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Invasive cervical carcinoma in young women
GYNECOLOGIC
ONCOLOGY
Invasive
8,
311-316 (1979)
Cervical
Ross S. BERKOWITZ, RISA LAVIZZO-MOUREY,
Carcinoma
in Young Women
M.D.. ROBERT L. EHRMANN, M.D., M.D., AND ROBERT C. KNAPP, M.D.’
Division of Gynecologic Oncology of the Department of Obstetrics & Gynecology und the Department of Pathology, Harvard Medical School ctnd the Boston Hospital for Women, Boston, Mussachusetts Received May 8, 1979 Twenty-seven (24.5%) of the 110 newly diagnosed cases of invasive cervical cancer at the Boston Hospital for Women from January 1975 through June 1978 were 35 years of age or younger. Twenty-five of these young patients (93%) had Stage I cervical cancer and 2 had Stage II disease. Seven (26%) of these patients had cervical adenocarcinomas. All young patients with Stage I disease are presently clinically free of tumor. Fifteen of the young patients (55.5%) had reportedly negative cervical cytology smears prior to the detection of a symptomatic cervical malignancy. The cervical smears from 10 of the patients with reportedly negative cervical cytology were reexamined at the Boston Hospital for Women, and our review demonstrated missed cervical neoplasia in 5 cases and unsatisfactory technique for adequate interpretation in 2 cases. Abnormal cervical cytology precipitated the diagnosis of invasive cervical cancer in only 37% of the young patients. All suspicious and symptomatic cervical lesions in young women should be promptly biopsied regardless of prior reassuring cervical cytology.
Although cervical cancer in young women is an infrequent occurrence, it is important to more fully understand the natural history of this disease in young patients. Since the introduction of cytologic screening, the reduction of cervical cancer incidence in the United States has been most marked in young patients [I]. Invasive cervical cancer has been reported under the age of 35 in less than 10% of the population with this diagnosis [2,3]. However, during recent years, we have observed that cervical carcinoma has been frequently diagnosed and treated in our institution in patients under 35 years of age. Reports regarding the natural history of cervical cancer in young patients have led to conflicting conclusions. While some studies suggest a poor prognosis, other authors have found either no difference or even a better prognosis for these patients [2, 4-81. The frequent occurrence of cervical cancer in young women in our institution has provided us an opportunity to investigate the evolution of this disease process. We have been disturbed by the occurrence of sequential reportedly negative ’ Address reprint requests to Robert C. Knapp, M.D., Boston Hospital for Women, Department of Gynecology, 245 Pond Avenue, Brookline, Massachusetts 02146. 311 0090-825817910603 I l-06$0 1.00/O Copyright @ 1979 by Academic Press, Inc. All rights of reproduction in any form reserved.
312
BERKOWITZ
ET AL.
cervical cytology tests in some young patients prior to the detection of invasive cancer. The present study was undertaken to evaluate cervical cancer in patients under the age of 35 regarding stage distribution, histology, natural history, and methods of diagnosis. MATERIALS
AND METHODS
All 110 newly diagnosed cases of invasive cervical cancer at the Boston Hospital for Women from January 1975 through June 1978 were evaluated regarding patient age, race, parity, clinical stage, histologic diagnosis, and therapy. Pathologic specimens from cervical biopsies, hysterectomies, and pelvic lymph node dissections were reviewed by members of the Department of Pathology of the Boston Hospital for Women. The factors that precipitated the diagnosis of invasive cervical cancer were carefully examined in the patients 35 years of age or younger. All cervical cytology reports within 2 years of the diagnosis of invasive cervical cancer were fully reviewed in the young patients. When the prior cervical smears were reported as negative, the slides were requested for reexamination in the cytology laboratory of the Boston Hospital for Women. The cervical smears were reviewed by our cytologic technicians without their knowledge that these patients were diagnosed as having invasive cervical cancer. The smears were analyzed to assess the adequacy of the sample by the degree of cellularity, the fixation and staining quality, and the cytologic diagnosis. RESULTS
Twenty-seven patients (24.5%) of the 110 newly diagnosed cases of invasive cervical cancer were 35 years of age or younger. The youngest patient in the series was 22 years old. Among the 27 young patients, the average age was 29.6 years and the median age was 30 years. Only 1 of the 27 young patients had never been pregnant. The racial distribution of the young patients with cervical cancer was no different from that of the older population. Twenty-five of the 27 young patients with invasive cervical cancer were Caucasian. The distribution of the clinical stage of cervical cancer in relation to age is summarized in Table 1. While only 52% of patients over 35 years of age had Stage I cervical cancer, 93% of patients 35 years of age or younger had Stage I disease (P ~0.05). Two of the patients under 35 had Stage II cervical carcinoma and none had Stage III or IV at initial diagnosis. The relationship of cervical cancer histology to age is outlined in Table 2. Only 8 patients (9.6%) over the age of 35 had adenocarcinoma of the cervix. In contrast, 7 of the 27 patients (26%) who were 35 years of age or younger had cervical adenocarcinoma (P G 0.05). Twenty-four of the 25 young patients with Stage I cervical cancer were treated surgically and one patient was managed with primary radiotherapy. Four of the patients under 35 (16%) had metastatic carcinoma in their pelvic nodes at the time of radical hysterectomy. The sites of pelvic nodal involvement were as follows: one patient had one positive left iliac lymph node, one patient had two positive left iliac lymph nodes, one patient had one positive left obturator lymph node, and one
INVASIVE
CERVICAL
CARCINOMA
TABLE DISTRIBUTION
OF CLINICAL
(years)
Total No. of patients
>35
83
s35
27
Stage
YOUNG
313
WOMEN
1
STAGES
IN RELATION
Age
IN
OF CERVICAL
CANCER
TO AGE
I
Stage
43 (51.8%) 25 (92.6%)
II
29 (35%) 2 (7.4%)
Stage
III
Stage
9 ( 10.8%) 0
IV
2 (2.4%) 0
patient had four positive right iliac and obturator lymph nodes. The parametrial and vaginal tissues were pathologically free of carcinoma in the 24 cases with Stage I disease treated with surgery. All 25 young patients with Stage I cervical cancer are presently clinically free of disease. Three of the four young patients with pelvic nodal metastasis were treated with postoperative radiotherapy. The one patient with involved pelvic nodes, who did not receive irradiation postoperatively, developed a pelvic side wall recurrence 6 months after surgery. This patient was then treated with external beam radiotherapy and currently is free of carcinoma 24 months after her radiation therapy. The two young patients with Stage II-b disease were treated with primary radiotherapy and both subsequently developed pulmonary metastases. One of the two patients has died, while the other is currently being treated with chemotherapy. Twenty-five of the young patients had cervical cytology smears within 2 years of the diagnosis of invasive cervical cancer. Fifteen (55.5%) of the young patients had reportedly negative cervical cytology smears within 2 years of the detection of invasive malignancy. All of these 15 patients were discovered to have a clinically evident cervical lesion only after they presented to their gynecologist with irregular vaginal bleeding, postcoital bleeding, or persistent vaginal discharge. Fourteen of these 15 patients, who presented with symptomatic cervical lesions, were diagnosed as having Stage I-b cervical carcinoma, and the remaining patient had Stage II-b disease. Abnormal cervical cytology was the precipitating factor leading to the diagnosis of cervical cancer in only IO of the young patients (37%). Two young patients, who had prior uninvestigated abnormal cervical smears, presented to their gynecologists with postcoital bleeding due to ulcerative cervical TABLE CERVICAL
Age
CANCER
HISTOLOGY
Squamous
cell
(years)
carcinoma
135 c35
75 (90.4%) 20 (74%)
2 IN RELATION
TO AGE Adenocarcinoma
8 (9.6%) 7 (26%)
314
BERKOWITZ
ET
AL.
lesions. In these 2 patients, the prior cervical smears preceded the diagnosis of invasive cancer by more than 2 years. The cervical smears from 10 of the young patients with reportedly negative cervical cytology were reviewed at the Boston Hospital for Women, and the findings are outlined in Table 3. The cervical cytology from these 10 patients was initially read at nearby community hospitals and private cytology laboratories. We were unable to determine the cell collection techniques in the cervical smears of these patients. The cervical smears were not obtained in the remaining S patients with reportedly negative cervical cytology because the private cytology laboratories had discarded their slides. Our review of the reportedly negative cervical smears in these 10 young patients demonstrated missed cervical neoplasia in 5 cases and unsatisfactory technique for adequate interpretation in 2 cases. In one patient (DW), the reportedly negative cervical cytology demonstrated adenocarcinoma cells 19 months before a histologic diagnosis was made. DISCUSSION
Twenty-seven (24.5%) of the 110 patients with newly diagnosed invasive cervical cancer at the Boston Hospital for Women from January 1975 through June 1978 were 35 years of age or younger. In contrast, Kjorstad reported that only 7% of patients with cervical carcinoma at the Norwegian Radium Hospital were younger than 35 [2]. We cannot exclude the possibility that our observed increased frequency of cervical cancer in young women may be a reflection of differing patterns of referral to our institution. There may be a tendency to refer to our institution only those patients who are good surgical candidates, and this may TABLE REVIEW
OF REPORTEDLY TEN
YOUNG
PATIENTS CERVICAL
Patient JW
LB DW MH SL JD MP SM KP MH
Cellularity of cervical smear Adequate Adequate Adequate Adequate Poor Poor Very poor Adequate Adequate Very poor Adequate Poor Adequate
3
NEGATIVE
CERVICAL WITH
IN
CANCER
Staining of cervical smear
Our cytologic diagnosis
Poor Poor
Probable dysplasia Severe dysplasia possibly cis Atyp. benign Probable adenoca. Mild dysplasia Probable cis Atyp. benign Atyp. benign Atyp. benign Atyp. benign Probable cis Severe dysplasia Severe dysplasia
Adequate Adequate Poor Poor Very poor Adequate Adequate Very poor Adequate Adequate Adequate
CYTOLOGY
INVASIVE
Histology of cancer
Sq. cell Adenoca. Adenoca. Adenoca. Sq. cell Sq. cell Sq. cell Adenoca. Sq. cell Sq. cell
Time interval before diagnosis of cancer (months) 6 3 2 19 16 3 5 2 20 10 10 4 10
INVASIVE
CERVICAL
CARCINOMA
IN
YOUNG
WOMEN
315
increase the frequency of young patients. However, gynecologists must be aware that cervical cancer is a recognized and important problem in young women. This study does not support the concept that cervical cancer in young women is associated with a poor prognosis, predicated on the fact that the malignancy was confined to the cervix. Twenty-five (93%) of the 27 young patients with cervical carcinoma had Stage I disease at initial diagnosis. All young patients with Stage I cervical cancer are presently clinically free of tumor. The incidence of Stage I disease during the same time interval in patients older than 35 was only 52% in this series. The stage distribution of cervical cancer is therefore more favorable in young patients. The opportunities for cure in cervical cancer are greatly enhanced in patients who are diagnosed with early stage disease. Furthermore, only 4 young patients (16%) with Stage I cervical cancer were found to have pelvic nodal metastases at the time of radical hysterectomy. This observed frequency of pelvic nodal metastasis in Stage I disease is consistent with the published experience of the general population with Stage I disease from other institutions [9-l I]. Stage I cervical cancer in young patients therefore appears to be no more virulent or aggressive than the reported experience of the general population. Once the malignancy has spread beyond the cervix, the prognosis may in fact be worse in young women. Both young patients with Stage II-b disease developed pulmonary metastases. One patient developed pulmonary metastases while receiving pelvic radiotherapy and the other patient developed pulmonary involvement 8 months following completion of radiotherapy without local or regional recurrence. It is unusual for distant spread to occur so quickly in the pathogenesis of cervical cancer. However, no firm conclusions can be drawn from only two patients. Importantly, 15 of the young patients (55.5%) had reportedly negative cervical cytology smears within 2 years of the detection of invasive cervical cancer. These 15 young patients were diagnosed as having invasive cervical carcinoma only after they presented to their gynecologists with symptomatic cervical lesions. Fortunately, 14 of these 15 patients had malignancy confined to the cervix at the time of diagnosis. Abnormal cervical cytology precipitated the detection of an invasive cervical cancer in only 10 (37%) of the young patients. The cervical smears from 10 of the young patients with reportedly negative cervical cytology were reexamined at the Boston Hospital for Women. Our review demonstrated missed cervical neoplasia in 5 cases and unsatisfactory technique for adequate interpretation in 2 cases. In one patient (DW), the reportedly negative cervical cytology demonstrated adenocarcinoma cells 19 months before a histologic diagnosis was made. The frequency of false negative cervical smears in our young patients with invasive cervical cancer must be regarded as extremely worrisome. The early detection of cervical cancer depends to a large degree upon the accurate interpretation of cervical cytology. Cytology laboratories must be carefully monitored to maintain a satisfactory level of quality and competence. It is important to emphasize that cervical cytology is an adjunct and not a substitute for careful clinical examination. The gynecologist must not be lulled into a false sense of security by prior negative cervical cytology when a young patient presents with irregular vaginal bleeding. Cervical cancer must be recog-
316
BERKOWITZ
ET AL.
nized as a potential problem in any sexually active young female. All suspicious and symptomatic cervical lesions should be promptly biopsied regardless of prior reassuring cervical cytology. By being alert to the occurrence of cervical cancer in young women, the gynecologist can facilitate early detection and thereby improve opportunities for cure. ACKNOWLEDGMENTS We would like to acknowledge the careful review of cytology by Sandra Best, C.T. (ASCP), and Barbara Eugene, C.T. (ASCP), of the Cytology Laboratory of the Boston Hospital for Women.
REFERENCES I. Christopherson, W. M., Lundin, F. E., Mendez, W. M., ef al. Cervical cancer control-A study of morbidity and mortality trends over a twenty-one year period, Cancer 38, 1357-1366 (1976). 2. Kjorstad, K. Carcinoma of the cervix in young women, Obstet. Gyneco/. 50, 28-30 (1977). 3. Sadugor, M. G., and Palmer, J. P. Age, incidence and distribution in 4642 cases of carcinoma of the cervix, Amer. J. Obstet. Gynecol. 56, 680-687 (1948). 4. Kottmeier, H. L. Surgical and radiation treatment of invasive carcinoma of the uterine cervix, Acta Obstet. Gynecol. Stand. Suppl. 43, l-87 (1%4). 5. Lindell, A. Carcinoma of the cervix incidence and influence of age, Acra Radio/. Suppl. 92, I I-102 (1952). 6. Kyriakos, M., Kempson, R. L., and Perez, C. Carcinoma of the cervix in young women, Obstet. Gynecol. 38, 930-944 (1971). 7. Futoran, R. J., and Nolan, J. F. Stage I carcinoma of the uterine cervix in patients under 40 years of age, Amer. J. Obster. Gynecol. 125, 790-797 (1976). 8. Blomfield, Cl. W., Cherry, C. P., and Glucksmann, A. Biologic factors influencing the radiotherapeutic results in carcinoma of the cervix, Brir. J. Radio/. 38, 241-254 (1%5). 9. Morley, G. W., and Seski, J. C. Radical pelvic surgery versus radiation therapy for Stage I carcinoma of the cervix, Amer. J. Obstet. Gynecol. 126, 785-794 (1976). IO. Masterson, J. G. Radical surgery in early carcinoma of the cervix, Amer. J. Obster. Gynecol. 87, 601-605 (1963). Il. Plentl, A. A., and Friedman, E. A. Clinical significance of cervical lymphatics, in Lymphatic system of the female genitalia, W. B. Saunders, Philadelphia, pp. 85-115 (1971).
ONCOLOGY
Invasive
8,
311-316 (1979)
Cervical
Ross S. BERKOWITZ, RISA LAVIZZO-MOUREY,
Carcinoma
in Young Women
M.D.. ROBERT L. EHRMANN, M.D., M.D., AND ROBERT C. KNAPP, M.D.’
Division of Gynecologic Oncology of the Department of Obstetrics & Gynecology und the Department of Pathology, Harvard Medical School ctnd the Boston Hospital for Women, Boston, Mussachusetts Received May 8, 1979 Twenty-seven (24.5%) of the 110 newly diagnosed cases of invasive cervical cancer at the Boston Hospital for Women from January 1975 through June 1978 were 35 years of age or younger. Twenty-five of these young patients (93%) had Stage I cervical cancer and 2 had Stage II disease. Seven (26%) of these patients had cervical adenocarcinomas. All young patients with Stage I disease are presently clinically free of tumor. Fifteen of the young patients (55.5%) had reportedly negative cervical cytology smears prior to the detection of a symptomatic cervical malignancy. The cervical smears from 10 of the patients with reportedly negative cervical cytology were reexamined at the Boston Hospital for Women, and our review demonstrated missed cervical neoplasia in 5 cases and unsatisfactory technique for adequate interpretation in 2 cases. Abnormal cervical cytology precipitated the diagnosis of invasive cervical cancer in only 37% of the young patients. All suspicious and symptomatic cervical lesions in young women should be promptly biopsied regardless of prior reassuring cervical cytology.
Although cervical cancer in young women is an infrequent occurrence, it is important to more fully understand the natural history of this disease in young patients. Since the introduction of cytologic screening, the reduction of cervical cancer incidence in the United States has been most marked in young patients [I]. Invasive cervical cancer has been reported under the age of 35 in less than 10% of the population with this diagnosis [2,3]. However, during recent years, we have observed that cervical carcinoma has been frequently diagnosed and treated in our institution in patients under 35 years of age. Reports regarding the natural history of cervical cancer in young patients have led to conflicting conclusions. While some studies suggest a poor prognosis, other authors have found either no difference or even a better prognosis for these patients [2, 4-81. The frequent occurrence of cervical cancer in young women in our institution has provided us an opportunity to investigate the evolution of this disease process. We have been disturbed by the occurrence of sequential reportedly negative ’ Address reprint requests to Robert C. Knapp, M.D., Boston Hospital for Women, Department of Gynecology, 245 Pond Avenue, Brookline, Massachusetts 02146. 311 0090-825817910603 I l-06$0 1.00/O Copyright @ 1979 by Academic Press, Inc. All rights of reproduction in any form reserved.
312
BERKOWITZ
ET AL.
cervical cytology tests in some young patients prior to the detection of invasive cancer. The present study was undertaken to evaluate cervical cancer in patients under the age of 35 regarding stage distribution, histology, natural history, and methods of diagnosis. MATERIALS
AND METHODS
All 110 newly diagnosed cases of invasive cervical cancer at the Boston Hospital for Women from January 1975 through June 1978 were evaluated regarding patient age, race, parity, clinical stage, histologic diagnosis, and therapy. Pathologic specimens from cervical biopsies, hysterectomies, and pelvic lymph node dissections were reviewed by members of the Department of Pathology of the Boston Hospital for Women. The factors that precipitated the diagnosis of invasive cervical cancer were carefully examined in the patients 35 years of age or younger. All cervical cytology reports within 2 years of the diagnosis of invasive cervical cancer were fully reviewed in the young patients. When the prior cervical smears were reported as negative, the slides were requested for reexamination in the cytology laboratory of the Boston Hospital for Women. The cervical smears were reviewed by our cytologic technicians without their knowledge that these patients were diagnosed as having invasive cervical cancer. The smears were analyzed to assess the adequacy of the sample by the degree of cellularity, the fixation and staining quality, and the cytologic diagnosis. RESULTS
Twenty-seven patients (24.5%) of the 110 newly diagnosed cases of invasive cervical cancer were 35 years of age or younger. The youngest patient in the series was 22 years old. Among the 27 young patients, the average age was 29.6 years and the median age was 30 years. Only 1 of the 27 young patients had never been pregnant. The racial distribution of the young patients with cervical cancer was no different from that of the older population. Twenty-five of the 27 young patients with invasive cervical cancer were Caucasian. The distribution of the clinical stage of cervical cancer in relation to age is summarized in Table 1. While only 52% of patients over 35 years of age had Stage I cervical cancer, 93% of patients 35 years of age or younger had Stage I disease (P ~0.05). Two of the patients under 35 had Stage II cervical carcinoma and none had Stage III or IV at initial diagnosis. The relationship of cervical cancer histology to age is outlined in Table 2. Only 8 patients (9.6%) over the age of 35 had adenocarcinoma of the cervix. In contrast, 7 of the 27 patients (26%) who were 35 years of age or younger had cervical adenocarcinoma (P G 0.05). Twenty-four of the 25 young patients with Stage I cervical cancer were treated surgically and one patient was managed with primary radiotherapy. Four of the patients under 35 (16%) had metastatic carcinoma in their pelvic nodes at the time of radical hysterectomy. The sites of pelvic nodal involvement were as follows: one patient had one positive left iliac lymph node, one patient had two positive left iliac lymph nodes, one patient had one positive left obturator lymph node, and one
INVASIVE
CERVICAL
CARCINOMA
TABLE DISTRIBUTION
OF CLINICAL
(years)
Total No. of patients
>35
83
s35
27
Stage
YOUNG
313
WOMEN
1
STAGES
IN RELATION
Age
IN
OF CERVICAL
CANCER
TO AGE
I
Stage
43 (51.8%) 25 (92.6%)
II
29 (35%) 2 (7.4%)
Stage
III
Stage
9 ( 10.8%) 0
IV
2 (2.4%) 0
patient had four positive right iliac and obturator lymph nodes. The parametrial and vaginal tissues were pathologically free of carcinoma in the 24 cases with Stage I disease treated with surgery. All 25 young patients with Stage I cervical cancer are presently clinically free of disease. Three of the four young patients with pelvic nodal metastasis were treated with postoperative radiotherapy. The one patient with involved pelvic nodes, who did not receive irradiation postoperatively, developed a pelvic side wall recurrence 6 months after surgery. This patient was then treated with external beam radiotherapy and currently is free of carcinoma 24 months after her radiation therapy. The two young patients with Stage II-b disease were treated with primary radiotherapy and both subsequently developed pulmonary metastases. One of the two patients has died, while the other is currently being treated with chemotherapy. Twenty-five of the young patients had cervical cytology smears within 2 years of the diagnosis of invasive cervical cancer. Fifteen (55.5%) of the young patients had reportedly negative cervical cytology smears within 2 years of the detection of invasive malignancy. All of these 15 patients were discovered to have a clinically evident cervical lesion only after they presented to their gynecologist with irregular vaginal bleeding, postcoital bleeding, or persistent vaginal discharge. Fourteen of these 15 patients, who presented with symptomatic cervical lesions, were diagnosed as having Stage I-b cervical carcinoma, and the remaining patient had Stage II-b disease. Abnormal cervical cytology was the precipitating factor leading to the diagnosis of cervical cancer in only IO of the young patients (37%). Two young patients, who had prior uninvestigated abnormal cervical smears, presented to their gynecologists with postcoital bleeding due to ulcerative cervical TABLE CERVICAL
Age
CANCER
HISTOLOGY
Squamous
cell
(years)
carcinoma
135 c35
75 (90.4%) 20 (74%)
2 IN RELATION
TO AGE Adenocarcinoma
8 (9.6%) 7 (26%)
314
BERKOWITZ
ET
AL.
lesions. In these 2 patients, the prior cervical smears preceded the diagnosis of invasive cancer by more than 2 years. The cervical smears from 10 of the young patients with reportedly negative cervical cytology were reviewed at the Boston Hospital for Women, and the findings are outlined in Table 3. The cervical cytology from these 10 patients was initially read at nearby community hospitals and private cytology laboratories. We were unable to determine the cell collection techniques in the cervical smears of these patients. The cervical smears were not obtained in the remaining S patients with reportedly negative cervical cytology because the private cytology laboratories had discarded their slides. Our review of the reportedly negative cervical smears in these 10 young patients demonstrated missed cervical neoplasia in 5 cases and unsatisfactory technique for adequate interpretation in 2 cases. In one patient (DW), the reportedly negative cervical cytology demonstrated adenocarcinoma cells 19 months before a histologic diagnosis was made. DISCUSSION
Twenty-seven (24.5%) of the 110 patients with newly diagnosed invasive cervical cancer at the Boston Hospital for Women from January 1975 through June 1978 were 35 years of age or younger. In contrast, Kjorstad reported that only 7% of patients with cervical carcinoma at the Norwegian Radium Hospital were younger than 35 [2]. We cannot exclude the possibility that our observed increased frequency of cervical cancer in young women may be a reflection of differing patterns of referral to our institution. There may be a tendency to refer to our institution only those patients who are good surgical candidates, and this may TABLE REVIEW
OF REPORTEDLY TEN
YOUNG
PATIENTS CERVICAL
Patient JW
LB DW MH SL JD MP SM KP MH
Cellularity of cervical smear Adequate Adequate Adequate Adequate Poor Poor Very poor Adequate Adequate Very poor Adequate Poor Adequate
3
NEGATIVE
CERVICAL WITH
IN
CANCER
Staining of cervical smear
Our cytologic diagnosis
Poor Poor
Probable dysplasia Severe dysplasia possibly cis Atyp. benign Probable adenoca. Mild dysplasia Probable cis Atyp. benign Atyp. benign Atyp. benign Atyp. benign Probable cis Severe dysplasia Severe dysplasia
Adequate Adequate Poor Poor Very poor Adequate Adequate Very poor Adequate Adequate Adequate
CYTOLOGY
INVASIVE
Histology of cancer
Sq. cell Adenoca. Adenoca. Adenoca. Sq. cell Sq. cell Sq. cell Adenoca. Sq. cell Sq. cell
Time interval before diagnosis of cancer (months) 6 3 2 19 16 3 5 2 20 10 10 4 10
INVASIVE
CERVICAL
CARCINOMA
IN
YOUNG
WOMEN
315
increase the frequency of young patients. However, gynecologists must be aware that cervical cancer is a recognized and important problem in young women. This study does not support the concept that cervical cancer in young women is associated with a poor prognosis, predicated on the fact that the malignancy was confined to the cervix. Twenty-five (93%) of the 27 young patients with cervical carcinoma had Stage I disease at initial diagnosis. All young patients with Stage I cervical cancer are presently clinically free of tumor. The incidence of Stage I disease during the same time interval in patients older than 35 was only 52% in this series. The stage distribution of cervical cancer is therefore more favorable in young patients. The opportunities for cure in cervical cancer are greatly enhanced in patients who are diagnosed with early stage disease. Furthermore, only 4 young patients (16%) with Stage I cervical cancer were found to have pelvic nodal metastases at the time of radical hysterectomy. This observed frequency of pelvic nodal metastasis in Stage I disease is consistent with the published experience of the general population with Stage I disease from other institutions [9-l I]. Stage I cervical cancer in young patients therefore appears to be no more virulent or aggressive than the reported experience of the general population. Once the malignancy has spread beyond the cervix, the prognosis may in fact be worse in young women. Both young patients with Stage II-b disease developed pulmonary metastases. One patient developed pulmonary metastases while receiving pelvic radiotherapy and the other patient developed pulmonary involvement 8 months following completion of radiotherapy without local or regional recurrence. It is unusual for distant spread to occur so quickly in the pathogenesis of cervical cancer. However, no firm conclusions can be drawn from only two patients. Importantly, 15 of the young patients (55.5%) had reportedly negative cervical cytology smears within 2 years of the detection of invasive cervical cancer. These 15 young patients were diagnosed as having invasive cervical carcinoma only after they presented to their gynecologists with symptomatic cervical lesions. Fortunately, 14 of these 15 patients had malignancy confined to the cervix at the time of diagnosis. Abnormal cervical cytology precipitated the detection of an invasive cervical cancer in only 10 (37%) of the young patients. The cervical smears from 10 of the young patients with reportedly negative cervical cytology were reexamined at the Boston Hospital for Women. Our review demonstrated missed cervical neoplasia in 5 cases and unsatisfactory technique for adequate interpretation in 2 cases. In one patient (DW), the reportedly negative cervical cytology demonstrated adenocarcinoma cells 19 months before a histologic diagnosis was made. The frequency of false negative cervical smears in our young patients with invasive cervical cancer must be regarded as extremely worrisome. The early detection of cervical cancer depends to a large degree upon the accurate interpretation of cervical cytology. Cytology laboratories must be carefully monitored to maintain a satisfactory level of quality and competence. It is important to emphasize that cervical cytology is an adjunct and not a substitute for careful clinical examination. The gynecologist must not be lulled into a false sense of security by prior negative cervical cytology when a young patient presents with irregular vaginal bleeding. Cervical cancer must be recog-
316
BERKOWITZ
ET AL.
nized as a potential problem in any sexually active young female. All suspicious and symptomatic cervical lesions should be promptly biopsied regardless of prior reassuring cervical cytology. By being alert to the occurrence of cervical cancer in young women, the gynecologist can facilitate early detection and thereby improve opportunities for cure. ACKNOWLEDGMENTS We would like to acknowledge the careful review of cytology by Sandra Best, C.T. (ASCP), and Barbara Eugene, C.T. (ASCP), of the Cytology Laboratory of the Boston Hospital for Women.
REFERENCES I. Christopherson, W. M., Lundin, F. E., Mendez, W. M., ef al. Cervical cancer control-A study of morbidity and mortality trends over a twenty-one year period, Cancer 38, 1357-1366 (1976). 2. Kjorstad, K. Carcinoma of the cervix in young women, Obstet. Gyneco/. 50, 28-30 (1977). 3. Sadugor, M. G., and Palmer, J. P. Age, incidence and distribution in 4642 cases of carcinoma of the cervix, Amer. J. Obstet. Gynecol. 56, 680-687 (1948). 4. Kottmeier, H. L. Surgical and radiation treatment of invasive carcinoma of the uterine cervix, Acta Obstet. Gynecol. Stand. Suppl. 43, l-87 (1%4). 5. Lindell, A. Carcinoma of the cervix incidence and influence of age, Acra Radio/. Suppl. 92, I I-102 (1952). 6. Kyriakos, M., Kempson, R. L., and Perez, C. Carcinoma of the cervix in young women, Obstet. Gynecol. 38, 930-944 (1971). 7. Futoran, R. J., and Nolan, J. F. Stage I carcinoma of the uterine cervix in patients under 40 years of age, Amer. J. Obster. Gynecol. 125, 790-797 (1976). 8. Blomfield, Cl. W., Cherry, C. P., and Glucksmann, A. Biologic factors influencing the radiotherapeutic results in carcinoma of the cervix, Brir. J. Radio/. 38, 241-254 (1%5). 9. Morley, G. W., and Seski, J. C. Radical pelvic surgery versus radiation therapy for Stage I carcinoma of the cervix, Amer. J. Obstet. Gynecol. 126, 785-794 (1976). IO. Masterson, J. G. Radical surgery in early carcinoma of the cervix, Amer. J. Obster. Gynecol. 87, 601-605 (1963). Il. Plentl, A. A., and Friedman, E. A. Clinical significance of cervical lymphatics, in Lymphatic system of the female genitalia, W. B. Saunders, Philadelphia, pp. 85-115 (1971).