- Email: [email protected]
Cervical Cancer in Pregnancy
' ' ' ' ' ' '
OBSTETRICS
' ' ' ' ' ' '
CERVICAL CANCER IN PREGNANCY Catherine Allaire, MD CM, 1 Dianne Miller, BSc, MD, FRCSC, 2 1Department
of Obstetrics and Gynaecology, Gynaecologic Oncologist, British Columbia Cancer Agency, Assistant Professor, University of British Columbia 2
ABSTRACT
Cervical cancer, when it occurs during pregnancy, leads to difficult management decisions. This article reviews the available information relevant to dealing with such patients. The evaluation of an abncmnal Pap. smear and the indications for cone biopsy are discussed. The literature shows that invasive cervical carcinoma in pregnancy tends to be symptomatic and is detected at earUer stages. Prognosis appears to be the same for these patients and treatment options are similar to nonpregnant women. Timing of intervention becomes the critical issue. To obtain a viable fetus, abdominal delivery by Caesarean section is the preferred approach.
RESUME
Le cancer du col de l' uterus, lorsqu' il se presente en grossesse, pose de difficiles decisions. Cet article evalue l' information disponible et pertinente au traitement de ces patientes. L' evaluation d' une cytologie anonnale et les indications pour une biopsie du col sont discutees. Les etudes demontrent que le cancer du col en grossesse tend ai!tre symptomatique et est detecte a un stade mains avance. Ces patientes semblent avoir Ia mi!me chance de survie. Le traitement est le mi!me quoique le temps choisi pour interveru'r devient un point critique. L'accouchement par cesarienne est recommende lorsqu'il y a un foetus viable.
J SOGC KEY WORDS
Cervical carcinoma, pregnancy, almormal cytology, colposcopy.
JOURNALSOGC
138
FEBRUARY1995
1995;17:138-42
' ' ' Colposcopy has become the standard for evaluating abnormal Pap. smears and its purpose in pregnancy is to rule out invasive disease. Even in pregnancy, colposcopy is safe and reliable with an accuracy of 99.5 percent and complication rate of 0.6 percent. 1 The columnar eversion that occurs in a pregnant cervix generally makes visualization of the transformation zone easier. Redundant vaginal mucosa, a friable cervix or a large zone can make the examination more difficult technically further along in the pregnancy. Endocervical curettage is contra-indicated in pregnancy but directed biopsies can be taken from the most abnormal area. Some experts recommend deferring biopsy to the second trimester. Benedet et al. suggested that biopsy could be omitted in patients who were under 30 years of age and had cytological and colposcopic features less than CIN 3, provided they were followed with repeat colposcopy. 1 Only expert colposcopists should omit directed biopsy as it generally has very little associated morbidity. 6 The indications for cone biopsy are altered by pregnancy. Persistent smears suggesting invasive carcinoma, micro-invasive disease, colposcopic suggestion of invasion not proven by biopsy, and possible adenocarcinoma are conditions which require a cone biopsy. However, if one of these situations arises in the third trimester, the conization can be delayed to the post-partum period. If the transformation zone is not fully visualized and the cytology suggests a low-grade lesion, follow-up with repeat cytology and colposcopy is sufficient. If the cytology suggests a high-grade lesion, then a repeat examination can be performed three to four weeks later when more eversion has occurred. If the examination is still unsatisfactory, then a cone biopsy is appropriate before the third trimester. Figure 1 shows a diagnostic algorithm modified from Hacker et al. 1 The rationale for these modifications regarding cone biopsy relates to its morbidity when performed during pregnancy. Haemorrhage, immediate or delayed is the primary complication and is due to the increased vascularity of the pregnant cervix. The largest series of cone biopsies in pregnancy had a transfusion rate of 9.4 percent. 7 Perinatal mortality does not appear to be higher than in unselected pregnancies. 7·8 A cone biopsy performed during pregnancy tends to be shallower and is not curative, therefore, careful post-partum follow-up is essential to exclude residual disease. The trend had been
INTRODUCTION
Cervical cancer is the most frequent gynaecological malignancy to occur during pregnancy and it can tum a time of joy and expectation into one of frustration and anguish. It is still an uncommon occurrence, thus, prospective data are unavailable. Difficult management decisions must be made based on retrospective studies and case reports. This paper reviews the information that exists on the epidemiology, diagnosis, staging, management, and prognosis of cervical carcinoma in pregnancy. EPIDEMIOLOGY
It is important to have a uniform definition of a problem to study it properly. Unfortunately, various post-partum intervals have been used in the literature for the analysis of cases of carcinoma of the cervix associated with pregnancy. Reports vary from using only antepartum cases to including those who present up to 18 months post-partum. The largest review, by Hacker et al. used 12 months as their cut-off. 1 The general incidence of cervical dysplasia occurring during pregnancy varies according to the study population's risk factors and the nature of the screening programme. However, there does not seem to be a higher frequency of human papilloma virus (HPV) or cervical intra-epithelial neoplasia ( CIN) detected in pregnant patients when compared to non-pregnant patients from the same population. 2 The incidence of invasive cervical carcinoma during pregnancy (i.e. stage IB or more) varies significantly from one study to another with figures ranging from one in 250 to one in 5,000 pregnancies. Between 0.1 and 10 percent of cervical cancer patients are pregnant at the time of diagnosis.' The histological type of carcinoma seems to follow the same distribution as the overall population. PREVENTION AND DIAGNOSIS
The most effective way of preventing cervical carcinoma has become the detection of pre-invasive disease through the evaluation of an abnormal Papanicalaou (Pap.) smear. Cervical cytology screening programmes such as the one established in British Columbia can reduce significantly the incidence of invasive cervical carcinoma.4 The antenatal visit is an ideal opportunity to screen those women who might not have been reached otherwise and to educate them about cytology screening.
JOURNAL SOGC
139
FEBRUARY 1995
' ' ' STAGING
FIGURE 1 MANAGEMENT OF ABNORMAL PAP. SMEAR DURING PREGNANCY
The FIGO staging for cervical carcinoma can be less accurate in pregnancy. Parametrial involvement is harder to detect with a gravid uterus and this can lead to underestimation of the stage. ScatColposcopy and Biopsy (No ECC) tered reports of worse prognosis in pregnancy have Satisfactory Colposcopy Unsatisfactory Colposcopy Invasive Carcinoma been attributed to understaging. Investigations commonly used in the evaluation I I High grade Low grade Appropriate therapy cytology cytology CIN Micro-invasion of invasive cervical carcinoma must be modified in Marked discrepancy I with Pap. smear pregnant patients. Ultrasound is not useful because Pap. and colposcopy :Possibfe adenocarcinoma every 6-12 weeks it cannot re-liably distinguish physiological dilation of pregnancy from ureteral obstruction. Intravenous unsatisfactory pyelography (IVP) and CT scan should be done Pap. and colposcopy every 6-12 w!>eks selectively and with limited images to minimize fetal Third Trimester First or Second Trimester 1 radiation exposure when viability is a concern. MagVaginal delivery netic resonance imaging (MRI) is as good as CT to Vaginal delivery and Cone8iopsy p<>st-partum conization or wedge biopsy detect lymph node metastasis and to date has not I. shown any adverse fetal effects. Miero-lnvaslon CIN Studies have shown that invasive cervical canI Vaginal cle!W..ry cer tends to he seen at earlier stages when diagnosed in pregnancy. 1 " This can be explained by • Reprnued -per~ion fro~the A the fact that women tend to worry more and seek .. G~~O!il~"Obstet Gyneo0119S2;59: medical advice when bleeding occurs during pregto do colposcopically directed wedge biopsies instead of nancy. The increased vascularity of the cervix during pregnancy might also make an otherwise asymptomatic complete cone biopsies in an effort to decrease the morbidity of the procedure while maintaining diagnostic lesion more troublesome and might lead too earlier accuracy. detection. It could also be explained by the fact that patients with more advanced lesions may have more difSIGNS AND SYMPTOMS ficulty in conceiving. Patients with pre-invasive or micro-invasive cervical cancer will usually be asymptomatic and will be detected by routine antenatal cytology. However, patients with invasive disease can have multiple symptoms, the most frequent one being vaginal bleeding. When bleeding occurs in early pregnancy, it tends to be attributed to other factors such as threatened abortion or ectopic pregnancy. In later pregnancy, placental causes are suspected. Particular concerns about placenta praevia might cause deferment of the speculum examination indefinitely. These confounding factors lead to delay in diagnosis; it takes on average 4.5 months of symptoms before the diagnosis is made. 1 There should be no hesitation to take a biopsy from an abnormal area or suspicious lesion on the cervix (Figure 2), as bleeding can almost always be Squamous cell carcinoma of the cervix in pregnancy at 28 controlled by pressure. Cervical hardness is unusual in weeks gestation. pregnancy and should raise suspicion. Abnormal fap. Smear
I
I
I
JOURNAL SOGC
140
FEBRUARY 1995
' ' ' glucocorticoid prophylaxis 48 hours before intervention in pregnancies ofless than 3 2 weeks gestation. 19 Zemlickis et al. have shown that fetal outcome is not affected by cervical carcinoma.9 Planned delay of therapy requires extensive counselling of the patient by the oncologist and neonatologist.
TIMING OF INTERVENTION
With pre-invasive and micro-invasive disease, an expectant approach with vaginal delivery and post-partum treatment is generally accepted (Figure 1). With invasive disease, the timing of intervention can become an agonizing issue. The principle of expedient treatment of a malignancy must be balanced against the patient's desire regarding the pregnancy. There is no conflict when the pregnancy is unwanted or near term. When a delay in treatment is considered, the factors that effect the decision are the natural history of the tumour, the patient's prognosis, and fetal viability. The natural history of a tumour can vary depending on numerous factors including volume, histology, and presence of lymphovascular invasion. The goal of treatment is to remove the tumour before lymphatic spread occurs. There are only anecdotal reports of tumour behaviour during pregnancy. Some tumours were observed to grow rapidly while others did not change over time. Hormone receptor data have shown that squamous carcinomas are not hormonally responsive and that adenocarcinomas do not have significant progesterone or estrogen receptors. 10•11 The hormonal changes of pregnancy should, therefore, not affect their growth and this has been the clinical observation. Most series show that prognosis is not affected by pregnancy when stage is accounted for. 1•9•12 ' 11 A few papers have indicated a higher incidence of tumour-positive lymph nodes in pregnant patients. 14 •15 However, the patient's chance for cure can affect decision-making. If a patient has an advanced tumour, waiting for fetal maturity will not change her prognosis significantly. In the first trimester, most authors would agree to intervene without delay. The traditional teaching has been to delay therapy only in the late third trimester. However, the threshold of fetal viability keeps being pushed back, so that delay times can be lessened. One must keep in mind the risk of fetal morbidity secondary to prematurity. Neonatal morbidity and mortality decrease sharply after 32 weeks, and even at 28 weeks, survival is 86.9 percent. 16 Delays in treatment of up to 24 weeks have been reported in patients with stage IB disease with no adverse outcomes. 17 ' 18 These factors have to be weighed in planning the exact time of delivery. Hannigan has suggested performing maturity amniocentesis starting at 31 weeks gestation and using
JOURNAL SOGC
MODE OF DELIVERY
There has been some uncertainty about the best mode of delivery for patients with invasive cervical carcinoma. Earlier reports showed improved survival in those patients who delivered vaginally, but this was likely due to selection bias toward patients with smaller tumours. Concerns have arisen regarding possible risk of tumour dissemination, bleeding, cervical laceration, and obstructed labour with vaginal delivery. There are also case reports of metastatic disease in episiotomy sites. 20' 22 Most authors recommend a classical Caesarean section for delivery of a viable infant, followed by the treatment of choice. TREATMENT
Once the decision to intervene has been made, the treatment approach is similar to non-pregnant patients with cervical cancer. For early stage disease, radical hysterectomy and pelvic lymphadenectomy are the preferred approaches. There is no significantly increased morbidity associated with this procedure in pregnancy. 21 ·24 At an early gestational age, the fetus can be left in situ, but when the uterus becomes larger, it is technically easier to perform a fundal hysterotomy and remove the fetus. If the fetus is viable, a Caesarean section is done first using a classical incision to avoid inadvertent extention into the cervix and possible tumour dissemination. Radiation therapy is the treatment of choice for advanced disease, and an effective alternative for earlier stage disease. External radiation is given first to reduce the tumour volume and possibility of embolization should surgical evacuation of the fetus be necessary. Most patients in the first trimester will have a spontaneous abortion, on average 33 days after beginning treatment. 25 A dilatation and curettage is required if abortion has not occurred by the time of brachytherapy. In the second trimester, the fetus is less sensitive to radiation and abortion can be delayed or not occur. A dilatation and evacuation or a fundal hysterotomy may be needed.
141
FEBRUARY 1995
' ' ' Pelvic node sampling can be done at the time of hysterotomy or Caesarean section. There are scattered reports of increased complications of radiotherapy when used in pregnancy, possibly due to problems with dosimetry and infection."" 4
9.
10.
CONCLUSION 11.
Cervical carcinoma occurring during pregnancy is becoming a relatively rare event as screening programmes have been successful in reducing the general incidence of this neoplasia. Evaluation of abnormal Pap. tests in pregnancy is done to rule out invasive disease, and treatment of pre-invasive and micro-invasive disease can be delayed as necessary. Any bleeding in pregnancy should be investigated with a speculum examination and biopsies taken from abnormal lesions. The timing of intervention is the crucial issue facing the patient with invasive disease and her physician. Individual factors and patient choices must be taken into account in balancing maternal risk and fetal considerations. The prognosis does not seem to be affected by pregnancy when stage is accounted for, but there is a shift to detection at earlier stages. Treatment options are similar to those available to non-pregnant patients, with Caesarean section being recommended for delivery of a viable fetus.
12. 13.
14.
15.
16.
17.
18.
REFERENCES 1.
2.
3. 4.
5.
6.
7. 8.
Hacker NF, Berek JS, Lagasse LD, Charles EH, Savage EW, Moore JG. Carcinoma of the cervix associated with pregnancy. Obstet Gynecol 1982;59:735-46. Malone JM, Sokol RJ, Ager JW. Pregnancy, human papillomavirus and cervical intraepithelial neoplasia. Eur J Gyneac Oncol1988;9:120-4. Shingleton HM, Orr JW. Cancer of the cervix. Churchill Livingstone, Edinburgh, 1983. Benedet JL, Anderson GH, Matisic JP. A comprehensive program for cervical cancer detection and management. Am J Obstet Gynecol 1992; 166:1254-9. Benedet JL, Selke PA, Nickerson KG. Colposcopic evaluation of abnormal Papanicolaou smears in pregnancy. Am J Obstet Gynecol 1987;157:932-7. Economos K, Veridiano NP, Deike I, Collado ML, Tancer ML. Abnormal cervical cytology in pregnancy: a 17-year experience. Obstet Gynecol 1993;81 :915-8. Averette HE, Nasser N, Yankow SL. Cervical conization in
19. 20.
21.
22.
23.
24.
pregnancy. Am J Obstet Gynecol1970;106:543. Hannigan EV, Whitehouse HH, Atkinson WD, Becker SV. Cone biopsy during pregnancy. Obstet Gynecol 1982;60:450.
JOURNAL SOGC
25.
14 2
Zemlickis D, Lishner M, Degendorfer P, Panzarella T, Sutcliffe SB, Koren G. Maternal and fetal outcome after invasive cervical cancer in pregnancy. J Clin Oncol 1991 ;9:1956-61. Robertson Dl, Paslawski D, Duggan MA, Stuart GCE, Nation JG. Estrogen and progesterone receptor, human papillomavirus, and DNA ploidy analysis in invasive carcinoma of the cervix in pregnancy. AJCP 1993;1 00:18-21. Twiggs LB, Potish RA, Leung BA. Cytosolic estrogen and progesterone receptors as prognostic parameters in stage IB cervical carcinoma. Gynecol Oncol1987;28:156-60. Lee RB, Neglia W, Park RC. Cervical carcinoma in pregnancy. Obstet Gynecol 1981 ;58:584-9. Hopkins MP, Morley GW. The prognosis and management of cervical cancer associated with pregnancy. Obstet Gynecol 1992;80:9-12. Baltzer J, Regenbrecht ME, Kopcke W, Zander J. Carcinoma of the cervix and pregnancy. lnt J Gynecol Obstet 1990;31 :317-23. Nisker JA, Shubat M. Stage IB cervical carcinoma and pregnancy: report of 49 cases. Am J Obstet Gynecol 1983; 145:203-6. Effer SB, Lopes LM, Whitfield MF. When does outcome justify heroic interventions? Univariate analysis of gestational age-specific neonatal mortality and morbidity. JSOGC 1992;14:39-49. Greer BE, Easterling TR, Mclennan DA, Benedetti TJ, Cain JM, Figge DC, Tamimi HK, Jackson JC. Fetal and maternal considerations in the management of stage 1-B cervical cancer during pregnancy. Gynecol Oncol 1989;34:61-5. Duggan B, Muderspach Ll, Roman LD, Curtin JP, D'Ablaing G, Morrow CP. Cervical cancer in pregnancy: reporting on planned delay in therapy. Obstet Gynecol 1993;82:598-602. Hannigan EV. Cervical cancer in pregnancy. Clin Obstet Gynecol 1990;33:837 -45. Copeland U, Saul PB, Sneige N. Cervical adenocarcinoma: tumor implantation in the episiotomy sites of two patients. Gynecol Oncol1987;28:230-5. Burgess SP, Waymont B. Implantation of a cervical carcinoma in an episiotomy site. Case report. Br J Obstet Gynaecol 1987 ;94:598-9. Gordon AN, Jensen R, Jones HW Ill. Squamous carcinoma of the cervix complicating pregnancy: recurrence in episiotomy after vaginal delivery. Obstet Gynecol 1989; 73:850-2. Monk BJ, Montz FJ. Invasive cervical cancer complicating intrauterine pregnancy: treatment with radical hysterectomy. Obstet Gynecol1992;80:199-203. Thompson JD, Caputo TA, Franklin EW Ill, Dale E. The surgical management of invasive cancer of the cervix in pregnancy. Am J Obstet Gynecol 1975;121 :853-63. Prem KA, Makowski EL, McKelvey JL. Carcinoma of the cervix associated with pregnancy. Am J Obstet Gynecol 1966;95:99-1 05.
FEBRUARY 1995
OBSTETRICS
' ' ' ' ' ' '
CERVICAL CANCER IN PREGNANCY Catherine Allaire, MD CM, 1 Dianne Miller, BSc, MD, FRCSC, 2 1Department
of Obstetrics and Gynaecology, Gynaecologic Oncologist, British Columbia Cancer Agency, Assistant Professor, University of British Columbia 2
ABSTRACT
Cervical cancer, when it occurs during pregnancy, leads to difficult management decisions. This article reviews the available information relevant to dealing with such patients. The evaluation of an abncmnal Pap. smear and the indications for cone biopsy are discussed. The literature shows that invasive cervical carcinoma in pregnancy tends to be symptomatic and is detected at earUer stages. Prognosis appears to be the same for these patients and treatment options are similar to nonpregnant women. Timing of intervention becomes the critical issue. To obtain a viable fetus, abdominal delivery by Caesarean section is the preferred approach.
RESUME
Le cancer du col de l' uterus, lorsqu' il se presente en grossesse, pose de difficiles decisions. Cet article evalue l' information disponible et pertinente au traitement de ces patientes. L' evaluation d' une cytologie anonnale et les indications pour une biopsie du col sont discutees. Les etudes demontrent que le cancer du col en grossesse tend ai!tre symptomatique et est detecte a un stade mains avance. Ces patientes semblent avoir Ia mi!me chance de survie. Le traitement est le mi!me quoique le temps choisi pour interveru'r devient un point critique. L'accouchement par cesarienne est recommende lorsqu'il y a un foetus viable.
J SOGC KEY WORDS
Cervical carcinoma, pregnancy, almormal cytology, colposcopy.
JOURNALSOGC
138
FEBRUARY1995
1995;17:138-42
' ' ' Colposcopy has become the standard for evaluating abnormal Pap. smears and its purpose in pregnancy is to rule out invasive disease. Even in pregnancy, colposcopy is safe and reliable with an accuracy of 99.5 percent and complication rate of 0.6 percent. 1 The columnar eversion that occurs in a pregnant cervix generally makes visualization of the transformation zone easier. Redundant vaginal mucosa, a friable cervix or a large zone can make the examination more difficult technically further along in the pregnancy. Endocervical curettage is contra-indicated in pregnancy but directed biopsies can be taken from the most abnormal area. Some experts recommend deferring biopsy to the second trimester. Benedet et al. suggested that biopsy could be omitted in patients who were under 30 years of age and had cytological and colposcopic features less than CIN 3, provided they were followed with repeat colposcopy. 1 Only expert colposcopists should omit directed biopsy as it generally has very little associated morbidity. 6 The indications for cone biopsy are altered by pregnancy. Persistent smears suggesting invasive carcinoma, micro-invasive disease, colposcopic suggestion of invasion not proven by biopsy, and possible adenocarcinoma are conditions which require a cone biopsy. However, if one of these situations arises in the third trimester, the conization can be delayed to the post-partum period. If the transformation zone is not fully visualized and the cytology suggests a low-grade lesion, follow-up with repeat cytology and colposcopy is sufficient. If the cytology suggests a high-grade lesion, then a repeat examination can be performed three to four weeks later when more eversion has occurred. If the examination is still unsatisfactory, then a cone biopsy is appropriate before the third trimester. Figure 1 shows a diagnostic algorithm modified from Hacker et al. 1 The rationale for these modifications regarding cone biopsy relates to its morbidity when performed during pregnancy. Haemorrhage, immediate or delayed is the primary complication and is due to the increased vascularity of the pregnant cervix. The largest series of cone biopsies in pregnancy had a transfusion rate of 9.4 percent. 7 Perinatal mortality does not appear to be higher than in unselected pregnancies. 7·8 A cone biopsy performed during pregnancy tends to be shallower and is not curative, therefore, careful post-partum follow-up is essential to exclude residual disease. The trend had been
INTRODUCTION
Cervical cancer is the most frequent gynaecological malignancy to occur during pregnancy and it can tum a time of joy and expectation into one of frustration and anguish. It is still an uncommon occurrence, thus, prospective data are unavailable. Difficult management decisions must be made based on retrospective studies and case reports. This paper reviews the information that exists on the epidemiology, diagnosis, staging, management, and prognosis of cervical carcinoma in pregnancy. EPIDEMIOLOGY
It is important to have a uniform definition of a problem to study it properly. Unfortunately, various post-partum intervals have been used in the literature for the analysis of cases of carcinoma of the cervix associated with pregnancy. Reports vary from using only antepartum cases to including those who present up to 18 months post-partum. The largest review, by Hacker et al. used 12 months as their cut-off. 1 The general incidence of cervical dysplasia occurring during pregnancy varies according to the study population's risk factors and the nature of the screening programme. However, there does not seem to be a higher frequency of human papilloma virus (HPV) or cervical intra-epithelial neoplasia ( CIN) detected in pregnant patients when compared to non-pregnant patients from the same population. 2 The incidence of invasive cervical carcinoma during pregnancy (i.e. stage IB or more) varies significantly from one study to another with figures ranging from one in 250 to one in 5,000 pregnancies. Between 0.1 and 10 percent of cervical cancer patients are pregnant at the time of diagnosis.' The histological type of carcinoma seems to follow the same distribution as the overall population. PREVENTION AND DIAGNOSIS
The most effective way of preventing cervical carcinoma has become the detection of pre-invasive disease through the evaluation of an abnormal Papanicalaou (Pap.) smear. Cervical cytology screening programmes such as the one established in British Columbia can reduce significantly the incidence of invasive cervical carcinoma.4 The antenatal visit is an ideal opportunity to screen those women who might not have been reached otherwise and to educate them about cytology screening.
JOURNAL SOGC
139
FEBRUARY 1995
' ' ' STAGING
FIGURE 1 MANAGEMENT OF ABNORMAL PAP. SMEAR DURING PREGNANCY
The FIGO staging for cervical carcinoma can be less accurate in pregnancy. Parametrial involvement is harder to detect with a gravid uterus and this can lead to underestimation of the stage. ScatColposcopy and Biopsy (No ECC) tered reports of worse prognosis in pregnancy have Satisfactory Colposcopy Unsatisfactory Colposcopy Invasive Carcinoma been attributed to understaging. Investigations commonly used in the evaluation I I High grade Low grade Appropriate therapy cytology cytology CIN Micro-invasion of invasive cervical carcinoma must be modified in Marked discrepancy I with Pap. smear pregnant patients. Ultrasound is not useful because Pap. and colposcopy :Possibfe adenocarcinoma every 6-12 weeks it cannot re-liably distinguish physiological dilation of pregnancy from ureteral obstruction. Intravenous unsatisfactory pyelography (IVP) and CT scan should be done Pap. and colposcopy every 6-12 w!>eks selectively and with limited images to minimize fetal Third Trimester First or Second Trimester 1 radiation exposure when viability is a concern. MagVaginal delivery netic resonance imaging (MRI) is as good as CT to Vaginal delivery and Cone8iopsy p<>st-partum conization or wedge biopsy detect lymph node metastasis and to date has not I. shown any adverse fetal effects. Miero-lnvaslon CIN Studies have shown that invasive cervical canI Vaginal cle!W..ry cer tends to he seen at earlier stages when diagnosed in pregnancy. 1 " This can be explained by • Reprnued -per~ion fro~the A the fact that women tend to worry more and seek .. G~~O!il~"Obstet Gyneo0119S2;59: medical advice when bleeding occurs during pregto do colposcopically directed wedge biopsies instead of nancy. The increased vascularity of the cervix during pregnancy might also make an otherwise asymptomatic complete cone biopsies in an effort to decrease the morbidity of the procedure while maintaining diagnostic lesion more troublesome and might lead too earlier accuracy. detection. It could also be explained by the fact that patients with more advanced lesions may have more difSIGNS AND SYMPTOMS ficulty in conceiving. Patients with pre-invasive or micro-invasive cervical cancer will usually be asymptomatic and will be detected by routine antenatal cytology. However, patients with invasive disease can have multiple symptoms, the most frequent one being vaginal bleeding. When bleeding occurs in early pregnancy, it tends to be attributed to other factors such as threatened abortion or ectopic pregnancy. In later pregnancy, placental causes are suspected. Particular concerns about placenta praevia might cause deferment of the speculum examination indefinitely. These confounding factors lead to delay in diagnosis; it takes on average 4.5 months of symptoms before the diagnosis is made. 1 There should be no hesitation to take a biopsy from an abnormal area or suspicious lesion on the cervix (Figure 2), as bleeding can almost always be Squamous cell carcinoma of the cervix in pregnancy at 28 controlled by pressure. Cervical hardness is unusual in weeks gestation. pregnancy and should raise suspicion. Abnormal fap. Smear
I
I
I
JOURNAL SOGC
140
FEBRUARY 1995
' ' ' glucocorticoid prophylaxis 48 hours before intervention in pregnancies ofless than 3 2 weeks gestation. 19 Zemlickis et al. have shown that fetal outcome is not affected by cervical carcinoma.9 Planned delay of therapy requires extensive counselling of the patient by the oncologist and neonatologist.
TIMING OF INTERVENTION
With pre-invasive and micro-invasive disease, an expectant approach with vaginal delivery and post-partum treatment is generally accepted (Figure 1). With invasive disease, the timing of intervention can become an agonizing issue. The principle of expedient treatment of a malignancy must be balanced against the patient's desire regarding the pregnancy. There is no conflict when the pregnancy is unwanted or near term. When a delay in treatment is considered, the factors that effect the decision are the natural history of the tumour, the patient's prognosis, and fetal viability. The natural history of a tumour can vary depending on numerous factors including volume, histology, and presence of lymphovascular invasion. The goal of treatment is to remove the tumour before lymphatic spread occurs. There are only anecdotal reports of tumour behaviour during pregnancy. Some tumours were observed to grow rapidly while others did not change over time. Hormone receptor data have shown that squamous carcinomas are not hormonally responsive and that adenocarcinomas do not have significant progesterone or estrogen receptors. 10•11 The hormonal changes of pregnancy should, therefore, not affect their growth and this has been the clinical observation. Most series show that prognosis is not affected by pregnancy when stage is accounted for. 1•9•12 ' 11 A few papers have indicated a higher incidence of tumour-positive lymph nodes in pregnant patients. 14 •15 However, the patient's chance for cure can affect decision-making. If a patient has an advanced tumour, waiting for fetal maturity will not change her prognosis significantly. In the first trimester, most authors would agree to intervene without delay. The traditional teaching has been to delay therapy only in the late third trimester. However, the threshold of fetal viability keeps being pushed back, so that delay times can be lessened. One must keep in mind the risk of fetal morbidity secondary to prematurity. Neonatal morbidity and mortality decrease sharply after 32 weeks, and even at 28 weeks, survival is 86.9 percent. 16 Delays in treatment of up to 24 weeks have been reported in patients with stage IB disease with no adverse outcomes. 17 ' 18 These factors have to be weighed in planning the exact time of delivery. Hannigan has suggested performing maturity amniocentesis starting at 31 weeks gestation and using
JOURNAL SOGC
MODE OF DELIVERY
There has been some uncertainty about the best mode of delivery for patients with invasive cervical carcinoma. Earlier reports showed improved survival in those patients who delivered vaginally, but this was likely due to selection bias toward patients with smaller tumours. Concerns have arisen regarding possible risk of tumour dissemination, bleeding, cervical laceration, and obstructed labour with vaginal delivery. There are also case reports of metastatic disease in episiotomy sites. 20' 22 Most authors recommend a classical Caesarean section for delivery of a viable infant, followed by the treatment of choice. TREATMENT
Once the decision to intervene has been made, the treatment approach is similar to non-pregnant patients with cervical cancer. For early stage disease, radical hysterectomy and pelvic lymphadenectomy are the preferred approaches. There is no significantly increased morbidity associated with this procedure in pregnancy. 21 ·24 At an early gestational age, the fetus can be left in situ, but when the uterus becomes larger, it is technically easier to perform a fundal hysterotomy and remove the fetus. If the fetus is viable, a Caesarean section is done first using a classical incision to avoid inadvertent extention into the cervix and possible tumour dissemination. Radiation therapy is the treatment of choice for advanced disease, and an effective alternative for earlier stage disease. External radiation is given first to reduce the tumour volume and possibility of embolization should surgical evacuation of the fetus be necessary. Most patients in the first trimester will have a spontaneous abortion, on average 33 days after beginning treatment. 25 A dilatation and curettage is required if abortion has not occurred by the time of brachytherapy. In the second trimester, the fetus is less sensitive to radiation and abortion can be delayed or not occur. A dilatation and evacuation or a fundal hysterotomy may be needed.
141
FEBRUARY 1995
' ' ' Pelvic node sampling can be done at the time of hysterotomy or Caesarean section. There are scattered reports of increased complications of radiotherapy when used in pregnancy, possibly due to problems with dosimetry and infection."" 4
9.
10.
CONCLUSION 11.
Cervical carcinoma occurring during pregnancy is becoming a relatively rare event as screening programmes have been successful in reducing the general incidence of this neoplasia. Evaluation of abnormal Pap. tests in pregnancy is done to rule out invasive disease, and treatment of pre-invasive and micro-invasive disease can be delayed as necessary. Any bleeding in pregnancy should be investigated with a speculum examination and biopsies taken from abnormal lesions. The timing of intervention is the crucial issue facing the patient with invasive disease and her physician. Individual factors and patient choices must be taken into account in balancing maternal risk and fetal considerations. The prognosis does not seem to be affected by pregnancy when stage is accounted for, but there is a shift to detection at earlier stages. Treatment options are similar to those available to non-pregnant patients, with Caesarean section being recommended for delivery of a viable fetus.
12. 13.
14.
15.
16.
17.
18.
REFERENCES 1.
2.
3. 4.
5.
6.
7. 8.
Hacker NF, Berek JS, Lagasse LD, Charles EH, Savage EW, Moore JG. Carcinoma of the cervix associated with pregnancy. Obstet Gynecol 1982;59:735-46. Malone JM, Sokol RJ, Ager JW. Pregnancy, human papillomavirus and cervical intraepithelial neoplasia. Eur J Gyneac Oncol1988;9:120-4. Shingleton HM, Orr JW. Cancer of the cervix. Churchill Livingstone, Edinburgh, 1983. Benedet JL, Anderson GH, Matisic JP. A comprehensive program for cervical cancer detection and management. Am J Obstet Gynecol 1992; 166:1254-9. Benedet JL, Selke PA, Nickerson KG. Colposcopic evaluation of abnormal Papanicolaou smears in pregnancy. Am J Obstet Gynecol 1987;157:932-7. Economos K, Veridiano NP, Deike I, Collado ML, Tancer ML. Abnormal cervical cytology in pregnancy: a 17-year experience. Obstet Gynecol 1993;81 :915-8. Averette HE, Nasser N, Yankow SL. Cervical conization in
19. 20.
21.
22.
23.
24.
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FEBRUARY 1995