GYNECOLOGIC
ONCOLOGY
42, 48-53 (19%)
Presentation of Cervical Cancer’ R. PRETORIUS,M.D.,N. Department
of Gynecologic
Oncology
SEMRAD,M.D.,W. and Pelvic
Surgery,
Southern
WATRING, M.D., California
ANDN. FOTHERINGHAM,PH.D.
Permanente
Medical
Group,
Los Angeles,
California
92120
Received December 14, 1990
To determinehow patientswith invasivecervical cancerpresent and whether presentationaffects disease-freesurvival (DFS), a review of 81 patients treated for cervical cancer by the Division of Gynecologic Oncology and Pelvic Surgery at the Southern California PermanenteMedical Group betweenJanuary 1, 1986, and December31, 1986,was performed. Fifty-six percent of patients presentedwith abnormal vaginal bleeding, twenty-eight percentpresentedwith abnormalPapanicolaou(Pap) smears,nine percent presentedwith pain, four percent presentedwith vaginal discharge,and four percent presentedwith other symptoms.Follow-up was 24 to 41 months. Patients presentingwith abnormal Pap smearshad DFS of 96%. Those presentingwith abnormal vaginal bleedinghad DFS of 51%and thosepresentingwith pain had DFS of 29%. Presentationstrongly influencesDFS ($ = 16.8, P < 0.001). Of women presenting with abnormal Pap smears,87% were Stage I and 13% were Stage II. Of women presentingwith other than abnormalPap smears,40%wereStage I, 34%were StageII, and 26% wereStageIII or IV. Presentation with abnormalPap smearand stageare significantly related ($ = 14.8, P < 0.001). Of women presentingwith abnormalPap smears,89% had cancers0 to 2 cm, 5% had cancers2.1 to 4 cm, and 5% had cancersgreaterthan 4 cm in diameter.Of women presentingwith other than abnormalPap smears,21% had cancers 0 to 2 cm, 26% had cancers2.1 to 4 cm, and 53% had cancersgreater than 4 cm in diameter. Presentationwith abnormal Pap smearis significantly associatedwith tumor size ($ = 25.4, P < 0.001). Logistic regressionanalysis was performed utilizing stage,tumor size, and presentationas independentvariableswith disease-free survival as the dependentvariable. Once stageand tumor size had beencontrolled for, presentationwith abnormalPap smearno longerpredicted disease-free survival (P > 0.1). Abnormal Pap smearsare a common presentationof invasive cervical cancer. Presentationwith abnormal Pap smear is associatedwith early stageand small tumor size but is not an independentpredictor of disease-freesurvival. Q 1~1 Academic Press, Inc.
’ The conclusions stated in this manuscript are those of the authors. They do not represent statements or conclusions of the Southern California Permanente Medical Group. 48
0090-8258191 $1.50
Copyright D 1991 by Academic Press, Inc. All rights of reproduction in any form reserved.
INTRODUCTION
Current texts state that most women with invasive cervical cancer present with abnormal vaginal bleeding [ 1,2]. Our impression is that many recently diagnosed patients presented with abnormal Papanicolaou (Pap) smears. To determine how patients with cervical cancer present and to correlate methods of presentation with disease-free survival, a review of 81 patients treated for cervical cancer by the Division of Gynecologic Oncology and Pelvic Surgery at Southern California Permanente Medical Group (SCPMG) between January 1, 1986, and December 31, 1986, was performed. MATERIALS
AND METHODS
A list of 81 women treated for invasive cervical cancer within SCPMG between January 1, 1986, and December 31, 1986, was obtained from the Kaiser Permanente Tumor Registry and the statistics kept by the Division of Gynecologic Oncology and Pelvic Surgery. A chart review of these patients was conducted; data collected included age at diagnosis; parity; menopausal status; presentation; history of Pap smears, smoking, cyrosurgery, and conization of cervix; patient’s weight; number of visits to SCPMG in the year prior to diagnosis; number of visits to the Department of Obstetrics and Gynecology in the year prior to diagnosis; histology, size, and stage of cancer; treatment; and status at last follow-up. Date .of joining Kaiser Permanente was obtained from computerized records kept by SCPMG. All of the above information was available for 20 patients. Of the remaining 61 patients with incomplete data, 42 were living and 19 were dead. An attempt was made to speak with the 42 living patients in an effort to complete their data collection; 36 patients were contacted and 6 were unable to be reached. In situations in which there was more than one presenting sign or symptom, the presentation that was as-
PRESENTATION
VI E P n 5 E 8 8
OF CERVICAL
TABLE 2 Associationof Presentationand Disease-Free Survival with Follow-up of 24 to 41 Months
30 25
Presentation
20
Disease-free survival
Abnormal Pap smear Abnormal vaginal bleeding Pain Vaginal discharge Other
15 10
P
FIG. 1. Age distribution of 81 patients with invasive cervical cancer treated within SCPMG in 1986.
signed was that which caused the patient to see the physician who made the diagnosis of invasive cervical cancer. Stage was assigned prospectively utilizing the International Federation of Gynecology and Obstetrics (1976) classification with the exception of Stage IA, which was defined as invasive carcinoma with depth of invasion less than 3 mm without vascular space invasion. Evaluation of statistical significance of the difference in proportions was performed by x2 analysis. Logistic regression analysis was performed utilizing the BMDP statistical software package [3]. All tests of significance were two-tailed. RESULTS The median age of the 81 patients with invasive cervical cancer was 49 years, with a range of 23 to 76 years. The age distribution of cases (Fig. 1) is bimodal with peaks in the 30- to 40-year and 60- to 70-year groups. Mean parity was 2.6 with 18% of women being nulliparous. Fifty-three percent of the women in this series were postmenopausal. Seven women (9%) had cancers which were TABLE 1
Presentation of 81 Women with Invasive Cervical Carcinoma Treated in 1986 Presentation
45 18 22 5
Abnormal
23 (28%)
Pain Vaginal discharge Other
100% (3/3) 100% (3/3)
Stage IA, thirty-six (46%) were Stage IB, twenty-three (28%) were Stage II, ten (12%) were Stage III, and five (6%) were Stage IV. Women with Stage IA cervical carcinoma were treated with conization followed by hysterectomy. Women with Stage IB through IIIB cervical carcinoma were treated by radical surgery, external pelvic radiation followed by brachytherapy, or a combination of surgery and radiation therapy. Of the 5 women with Stage IV disease, 4 were treated with external radiation and 1 refused therapy. Length of follow-up was 24 to 41 months. The presentation of the 81 women with invasive cervical cancer is summarized in Table 1. Forty-five (56%) patients presented with abnormal vaginal bleeding. Of these 45 patients, 19 were postmenopausal and 26 were premenopausal. Postcoital bleeding occurred in 5 patients, 4 of whom were premenopausal. Twenty-three (28%) patients presented with abnormal Pap smears. Seven (9%) presented with pain and three (4%) presented with vaginal discharge. One patient each presented with a pelvic mass, with an asymptomatic cervical lesion, and at the time of cesarean section. The association of presentation and disease-free survival with a follow-up of 24 to 41 months is summarized in Table 2. Patients presenting with abnormal Pap smears had DFS of 96%, those presenting with abnormal vaginal bleeding had DFS of 51%) and those presenting with pain had DFS of 29%. Disease-free survival in women presenting with abnormal Pap smear (22/23) is significantly different from DFS in women presenting with either ab-
No. of patients
Abnormal vaginal bleeding Postmenopausal bleeding Irregular periods Postcoital bleeding Pap smear
96% (22123) 5 1% (23/45) 29% (217)
a One patient is alive with disease and one dead of other causes.
Age Years
Total
49
CANCER
(56%) (22%) (27%) (6%)
7 (9%) 3 (4%) 3 (4%)
81 (101%)
TABLE 3 Associationof Presentationwith Stage Stage Presentation Abnormal Pap smear Abnormal bleeding Pain Vaginal discharge Other
1 20 (87%)
15 (33%) 2 (28%) 3 (100%) 3 (100%)
II
III and IV
3 (13%)
0
18 (40%)
12 (27%)
2 (28%)
3 (44%)
0
0
0
0
50
PRETORIUS
TABLE 4 Associationof Presentationwith Tumor Size Tumor size (cm) Presentation Abnormal Pap smear Abnormal bleeding Pain Vaginal discharge Other
o-2 17 6 0 1 2
(89%) (16%) (50%) (66%)
2.1-4 1 9 1 1 0
(5%) (25%) (50%) (50%)
>4 1(5%) 21 (59%) 1 (50%) 0 1 (33%)
Unknown 4 9 5 1 0
normal vaginal bleeding or pain (25/52) (x2 = 15.5, P < 0.001). In Table 3 the association of presentation with Stage is summarized. Of 23 women presenting with abnormal Pap smears, 20 were Stage I, 3 were Stage II, and none were Stage III or IV. Of 58 women presenting with other than abnormal Pap smears, 23 were Stage I, 20 were Stage II, and 15 were Stage III or IV. The proportion of Stage I cases in women who presented with abnormal Pap smears (20/23) is significantly different from that in women who presented with other than abnormal Pap smears (23/58) (x2 = 14.8, P -=c0.001). In Table 4 the relation between presentation and tumor size is shown. Tumor size was recorded in 62 of 81 patients. Of 19 women presenting with abnormal Pap smears, 17 had tumors 0 to 2 cm, 1 had a tumor 2.1 to 4 cm, and 1 had a tumor greater than 4 cm in size. Of 43 women presenting with other than abnormal Pap smears, 9 had tumors 0 to 2 cm, 11 had tumors 2.1 to 4 cm, and 23 had tumors greater than 4 cm in size. The proportion of tumors 0 to 2 cm in women presenting with abnormal Pap smears (17/19) is significantly different from that in women presenting with other than an abnormal Pap smear (9/43) (x2 = 25.2, P 0.001). Disease-free survival is significantly affected by stage and tumor size (Table 5). Disease free survival was 100% for Stage IA, 86% for Stage IB, 57% for Stage II, 10% for Stage III, and nonexistent for Stage IV (x2 = 33, P < 0.001). Women with tumor size 0 to 2 cm had DFS of 92%, those with tumor size 2.1 to 4 cm had DFS of 50%, and those with tumor size greater than 4 cm had DFS of 42% (x2 = 15.3, P < 0.001). Logistic regression analysis was performed utilizing stage and presentation as independent variables with disease-free survival as the dependent variable. In this analysis of 81 patients, low stage was strongly associated with DFS; once stage had been controlled for, presentation was not significant (P = 0.08). A second analysis was performed utilizing stage, presentation, and tumor size as the independent variables. In this analysis of 62 patients, only tumor size was a significant predictor of dis-
ET AL.
ease-free survival; once tumor size had been controlled for, neither stage nor presentation was significant. Ten of the eighty-one women (12%) with invasive cervical cancer had prior treatment for cervical intraepithelial neoplasia (CIN). One patient was treated with cautery 16 years prior to the diagnosis of cervical cancer. Six patients were treated with cryotherapy, one was treated both with cryotherapy and conization, and two were treated with conization. The interval between cryotherapy and the diagnosis of cervical cancer was 1.1 to 8 years; in one patient the length of time was unknown. The interval between conization and the diagnosis of cervical cancer was 6 to 7 years. Seven of the ten (70%) women with a history of CIN presented with abnormal Pap smears while sixteen of seventy-one (23%) women without a history of CIN presented with abnormal Pap smears. The proportion of women with a history of CIN who presented with an abnormal Pap smear is significantly different from that of those who did not have a history of CIN (x2 = 9.9, P -c 0.002). In 66 women who were members of this health maintenance organization (HMO) for more than 1 year prior to the diagnosis of cervical cancer, the last Pap smear prior to the presentation with cervical cancer was within 2 years in 25 women (38%), within 7 years in 42 (64%), greater than 7 years in 20 (30%), and unknown in 4 (6%). In 15 women who joined the HMO within 1 year of their diagnosis, the last Pap smear prior to the presentation of cervical cancer was within 2 years in 5 (33%), within 7 years in 8 (53%), greater than 7 years in 2 (13%), and unknown in 5 (33%). The frequency of Pap smears in women who joined this HMO within 1 year of their diagnosis of cervical cancer was not significantly different from that in those women who joined the HMO prior to 1 year before their diagnosis of cervical cancer. TABLE 5 Associationof Stage and Tumor Size with Disease-Free Survival Disease-free survival Stage IA IB II III IV Tumor size (cm) o-2 2.1-4 >4 Unknown
100% 86% 57% 10% 0%
(7/7) (31/36) (13/23) (l/10) (O/5)
92% (24/26) 50% (6/12) 42% (10/24) 63% (12/19)
Note. Disease-free survival is significantly associated with stage (x’ = 33, P < 0.001) and with tumor size (x’ = 15.3, P < 0.001).
PRESENTATION
OF CERVICAL
51
CANCER
between 1922 and 1939 and found less than 9% to be TABLE 6 Chance of Seeinga Practitioner or Gynecologic Practitioner asymptomatic. Truelsen did not assign a single presenwithin the Year Prior to Diagnosisof Invasive Cervical Carcinoma tation, but found that 91% of women had abnormal vagiVisits within year prior to diagnosis Stage
Practitioner
Gynecology
No data”
I II III and IV
64% (20/33) 45% (9/20) 80% Q/10)
38% (12/33) 25% (5/20) 0% (O/10)
3 3 5
Note. The decreasing chance of seeing a gynecologic practitioner in the year prior to diagnosis seen with increasing stage is significant (x2 = 5.95, P < 0.025). y Data were unavailable for 11 women who joined the health plan within 1 year of their diagnosis.
As shown in Table 6, women with Stage I cervical cancer had a 64% chance of having seen a practitioner
and a 38% chance of having seen a gynecologic practitioner within the year prior to diagnosis. Women with Stage II cervical cancer had a 45% chance of seeing any practitioner and a 25% chance of seeing a gynecologic practitioner. Women with Stage III or IV cervical cancer had an 80% chance of seeing any practitioner; none of these women saw a gynecologic practitioner in the year prior to diagnosis. The decreased chance of seeing a gynecologic practitioner seen with increasing stage is significant (x’ = 5.95, P < 0.025). Twenty-six percent (21/81) of the patients in this series had either adenocarcinoma or adenosquamous carcinoma; the remainder (74%) had squamous carcinoma. Patients with adenocarcinoma or adenosquamous carcinoma presented with abnormal Pap smears in 33% of cases, not significantly differing from the 27% of women with squamous carcinoma who presented with abnormal smears. Twenty-nine percent (2/7) of women with a history of cryotherapy developed adenocarcinoma. This is not significantly higher than the 26% (19/74) of women without a history of cryotherapy who developed adenocarcinoma or adenosquamous carcinoma.
nal bleeding, 69% had vaginal discharge, 48% had pain, 11% had bladder symptoms, and 2% had rectal symptoms. In Pardanani’s series, women treated in a community hospital between 1952 and 1967 were reviewed. One presentation was assigned to each case and 8.5% of cases were asymptomatic. A comparison of the current series with that of Pardanani is shown in Table 7. In Table 7, postcoital bleeding has been separated from abnormal vaginal bleeding and the 1 woman with an asymptomatic cervical lesion has been included with those presenting with abnormal Pap smears. In the current series, the number of asymptomatic women is three times (30% vs 8.5%) higher while the number of women presenting with postmenopausal bleeding is lower (22% vs 46%). The difference in the proportion of women presenting with abnormal vaginal bleeding (56% vs 76%) as opposed to no symptoms (30% vs 8.5%) is significant (x” = 22.0, P
ONCOLOGY
42, 48-53 (19%)
Presentation of Cervical Cancer’ R. PRETORIUS,M.D.,N. Department
of Gynecologic
Oncology
SEMRAD,M.D.,W. and Pelvic
Surgery,
Southern
WATRING, M.D., California
ANDN. FOTHERINGHAM,PH.D.
Permanente
Medical
Group,
Los Angeles,
California
92120
Received December 14, 1990
To determinehow patientswith invasivecervical cancerpresent and whether presentationaffects disease-freesurvival (DFS), a review of 81 patients treated for cervical cancer by the Division of Gynecologic Oncology and Pelvic Surgery at the Southern California PermanenteMedical Group betweenJanuary 1, 1986, and December31, 1986,was performed. Fifty-six percent of patients presentedwith abnormal vaginal bleeding, twenty-eight percentpresentedwith abnormalPapanicolaou(Pap) smears,nine percent presentedwith pain, four percent presentedwith vaginal discharge,and four percent presentedwith other symptoms.Follow-up was 24 to 41 months. Patients presentingwith abnormal Pap smearshad DFS of 96%. Those presentingwith abnormal vaginal bleedinghad DFS of 51%and thosepresentingwith pain had DFS of 29%. Presentationstrongly influencesDFS ($ = 16.8, P < 0.001). Of women presenting with abnormal Pap smears,87% were Stage I and 13% were Stage II. Of women presentingwith other than abnormalPap smears,40%wereStage I, 34%were StageII, and 26% wereStageIII or IV. Presentation with abnormalPap smearand stageare significantly related ($ = 14.8, P < 0.001). Of women presentingwith abnormalPap smears,89% had cancers0 to 2 cm, 5% had cancers2.1 to 4 cm, and 5% had cancersgreaterthan 4 cm in diameter.Of women presentingwith other than abnormalPap smears,21% had cancers 0 to 2 cm, 26% had cancers2.1 to 4 cm, and 53% had cancersgreater than 4 cm in diameter. Presentationwith abnormal Pap smearis significantly associatedwith tumor size ($ = 25.4, P < 0.001). Logistic regressionanalysis was performed utilizing stage,tumor size, and presentationas independentvariableswith disease-free survival as the dependentvariable. Once stageand tumor size had beencontrolled for, presentationwith abnormalPap smearno longerpredicted disease-free survival (P > 0.1). Abnormal Pap smearsare a common presentationof invasive cervical cancer. Presentationwith abnormal Pap smear is associatedwith early stageand small tumor size but is not an independentpredictor of disease-freesurvival. Q 1~1 Academic Press, Inc.
’ The conclusions stated in this manuscript are those of the authors. They do not represent statements or conclusions of the Southern California Permanente Medical Group. 48
0090-8258191 $1.50
Copyright D 1991 by Academic Press, Inc. All rights of reproduction in any form reserved.
INTRODUCTION
Current texts state that most women with invasive cervical cancer present with abnormal vaginal bleeding [ 1,2]. Our impression is that many recently diagnosed patients presented with abnormal Papanicolaou (Pap) smears. To determine how patients with cervical cancer present and to correlate methods of presentation with disease-free survival, a review of 81 patients treated for cervical cancer by the Division of Gynecologic Oncology and Pelvic Surgery at Southern California Permanente Medical Group (SCPMG) between January 1, 1986, and December 31, 1986, was performed. MATERIALS
AND METHODS
A list of 81 women treated for invasive cervical cancer within SCPMG between January 1, 1986, and December 31, 1986, was obtained from the Kaiser Permanente Tumor Registry and the statistics kept by the Division of Gynecologic Oncology and Pelvic Surgery. A chart review of these patients was conducted; data collected included age at diagnosis; parity; menopausal status; presentation; history of Pap smears, smoking, cyrosurgery, and conization of cervix; patient’s weight; number of visits to SCPMG in the year prior to diagnosis; number of visits to the Department of Obstetrics and Gynecology in the year prior to diagnosis; histology, size, and stage of cancer; treatment; and status at last follow-up. Date .of joining Kaiser Permanente was obtained from computerized records kept by SCPMG. All of the above information was available for 20 patients. Of the remaining 61 patients with incomplete data, 42 were living and 19 were dead. An attempt was made to speak with the 42 living patients in an effort to complete their data collection; 36 patients were contacted and 6 were unable to be reached. In situations in which there was more than one presenting sign or symptom, the presentation that was as-
PRESENTATION
VI E P n 5 E 8 8
OF CERVICAL
TABLE 2 Associationof Presentationand Disease-Free Survival with Follow-up of 24 to 41 Months
30 25
Presentation
20
Disease-free survival
Abnormal Pap smear Abnormal vaginal bleeding Pain Vaginal discharge Other
15 10
P
FIG. 1. Age distribution of 81 patients with invasive cervical cancer treated within SCPMG in 1986.
signed was that which caused the patient to see the physician who made the diagnosis of invasive cervical cancer. Stage was assigned prospectively utilizing the International Federation of Gynecology and Obstetrics (1976) classification with the exception of Stage IA, which was defined as invasive carcinoma with depth of invasion less than 3 mm without vascular space invasion. Evaluation of statistical significance of the difference in proportions was performed by x2 analysis. Logistic regression analysis was performed utilizing the BMDP statistical software package [3]. All tests of significance were two-tailed. RESULTS The median age of the 81 patients with invasive cervical cancer was 49 years, with a range of 23 to 76 years. The age distribution of cases (Fig. 1) is bimodal with peaks in the 30- to 40-year and 60- to 70-year groups. Mean parity was 2.6 with 18% of women being nulliparous. Fifty-three percent of the women in this series were postmenopausal. Seven women (9%) had cancers which were TABLE 1
Presentation of 81 Women with Invasive Cervical Carcinoma Treated in 1986 Presentation
45 18 22 5
Abnormal
23 (28%)
Pain Vaginal discharge Other
100% (3/3) 100% (3/3)
Stage IA, thirty-six (46%) were Stage IB, twenty-three (28%) were Stage II, ten (12%) were Stage III, and five (6%) were Stage IV. Women with Stage IA cervical carcinoma were treated with conization followed by hysterectomy. Women with Stage IB through IIIB cervical carcinoma were treated by radical surgery, external pelvic radiation followed by brachytherapy, or a combination of surgery and radiation therapy. Of the 5 women with Stage IV disease, 4 were treated with external radiation and 1 refused therapy. Length of follow-up was 24 to 41 months. The presentation of the 81 women with invasive cervical cancer is summarized in Table 1. Forty-five (56%) patients presented with abnormal vaginal bleeding. Of these 45 patients, 19 were postmenopausal and 26 were premenopausal. Postcoital bleeding occurred in 5 patients, 4 of whom were premenopausal. Twenty-three (28%) patients presented with abnormal Pap smears. Seven (9%) presented with pain and three (4%) presented with vaginal discharge. One patient each presented with a pelvic mass, with an asymptomatic cervical lesion, and at the time of cesarean section. The association of presentation and disease-free survival with a follow-up of 24 to 41 months is summarized in Table 2. Patients presenting with abnormal Pap smears had DFS of 96%, those presenting with abnormal vaginal bleeding had DFS of 51%) and those presenting with pain had DFS of 29%. Disease-free survival in women presenting with abnormal Pap smear (22/23) is significantly different from DFS in women presenting with either ab-
No. of patients
Abnormal vaginal bleeding Postmenopausal bleeding Irregular periods Postcoital bleeding Pap smear
96% (22123) 5 1% (23/45) 29% (217)
a One patient is alive with disease and one dead of other causes.
Age Years
Total
49
CANCER
(56%) (22%) (27%) (6%)
7 (9%) 3 (4%) 3 (4%)
81 (101%)
TABLE 3 Associationof Presentationwith Stage Stage Presentation Abnormal Pap smear Abnormal bleeding Pain Vaginal discharge Other
1 20 (87%)
15 (33%) 2 (28%) 3 (100%) 3 (100%)
II
III and IV
3 (13%)
0
18 (40%)
12 (27%)
2 (28%)
3 (44%)
0
0
0
0
50
PRETORIUS
TABLE 4 Associationof Presentationwith Tumor Size Tumor size (cm) Presentation Abnormal Pap smear Abnormal bleeding Pain Vaginal discharge Other
o-2 17 6 0 1 2
(89%) (16%) (50%) (66%)
2.1-4 1 9 1 1 0
(5%) (25%) (50%) (50%)
>4 1(5%) 21 (59%) 1 (50%) 0 1 (33%)
Unknown 4 9 5 1 0
normal vaginal bleeding or pain (25/52) (x2 = 15.5, P < 0.001). In Table 3 the association of presentation with Stage is summarized. Of 23 women presenting with abnormal Pap smears, 20 were Stage I, 3 were Stage II, and none were Stage III or IV. Of 58 women presenting with other than abnormal Pap smears, 23 were Stage I, 20 were Stage II, and 15 were Stage III or IV. The proportion of Stage I cases in women who presented with abnormal Pap smears (20/23) is significantly different from that in women who presented with other than abnormal Pap smears (23/58) (x2 = 14.8, P -=c0.001). In Table 4 the relation between presentation and tumor size is shown. Tumor size was recorded in 62 of 81 patients. Of 19 women presenting with abnormal Pap smears, 17 had tumors 0 to 2 cm, 1 had a tumor 2.1 to 4 cm, and 1 had a tumor greater than 4 cm in size. Of 43 women presenting with other than abnormal Pap smears, 9 had tumors 0 to 2 cm, 11 had tumors 2.1 to 4 cm, and 23 had tumors greater than 4 cm in size. The proportion of tumors 0 to 2 cm in women presenting with abnormal Pap smears (17/19) is significantly different from that in women presenting with other than an abnormal Pap smear (9/43) (x2 = 25.2, P 0.001). Disease-free survival is significantly affected by stage and tumor size (Table 5). Disease free survival was 100% for Stage IA, 86% for Stage IB, 57% for Stage II, 10% for Stage III, and nonexistent for Stage IV (x2 = 33, P < 0.001). Women with tumor size 0 to 2 cm had DFS of 92%, those with tumor size 2.1 to 4 cm had DFS of 50%, and those with tumor size greater than 4 cm had DFS of 42% (x2 = 15.3, P < 0.001). Logistic regression analysis was performed utilizing stage and presentation as independent variables with disease-free survival as the dependent variable. In this analysis of 81 patients, low stage was strongly associated with DFS; once stage had been controlled for, presentation was not significant (P = 0.08). A second analysis was performed utilizing stage, presentation, and tumor size as the independent variables. In this analysis of 62 patients, only tumor size was a significant predictor of dis-
ET AL.
ease-free survival; once tumor size had been controlled for, neither stage nor presentation was significant. Ten of the eighty-one women (12%) with invasive cervical cancer had prior treatment for cervical intraepithelial neoplasia (CIN). One patient was treated with cautery 16 years prior to the diagnosis of cervical cancer. Six patients were treated with cryotherapy, one was treated both with cryotherapy and conization, and two were treated with conization. The interval between cryotherapy and the diagnosis of cervical cancer was 1.1 to 8 years; in one patient the length of time was unknown. The interval between conization and the diagnosis of cervical cancer was 6 to 7 years. Seven of the ten (70%) women with a history of CIN presented with abnormal Pap smears while sixteen of seventy-one (23%) women without a history of CIN presented with abnormal Pap smears. The proportion of women with a history of CIN who presented with an abnormal Pap smear is significantly different from that of those who did not have a history of CIN (x2 = 9.9, P -c 0.002). In 66 women who were members of this health maintenance organization (HMO) for more than 1 year prior to the diagnosis of cervical cancer, the last Pap smear prior to the presentation with cervical cancer was within 2 years in 25 women (38%), within 7 years in 42 (64%), greater than 7 years in 20 (30%), and unknown in 4 (6%). In 15 women who joined the HMO within 1 year of their diagnosis, the last Pap smear prior to the presentation of cervical cancer was within 2 years in 5 (33%), within 7 years in 8 (53%), greater than 7 years in 2 (13%), and unknown in 5 (33%). The frequency of Pap smears in women who joined this HMO within 1 year of their diagnosis of cervical cancer was not significantly different from that in those women who joined the HMO prior to 1 year before their diagnosis of cervical cancer. TABLE 5 Associationof Stage and Tumor Size with Disease-Free Survival Disease-free survival Stage IA IB II III IV Tumor size (cm) o-2 2.1-4 >4 Unknown
100% 86% 57% 10% 0%
(7/7) (31/36) (13/23) (l/10) (O/5)
92% (24/26) 50% (6/12) 42% (10/24) 63% (12/19)
Note. Disease-free survival is significantly associated with stage (x’ = 33, P < 0.001) and with tumor size (x’ = 15.3, P < 0.001).
PRESENTATION
OF CERVICAL
51
CANCER
between 1922 and 1939 and found less than 9% to be TABLE 6 Chance of Seeinga Practitioner or Gynecologic Practitioner asymptomatic. Truelsen did not assign a single presenwithin the Year Prior to Diagnosisof Invasive Cervical Carcinoma tation, but found that 91% of women had abnormal vagiVisits within year prior to diagnosis Stage
Practitioner
Gynecology
No data”
I II III and IV
64% (20/33) 45% (9/20) 80% Q/10)
38% (12/33) 25% (5/20) 0% (O/10)
3 3 5
Note. The decreasing chance of seeing a gynecologic practitioner in the year prior to diagnosis seen with increasing stage is significant (x2 = 5.95, P < 0.025). y Data were unavailable for 11 women who joined the health plan within 1 year of their diagnosis.
As shown in Table 6, women with Stage I cervical cancer had a 64% chance of having seen a practitioner
and a 38% chance of having seen a gynecologic practitioner within the year prior to diagnosis. Women with Stage II cervical cancer had a 45% chance of seeing any practitioner and a 25% chance of seeing a gynecologic practitioner. Women with Stage III or IV cervical cancer had an 80% chance of seeing any practitioner; none of these women saw a gynecologic practitioner in the year prior to diagnosis. The decreased chance of seeing a gynecologic practitioner seen with increasing stage is significant (x’ = 5.95, P < 0.025). Twenty-six percent (21/81) of the patients in this series had either adenocarcinoma or adenosquamous carcinoma; the remainder (74%) had squamous carcinoma. Patients with adenocarcinoma or adenosquamous carcinoma presented with abnormal Pap smears in 33% of cases, not significantly differing from the 27% of women with squamous carcinoma who presented with abnormal smears. Twenty-nine percent (2/7) of women with a history of cryotherapy developed adenocarcinoma. This is not significantly higher than the 26% (19/74) of women without a history of cryotherapy who developed adenocarcinoma or adenosquamous carcinoma.
nal bleeding, 69% had vaginal discharge, 48% had pain, 11% had bladder symptoms, and 2% had rectal symptoms. In Pardanani’s series, women treated in a community hospital between 1952 and 1967 were reviewed. One presentation was assigned to each case and 8.5% of cases were asymptomatic. A comparison of the current series with that of Pardanani is shown in Table 7. In Table 7, postcoital bleeding has been separated from abnormal vaginal bleeding and the 1 woman with an asymptomatic cervical lesion has been included with those presenting with abnormal Pap smears. In the current series, the number of asymptomatic women is three times (30% vs 8.5%) higher while the number of women presenting with postmenopausal bleeding is lower (22% vs 46%). The difference in the proportion of women presenting with abnormal vaginal bleeding (56% vs 76%) as opposed to no symptoms (30% vs 8.5%) is significant (x” = 22.0, P
