
Well differentiated Moderately differentiated Poorly differentiated Not stated
No.
17
22 28 54
I
Older women
%
No.
14.0 18.2 23.1 44.6
22 53 50 117
I
% 9.1 21.9 20.7 48.3
*x 2 Analysis = 2.86 with 3 df, P = 0.41.
Several additional questions regarding cytologic history in younger and older women were analyzed. Table II indicates the three main additional questions addressed by the cytologic data. The results indicate no significant differences between the two age groups in their cytologic history except that in younger women, compared with older women, the cytologic test results were significantly more likely to be undercalled (X 2 analysis = 4.09 with 1 df, P < 0.04). Group 3 Clinical data. The third part of the analysis examined data collected on the clinical behavior of the invasive disease in younger women (cases) and older women (controls) registered at the Ontario Cancer Treatment and Research Foundation, Kingston clinic, between 1950 and 1984. The mean age of the younger women was 30.2 (SE = 0.31) years and for older women 54.4 (SE = 0.86) years. The results in Table III indicate
a significant difference between younger and older women for stage of disease (X 2 analysis = 19.0 with 5 df, P < 0.002). Seventy-eight (64.5%) younger women and 104 (43.0%) older women presented with Stage I invasive disease, whereas 18 (14.9%) younger and 63 (26%) older women presented with Stage III or IV invasive disease. Younger and older women presented with similar cell types and cell differentiation (Tables IV and V). Younger women differed significantly from older women in their treatment (X 2 analysis = 37.12 with 5 df, P < 0.0001). Younger women in the early stages tended to be treated by surgery significantly more often than the older patients with similar stages. Overall survival for younger and older women is presented in Fig. 3. The results indicate a significant difference between younger and older women in prognosis, younger women having a better prognosis than
268
Carmichael et al.
February, 1986 Am J Obstet Gynecol
~
0
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>
>.
:0 0 .0
e
::3
(f)
40 30 20 10
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0
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20
25
°
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Fig. 5. Overall survival of younger and older women with Stage IB carcinoma treated by operation.
0
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:;
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Fig. 3. Overall survival of all younger and older patients with invasive cervical carcinoma.
a..
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C
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(n=86) 10
15
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Years
Fig. 4. Overall survival of younger and older women for all stages of invasive cervical carcinoma.
Fig. 6. Overall survival of younger and older women with Stage IB carcinoma who underwent pelvic irradiation.
older women. Stage-by-stage survival is presented in Fig. 4. The results indicate no significant difference between younger and older women. Finally, shown in Figs. 5 and 6 is the prognosis for younger and older women diagnosed as having Stage IB invasive disease who underwent radical hysterectomy or radiation treatment. The results indicate no significant differences in prognosis by either mode of treatment between vounger and older women.
overcalled cytologic results, and the time between the last negative cytologic smear and the diagnosis of invasive disease. Also, the stage distribution between younger and older women was similar. These findings are in contrast to observations made in the literature that indicate that younger women may be less susceptible to a screening program and that the natural history of the preinvasive disease may be shorter in this age group. 1.",.7 If younger women had a shorter preinvasive period it might be expected that they would present with a more advanced stage of disease. Fig. 2 shows this not to be the case, that is, when younger and older women had a negative smear within 3 years of diagnosis of the invasive disease the stage distribution was similar. The single difference in the cytologic screening histories betwen younger and older women is the significant increase in undercalled cytologic reports in younger women. This finding is difficult to explain but has been reported elsewhere. 7 Group 3 Clinical data. Analysis of the clinical histories of the 363 women with invasive cervical carcinoma treated at the Ontario Cancer Treatment and Research Foundation, Kingston clinic, show that women 34 years of age and younger have a less advanced stage than women 35 years of age and older. This simply reflects the increased screening activity in the younger population." The result of which is to lower the overall staging in the younger age group."
Comment
Group 1 Incidence data. The results from the present study indicate little change in the age-adjusted incidence rates for Canada during the last decade. Increases were noted in the three prairie provinces. Provincial variation is difficult to explain but may be due in part to variation in screening activities and registration systems between the provinces. Despite the national experience, incidence data collected from the two local centers indicated an increase in the proportion of women 34 years of age and younger diagnosed as having invasive cervical carcinoma, particularly during the last decade. Group 2 Cytologic data. The cytologic histories of younger and older screened women indicated no significant difference in appropriateness of screening (for instance, the frequency of cytologic examination and appropriate response to abnormal cytologic report), frequency of
Cervical carcinoma
Volume 154 Number 2
The present study indicated a difference in overall survival between younger and older women, which can be explained simply on the basis of more younger women presenting with invasive disease in the earlier stages. The survival patterns are similar, stage by stage, for younger and older women. Different treatment modalities between younger women and older women with less advanced invasive disease in favor of surgery for younger women is an expression of the general trend to treat less advanced invasive disease, in this age group, with operation rather than radiation. However, when survival patterns are compared between younger and older women with Stage IB disease, survival patterns with radical hysterectomy treatment and radiation are similar for both age groups. Thus neither treatment modality favors younger women. It is our opinion, on the basis of the present review, that there has been a recent slight increase in the proportion of younger women diagnosed as having invasive cervical carcinoma. The susceptibility to a screening program, the natural history of the disease, and the response to treatment are similar for younger and older women.
REFERENCES I. Walton RJ, Allen HH, Anderson, GH, et al. Cervical cancer
screening programs. Can Med AssocJ 1982;127:581. 2. Bourne RG, Grove WD. Invasive carcinoma of the cervix in Queensland. MedJ Aust 1983;1:156. 3. Green GH. Cervical cancer and cytology screening in New Zealand. Br J Obstet Gynaecol 1978;85:818. 4. Berkeley AS, LiVolsi VA, Schwartz PE. Advanced squamous cell carcinoma of the cervix with recent normal Papanicoulaou tests. Lancet 1980;2:375. 5. Rylander E. Negative smears in women developing invasive cervical cancer. Acta Obstet Gynecol Scand 1977;56:115. 6. Prempree T, Patanaphan V, Sewchand W, et al. The influence of patients' age and tumor grade on the prognosis of carcinoma of the cervix. Cancer 1983;51: 1764. 7. Paterson MEL, Peel KR, Joslin CAF. Cervical smear histories of 500 women with invasive cervical cancer in Yorkshire. Br Med J 1984;289:896. 8. Carmichael JA, Jeffrey JF, Steele HD, et al. The cytologic history of 245 patients developing invasive cervical carcinoma. AM J OBSTET GVNECOL 1984; 148:685. 9. Walton RJ, Blanchet M, Boyes DA, et al. Cervical cancer screening programs (Department of National Health and Welfare Task Force Report). Can Med Assoc J 1976;114:1003.
Biophysical profile scoring in the management of the postterm pregnancy: An analysis of 307 patients J. M. Johnson, M.D., C. R. Harman, M.D., I. R. Lange, M.D., and F. A. Manning, M.D. Winnipeg, Manitoba, Canada Management and outcome were reviewed in 307 consecutive postterm pregnancies assessed by biophysical profile scoring. Twice-weekly scores accurately differentiated normal fetuses from those at risk for intrauterine hypoxia. When the profile score is normal, waiting for spontaneous labor results in healthy neonates and a much lower cesarean section rate (15% versus 42% for "prophylactic" induction). Confident conservative management of postterm pregnancy is possible. (AM J OSSTET GVNECOL 1986;154:269-73.)
Key words: Postterm pregnancy, biophysical profile scoring Pregnancy persisting beyond 42 weeks of gestation or 294 days from the first day of the last normal menFrom the Division of Maternal-Fetal Medicine, Department of Obstetrics, G.vnecology, and Reproductive Sciences, University of Manitoba. Presented at the Forty-first Annual Meeting of The Society of Obstetricians and G.vnaecologists of Canada, Jasper, Alberta, Canada, June 10-15, 1985. Reprinl reque.5t.5: Dr. C. R. Harman, Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, Women's HO.5pital, 735 Notre Dame Ave., WinniPeg, Manitoba, Canada R3E OL8.
strual period is considered postterm and occurs in approximately 10% of all pregnancies.' Postterm pregnancy is associated with an increase in perinatal mortality, meconium-stained liquor, fetal distress in labor, and subsequent development and behavioral disturbances." Although it is a common problem, there is no unanimity of opinion regarding optimal management. Previous studies have reached little agreement as to when fetal jeopardy begins, how accurately the most endangered fetuses can be detected, or whether safe limits
269
3. 4. 5. 6. 7. 8. 9. 10.
controversies III cancer treatment. Boston: GK Hall 1981:137. Hatch KD, Shingleton HM, AutinJMJr, Soong S-J, Bradley DH. Cryosurgery of CIN. Obstet Gynecol 1981;57: 692. Ostergard DR. Cryosurgery treatment of CIN. Obstet Gynecol 1980;56:231. Creasman WT, Hinshaw WM, Clarke-Pearson DL. Cryosurgery in the management of CIN. Obstet Gynecol 1984;63: 145. Baggish MS. Management of CIN by CO 2 laser. Obstet Gynecol 1982;60:378. Anderson MC. Treatment of CIN with the CO2 laser: report of 543 patients. Obstet Gynecol 1982;59:720. Coppleson LW, Brown B. Estimation of the screening error rate from the observed detection rates in repeated cervical cytology. AM J OBSTET GYNECOL 1974; 119:953. Kolstad P, Stafl A. Atlas of colposcopy, 2d ed. London: University Park Press, 1977. Winkler BW, Crum CP, Fujii T, et al. Koilocytotic lesions
February, 1986 Am J Obstet Gynecol
11. 12. 13. 14. 15. 16.
of the cervix: the relationship of mitotic abnormalities to the presence of papilloma virus antigens and nuclear DNA content. Cancer 1984;53:1081. Cervical cancer screening programs: summary of 1982 Canadian Task report. Can Med AssocJ 1982;127:581. Richart RM, Barron BA. Screening strategies for cervical cancer and cervical intraepithelial neoplasia. Cancer 1981 ;47: 1176. Paterson MEL, Peel KR, Joslin CAF. Cervical smear histories of 500 women with invasive cervical cancer in Yorkshire. Br Med J 1984;289:896. Richart RM, Valliant HW. Influence of cell collection techniques upon cytological diagnosis. Cancer 1965;18:1474. Benedet JL, Anderson CH, Simpson ML, Shaw D. Colposcopy, conization and hysterectomy practices: a current perspective. Obstet Gynecol 1982;60:539. Boyes DA, Worth AJ, Fidler HK. The results of 4389 cases of pre-clinical cervical squamous cell carcinoma. J Obstet Gynaecol Br Communw 1970;77:769.
Cervical carcinoma in women aged 34 and younger J.
A. Carmichael, M.D., C.M., D. H. Clarke, B.Se., M.D., D. Moher, B.A., I. D. Ohlke, R.N., and E. J. Karehmar, B.A. Kingston, Ontario, Canada This presentation addresses three questions concerning invasive cervical carcinoma in women 34 years of age and younger. Is there an increase in the incidence of the disease? Is it more or less susceptible to prevention by cervical screening? Is the clinical behavior different for this age group? Three separate studies are reported: (1) Incidence data in the younger age group have been reviewed at the national, provincial, and local levels. (2) Cytologic screening histories of 125 patients who subsequently developed cervical carcinoma were reviewed. (3) The clinical histories of 121 women 34 years of age and younger, with invasive cervical carcinoma, were reviewed and compared with those of 242 control women 35 years of age and older. Results indicate an increase in incidence in the younger age group in the three prairie provinces only. Cytologic histories are similar except for an increase in false negative reports in the younger age group. Clinical behavior of the disease is similar for both age groups. (AM J OBSTET GYNECOL 1986;154:264-9.)
Key words: Cervical carcinoma, screening, cytologic results There has been a general impression that the incidence of invasive cervical carcinoma in women 34 years of age and younger is increasing. \-3 Other observations in the literature suggest that younger women might be less susceptible to prevention of invasive cervical carcinoma by cervical screening." 5 There is also a develFrom the Departments of Obstetrics and Gynaecology and Community Health and Epidemiology, Queen's University. Supported in part by the Clare Nelson Fund of the Kingston General Hospital. Presented at the Forty-first Annual Meeting of The Society of Obstetricians and Gynaecologists of Canada, Jasper, Alberta, Canada, June 10-15,1985. Reprint requests: Dr. J. A. Carmichael, Department of Obstetrics and Gynaecology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
264
oping concern that the preinvasive disease is more aggressive and reaches the invasive stage more quickly in the younger age group.5.7 This presentation attempts to answer these questions by reviewing three separate patient groups: Group I, incidence data at the national, provincial, and local levels of the invasive disease in women 34 years of age and younger; Group 2, cytologic data consisting of screening histories of women 34 years of age and younger as compared with those of women 35 years of age and older, all of whom subsequently developed invasive cervical carcinoma; Group 3, clinical data consisting of the clinical patterns of the disease in younger and older women treated at the Ontario Cancer Treatment and Research Foundation, Kingston clinic.
Cervical carcinoma 265
Volume 154 Number 2
~ 100I
t-
~~34
O
~
16
Z
14
o
~ o
40
-!::
12
Z
o
~ ~ o
&:
10 8
30
~
6 4
z
2
(,)
w
OL-____-L______L -____ 1960
0>34
1965
1970
~
______
1975
~
__
1980
~
1983
Fig. 1. Proportion of women 34 years old and younger, diagnosed as having invasive cervical carcinoma.
0:: W
20
Q.
10
Material and methods
Group 1 Incidence data. These data include the national and provincial age-adjusted incidence rates of invasive cervical carcinoma obtained for the years 1971, 1975, and 1980 from the Ontario Cancer Treatment and Research Foundation, Toronto. Incidence data were also obtained from two local centers (Princess Margaret Hospital, Toronto, and the Ontario Cancer Treatment and Research Foundation, Kingston clinic). Group 2 Cytologic data. These data were based on the cytologic histories of 125 consecutive patients with invasive cervical carcinoma registered at the Ontario Cancer Treatment and Research Foundation, Kingston clinic, between January, 1973, and December, 1984. Thirty-five of these patients were 34 years of age and younger and the remaining 90 patients were 35 years of age and older. At the time of diagnosis both younger and older patients underwent a detailed interview of past cytologic screening. The patients' prior physicians were contacted requesting information on the patient's past cytologic screening, dates of examinations, cytologic reports, and laboratories used. When available, previous cytologic slides were reviewed by our cytopathologist. Information sought from this review included the frequency of undercalled and overcalled cytologic results, differences in response by physicians and/or patients to abnormal cytologic results, and the number of negative cytologic smears obtained prior to the onset of invasive disease.
Group 3 Clinical data. From 1950 to 1984 inclusive, 121 women 34 years of age and younger were treated for invasive cervical carcinoma at the Ontario Cancer Treatment and Research Foundation, Kingston clinic. Their histories beginning at the time of diagnosis of
IA
18
3
4
Fig. 2. The stage (International Federation of Gynecology and Obstetrics) distribution of invasive cervical carcinoma among women ,,;;34 or >34 years of age who had had at least one negative cytologic smear within 3 years before the diagnosis.
the invasive disease were reviewed. A control group of 242 patients 35 years of age and older with invasive cervical carcinoma treated during the same time period were similarly reviewed. For each case there were two controls, the patient with invasive cervical carcinoma, 35 years of age and older, registered immediately before and immediately after the 34-year-old and younger patient. The review of the history included cell type, degree of differentiation, stage, method of treatment, response to treatment, and survival. Accuracy in data collection was assessed after each group of 10 charts when the authors exchanged charts and data recording sheets with each other for review. Univariate analysis comparing younger and older women on all cytologic and clinical data collected was made with the use of X" analysis and t tests. The survival of younger and older women was assessed by the lifetable method of analysis. Results
Group 1 Incidence data. The age-adjusted incidence rates of invasive cervical carcinoma for women 34 years of age and younger indicate little change at the national level during the last decade. The age-adjusted incidence rate changed from 4.0 I cases per 100,000 in 1971 to 3.71
266 Carmichael et al.
February, 1986 Am J Obstet Gynecol
Table I. Age-adjusted incidence rate of cervical carcinoma in women 34 years of age and younger (per 100,000 population) in Canada and the provinces, 1971, 1975, and 1980* 1971 Province
Mean
Canadat Canada Newfoundland Prince Edward Island Nova Scotia New Brunswick Quebec Ontario Manitoba Saskatchewan Alberta British Columbia
I
1975 SE
Mean
3.10 4.01 5.17
0.28 0.25 1.95
3.39 5.01 2.60 5.65 3.03 1.35 2.49 4.89
1.28 1.77 0.37 0.50 1.07 0.78 0.72 0.88
I
1980 SE
Mean
3.24 3.39 6.82
0.26 0.21 2.01
2.33 4.35 1.19 3.77 7.28 3.21 2.82 6.61
0.96 1.46 0.24 0.37 1.53 1.14 0.69 0.78
3.97 3.71 2.37 2.39 3.81 3.96 3.39 3.10 8.94 4.90 3.09 4.22
I
SE
0.27 0.21 1.07 2.41 1.16 1.27 0.39 0.31 1.59 1.28 0.61 0.67
Special thanks to Dr. E. A. Clarke and Ms. R. Dolinsky of the Ontario Cancer Treatment and Research Foundation, Toronto, for preparation of the age-adjusted incidence rates. *Rates are age-adjusted with the world population used as a standard. tCanada does not include Ontario, the Yukon, or Northwest Territories.
Table II. Additional cytologic information addressed in the analysis of the patients' past cytologic screening history Younger group (35 patients*) Variable
No.
Women appropriately screenedt Women with one or more undercalled cytologic smear:j: Women with one or more overcalled cytologic smear:j:
27 20 31
I
Older group (90 patients)
%
No.
79.4 58.8§ 91.211
64 33 86
I
% 71.1 36.7 95.6
*Missing data from one patient. tTwo or more smears within 5 years, three or more smears within 10 years, excluding smears within 3 months of the patient's anniversary date. :j:According to the classification mild, moderate, and severe dysplasia and carcinoma in situ a slide was considered undercalled when the original diagnosis was at least two levels less than that of the reviewing cytopthologist. A slide was considered overcalled when the original diagnosis was at least two levels greater than that of the reviewing cytopathologist. §x'Analysis = 4.09 with I df, P < 0.05. Ilx' Analysis = 0.26 with I df, P < 0.61.
cases per 100,000 in 1980 (Clarke AE, personal communication). However, at the provincial level increases in age-adjusted incidence rates have taken place in the three prairie provinces (Manitoba, Saskatchewan, and Alberta, Table I). In Ontario, the age-adjusted incidence rate indicated a decrease during the last decade. Incidence data collected from two local centers (Princess Margaret Hospital, Toronto, and the Ontario Cancer Treatment and Research Foundation, Kingston clinic) indicate that, of all invasive cervical carcinoma cases reported since 1960, there has been an increase in the proportion of women 34 years of age and younger (Fig. 1). However, from 1975, this increase was more apparent, from 6.8% in 1975 up to 13.6% in 1983.
Group 2 Cytologic data. All 125 women whose cervical cytologic
history was reviewed, between 1973 and 1984, had at least one negative cytologic smear within 10 years of the diagnosis of the invasive disease. Twenty-five (71.4%) younger women and 55 (61.1 %) older women had at least one negative cytologic smear within 3 years preceding the diagnosis of the invasive disease. This difference was not significant (X 2 analysis = 0.8 with 1 df, P = 0.38). The relationship between stage of invasive disease and at least one negative cytologic smear within 3 years before the diagnosis of invasive disease, for younger and older women, is presented in Fig. 2. Younger women having at least one negative cytologic smear within 3 years preceding the diagnosis of invasive disease presented with a less advanced stage as compared with that in older women but this relationship was not significant (X' analysis = 4.46 with 3 df, P = 0.22).
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Volume 154 Number 2
Table III. The distribution of stage of invasive cervical carcinoma for younger and older women at the time of diagnosis Younger women
I
No.
Stage*
Older women
13 65 22 16 2 3
IA IB II III
IV Not staged
%
No.
10.7 53.7 18.2 13.2 1.7 2.5
12 92 72 48 15 3
I
% 5.0 38.0 29.8 19.8 6.2 1.2
*x 2 Analysis = 19.0 with 5 df, P < 0.002.
Table IV. The distribution of cell type of invasive cervical carcinoma for younger and older women at the time of diagnosis Younger women
*l
Cell type*
No.
Squamous cell carcinoma Adenocarcinoma Adenocarcinoma-squamous cell carcinoma Undifferentiated small cell carcinoma Undifferentiated large cell carcinoma
III 9 I
I
o
Older women
%
No.
91.7 7.4 0.8
218
I
90.1 9.1 0.4 0.4
22 I I
o
%
o
Analysis = 1.03 with 3 df, P = 0.8.
Table V. The distribution of degree of differentiation of invasive cervical carcinoma for cases and controls at the time of diagnosis Younger women Degree of differentiation*
Well differentiated Moderately differentiated Poorly differentiated Not stated
No.
17
22 28 54
I
Older women
%
No.
14.0 18.2 23.1 44.6
22 53 50 117
I
% 9.1 21.9 20.7 48.3
*x 2 Analysis = 2.86 with 3 df, P = 0.41.
Several additional questions regarding cytologic history in younger and older women were analyzed. Table II indicates the three main additional questions addressed by the cytologic data. The results indicate no significant differences between the two age groups in their cytologic history except that in younger women, compared with older women, the cytologic test results were significantly more likely to be undercalled (X 2 analysis = 4.09 with 1 df, P < 0.04). Group 3 Clinical data. The third part of the analysis examined data collected on the clinical behavior of the invasive disease in younger women (cases) and older women (controls) registered at the Ontario Cancer Treatment and Research Foundation, Kingston clinic, between 1950 and 1984. The mean age of the younger women was 30.2 (SE = 0.31) years and for older women 54.4 (SE = 0.86) years. The results in Table III indicate
a significant difference between younger and older women for stage of disease (X 2 analysis = 19.0 with 5 df, P < 0.002). Seventy-eight (64.5%) younger women and 104 (43.0%) older women presented with Stage I invasive disease, whereas 18 (14.9%) younger and 63 (26%) older women presented with Stage III or IV invasive disease. Younger and older women presented with similar cell types and cell differentiation (Tables IV and V). Younger women differed significantly from older women in their treatment (X 2 analysis = 37.12 with 5 df, P < 0.0001). Younger women in the early stages tended to be treated by surgery significantly more often than the older patients with similar stages. Overall survival for younger and older women is presented in Fig. 3. The results indicate a significant difference between younger and older women in prognosis, younger women having a better prognosis than
268
Carmichael et al.
February, 1986 Am J Obstet Gynecol
~
0
"0 >
>
>.
:0 0 .0
e
::3
(f)
40 30 20 10
a..
0
0---0 Younger D--oOlder
0
5
15
10 Years
20
25
°
\
:a 20 0 .0
e
\~'O !I
o Younger DOlder
~
40
.c 0 .c
20
0----0 Younger(n=36)
....0
10
o-a Older
0
5
10 Years
15
20
Fig. 5. Overall survival of younger and older women with Stage IB carcinoma treated by operation.
0
> .:;:
Stage 2
:;
o~
-------0
60
(f)
'0 40 Stage 3and4
I!I
(n = 17)
~
0 0,
00
60
"0 80
~
0 0
0
Stage IA Stage IB
~~-o ~
~
0-
Fig. 3. Overall survival of all younger and older patients with invasive cervical carcinoma.
a..
80
.~
::::J (f)
'0
100
C
.~
20
Yea r s
~
:.c0
20
e
a
.0
a..
0--0
Younger ( n =68 )
0--0
Older 5
(n=86) 10
15
20
Years
Fig. 4. Overall survival of younger and older women for all stages of invasive cervical carcinoma.
Fig. 6. Overall survival of younger and older women with Stage IB carcinoma who underwent pelvic irradiation.
older women. Stage-by-stage survival is presented in Fig. 4. The results indicate no significant difference between younger and older women. Finally, shown in Figs. 5 and 6 is the prognosis for younger and older women diagnosed as having Stage IB invasive disease who underwent radical hysterectomy or radiation treatment. The results indicate no significant differences in prognosis by either mode of treatment between vounger and older women.
overcalled cytologic results, and the time between the last negative cytologic smear and the diagnosis of invasive disease. Also, the stage distribution between younger and older women was similar. These findings are in contrast to observations made in the literature that indicate that younger women may be less susceptible to a screening program and that the natural history of the preinvasive disease may be shorter in this age group. 1.",.7 If younger women had a shorter preinvasive period it might be expected that they would present with a more advanced stage of disease. Fig. 2 shows this not to be the case, that is, when younger and older women had a negative smear within 3 years of diagnosis of the invasive disease the stage distribution was similar. The single difference in the cytologic screening histories betwen younger and older women is the significant increase in undercalled cytologic reports in younger women. This finding is difficult to explain but has been reported elsewhere. 7 Group 3 Clinical data. Analysis of the clinical histories of the 363 women with invasive cervical carcinoma treated at the Ontario Cancer Treatment and Research Foundation, Kingston clinic, show that women 34 years of age and younger have a less advanced stage than women 35 years of age and older. This simply reflects the increased screening activity in the younger population." The result of which is to lower the overall staging in the younger age group."
Comment
Group 1 Incidence data. The results from the present study indicate little change in the age-adjusted incidence rates for Canada during the last decade. Increases were noted in the three prairie provinces. Provincial variation is difficult to explain but may be due in part to variation in screening activities and registration systems between the provinces. Despite the national experience, incidence data collected from the two local centers indicated an increase in the proportion of women 34 years of age and younger diagnosed as having invasive cervical carcinoma, particularly during the last decade. Group 2 Cytologic data. The cytologic histories of younger and older screened women indicated no significant difference in appropriateness of screening (for instance, the frequency of cytologic examination and appropriate response to abnormal cytologic report), frequency of
Cervical carcinoma
Volume 154 Number 2
The present study indicated a difference in overall survival between younger and older women, which can be explained simply on the basis of more younger women presenting with invasive disease in the earlier stages. The survival patterns are similar, stage by stage, for younger and older women. Different treatment modalities between younger women and older women with less advanced invasive disease in favor of surgery for younger women is an expression of the general trend to treat less advanced invasive disease, in this age group, with operation rather than radiation. However, when survival patterns are compared between younger and older women with Stage IB disease, survival patterns with radical hysterectomy treatment and radiation are similar for both age groups. Thus neither treatment modality favors younger women. It is our opinion, on the basis of the present review, that there has been a recent slight increase in the proportion of younger women diagnosed as having invasive cervical carcinoma. The susceptibility to a screening program, the natural history of the disease, and the response to treatment are similar for younger and older women.
REFERENCES I. Walton RJ, Allen HH, Anderson, GH, et al. Cervical cancer
screening programs. Can Med AssocJ 1982;127:581. 2. Bourne RG, Grove WD. Invasive carcinoma of the cervix in Queensland. MedJ Aust 1983;1:156. 3. Green GH. Cervical cancer and cytology screening in New Zealand. Br J Obstet Gynaecol 1978;85:818. 4. Berkeley AS, LiVolsi VA, Schwartz PE. Advanced squamous cell carcinoma of the cervix with recent normal Papanicoulaou tests. Lancet 1980;2:375. 5. Rylander E. Negative smears in women developing invasive cervical cancer. Acta Obstet Gynecol Scand 1977;56:115. 6. Prempree T, Patanaphan V, Sewchand W, et al. The influence of patients' age and tumor grade on the prognosis of carcinoma of the cervix. Cancer 1983;51: 1764. 7. Paterson MEL, Peel KR, Joslin CAF. Cervical smear histories of 500 women with invasive cervical cancer in Yorkshire. Br Med J 1984;289:896. 8. Carmichael JA, Jeffrey JF, Steele HD, et al. The cytologic history of 245 patients developing invasive cervical carcinoma. AM J OBSTET GVNECOL 1984; 148:685. 9. Walton RJ, Blanchet M, Boyes DA, et al. Cervical cancer screening programs (Department of National Health and Welfare Task Force Report). Can Med Assoc J 1976;114:1003.
Biophysical profile scoring in the management of the postterm pregnancy: An analysis of 307 patients J. M. Johnson, M.D., C. R. Harman, M.D., I. R. Lange, M.D., and F. A. Manning, M.D. Winnipeg, Manitoba, Canada Management and outcome were reviewed in 307 consecutive postterm pregnancies assessed by biophysical profile scoring. Twice-weekly scores accurately differentiated normal fetuses from those at risk for intrauterine hypoxia. When the profile score is normal, waiting for spontaneous labor results in healthy neonates and a much lower cesarean section rate (15% versus 42% for "prophylactic" induction). Confident conservative management of postterm pregnancy is possible. (AM J OSSTET GVNECOL 1986;154:269-73.)
Key words: Postterm pregnancy, biophysical profile scoring Pregnancy persisting beyond 42 weeks of gestation or 294 days from the first day of the last normal menFrom the Division of Maternal-Fetal Medicine, Department of Obstetrics, G.vnecology, and Reproductive Sciences, University of Manitoba. Presented at the Forty-first Annual Meeting of The Society of Obstetricians and G.vnaecologists of Canada, Jasper, Alberta, Canada, June 10-15, 1985. Reprinl reque.5t.5: Dr. C. R. Harman, Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, Women's HO.5pital, 735 Notre Dame Ave., WinniPeg, Manitoba, Canada R3E OL8.
strual period is considered postterm and occurs in approximately 10% of all pregnancies.' Postterm pregnancy is associated with an increase in perinatal mortality, meconium-stained liquor, fetal distress in labor, and subsequent development and behavioral disturbances." Although it is a common problem, there is no unanimity of opinion regarding optimal management. Previous studies have reached little agreement as to when fetal jeopardy begins, how accurately the most endangered fetuses can be detected, or whether safe limits
269