CERVICAL INTRAEPITHELIAL NEOPLASIA AND PREGNANCY Zulfo Godinjak Sarajevo, 24.06.2013
CIN • Cervical intraepithelial neoplasia (CIN) has its highest incidence during women's reproductive years. • Papanicolaou smear and pathological data are categorized into three groups by cervical intraepithelial neoplasia classification. • The incidence of cervical cancer increases with age.
CIN • If the mitoses and immature cells are present simply in the lower third of the epithelium, the lesion usually is designated as CIN1. • Involvement of the middle and upper thirds of the epithelium is diagnosed as CIN2 and CIN 3.
CIN • The incidence of cervical cancer in pregnancy is estimated to be 1-10000 pregnancies. Approximately 3% of cervical cancers are diagnosed during pregnancy. • The incidence of abnormal PAP smears has been reported to be 5%-8%. • Data on the spontaneous evolution of an intraepithelial neoplasia during pregnancy are quite diverse. (Frega A et al.Anticancer Res 2007;27(4C):2743-6)
CIN • 10%-70% dysplasia cases diagnosed during pregnancy regresess, and sometimes even disappear postpartum, while persistence in the severity of cervical neoplasia is reported in 25%-47% and progression occurs in 3%-30%. • However, adequate follow-up and definitive management in the postpartum period is important. (Frega A.et al.Anticancer Res 2007;27(4C):2743-6)
CIN • Cervical cancer screening is an essential component of prenatal care. • The diagnosis and management of CIN during pregnancy are challenging and sufficient information does not exist to allow for a definitive evidence - based approach. • Many techniques are traditionally recommended in the evaluation of abnormal cervical cytology and the treatment of CIN.
CIN • Colposcopy during pregnancy is difficult. The cervix becomes larger, the vaginal side walls tend to obstruct the view of the cervix. • The blood supply to the cervix is increased, and decidual changes in the epithelium can be confused with CIN. • Nonetheless, colposcopy plays a key role in a pregnant woman with an abnormal PAP test result.
CIN • If there is no evidence of invasion, further evaluation can be postponed until 6-12 weeks after delivery. • Biopsy during pregnancy can be performed safely. • However, the examiner must be ready to respond with prolonged local pressure and, on rare occasions, with suture ligation should brisk bleeding occur.
CIN • The only indication for an excisional procedure in pregnancy is the possible presence of invasive disease. • In those cases, a conization procedure is recommended. • Now when it is known that most of early lesions disappear spontaneously, treatment is indicated only for those lesions that have demonstrated a potential for further progression.
CIN • LLETZ during pregnancy can be performed if invasive cancer cannot be excluded by colposcopy, cytology or biopsy. • The procedure has a diagnostic intention but can also be a curative therapy in pregnancy, with low intraoperative, postoperative, and peripartum complication rates. (Schaefer K et al.Int J Gynecol Obstet 2012; 118(2):141-4)
CIN • Management of women with abnormal cytology in pregnancy presents both a diagnostic and therapeutic challenge for colposcopists. • Following an initial assessment, a careful follow-up is essential. • This must include colposcopy and take into account the physiological changes of the cervix during pregnancy and the puerperium.
CIN • Colposcopic impression in pregnancy correlate with cervical biopsy results and postpartum colposcopic findings when performed by expert colposcopists. • The emphasis should be on diagnosis and confirmation of CIN or carcinoma in situ, thus excluding invasive cancer.
CIN • What is an optimal management of cervical intraepithelial neoplasia (CIN) diagnosed before pregnancy?
CIN • Cold knife conisation, laser ablation, laser conisation and large loop excision are conservative methods. • Studies have shown conflicting results on the outcomes of pregnancy following these therapies that might increase the risk of preterm delivery. • The percentage of preterm birth appears as 10% and in range 6-15% evaluated for women not submitted to excisional procedures. (Patrelli TS.et al.Minerva Ginec2008;60(4):295-8
CIN • Due to the trend of increasing age of first pregnancy, abnormal PAP smears including those classified as atypical glandular cells are being found more often in early pregnancy. • Once invasive cancer is excluded, conservative management of squamous intraepithelial lesions in pregnancy is considered as safe. (Slama J.et al.Cytopathology 2012;23(6):383-8
CIN • Conservative management of women with atypical glandular cells in pregnancy is safe where invasive cancer is excluded. • As histological verification of glandular pre-cancerous lesions by punch biopsy is not reliable and the postpartum regresion rate cannot be determined precisely, conisation should be performed in all cases with atypical glandular cells or adenocarcinoma in situ. (Slama J.et al.Cytopathology 2012;23(6):383-8)
CIN • The number of relapses when comparing CIN2 and CIN3 were not significant. • The data suggest that CIN2 has lower recurrence rates, so these patients require more conservative treatment if a desire of future pregnancy is expressed. (Nomelini RS.et al. Eur J Gynaecol Oncol 2012; 33(3):245-8)
CIN • There is an increased risk of spontaneous preterm delivery after excision of CIN, in particular when the cone depth exceeded 10mm. (Simoens C. et al BJOG 2012;119(10):1247-55)
CIN • Thickness and the total volume of the excised transformation zone are associated with an increased risk of preterm labour. • Excisions thicker than 1.2 cm and larger than 6 cm carry a three times greater risk for preterm labour. (Khalid S.et al.BJOG 2012; 119(6):685-91)
CIN • Conisation for CIN affects obstetrical outcome. Babies tend to be born earlier and are smaller. • It is not clear whether this is related to the procedure or to factors linked with CIN. (Van de Vijver A.et al.BJOG 2010;117(3):268-73)
CIN • Compared with cold knife conisation, loop electrosurgical excision procedure is relatively safe. • Loop electrosurgical excision procedure should be a priority in the treatment of patients with CIN who want to become pregnant. (Guo HJ.et al. Eur J Gynaecol Oncol 2013; 34(1):79-82)
CIN • Loop electrosurgical excision procedure (LEEP) in women with CIN did not significantly increase the risk of low birth weight or preterm birth in subsequent pregnancy in comparasion to their controls, except when the size of electrosurgical loop was relatively large. (Acharya G. et al. Arch Gynecol Obstet 2005; 272(2):109-12)
CIN • A high proportion of cervical dysplasia regressed postpartum. • Cervical biopsies in pregnancy may not be necessary unless invasive cancer suspected. (Fader AN. et al. Am J Obstet Gynecol 2010; 203(2):113e1-6)
CIN • The regression rates of cervical cytologic findings compared between the vaginal delivery group and Cesarean section group were considered significant. • The rate of spontaneous regression of antepartum abnormal cervical cytology was higher after vaginal delivery. (Chung SM.et al. Gynecol Obstet Invest 2011; 72(4):234-8)
CIN • There is significantly more frequent postpartum regression of biopsy – proven CIN lesion following a vaginal delivery compared to Cesarean section. (Ueda Y.et al.Reprod Sci 2009; 16(11):1034-9)
CIN • Due to the high rates of CIN 2-3 persistance during the postpartum period, it is suggested that all patients in whom CIN2-3 was diagnosed during pregnancy are biopsed and treated if necessary during the postpartum period, with at least two year folow-up control to prevent lesion recurrence. (Coppolillo EF. et al.Acta Obstet Gynecol Scand 2013; 92(3):293-7)
CIN • Women with CIN3 have higher rates of spontaneous preterm delivery and PROM than those in the general population. • Loop electrosurgical excision procedure did not alter these pregnancy complication rates. • Women should receive adequate counseling before treatment and be reassured regarding the treatment of CIN on the risk of preterm delivery. (Shanbhag S.et al. Obstet Gynecol 2009;114(4): 727-35)
CIN • The 2006 American Society for Colposcopy and Cervical Pathology Consensus guidelines state that it is acceptable to defer colposopy until 6 weeks postpartum in pregnant patients with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL) cytology. (Wetta LA. et al. J Low Genit Tract Dis 2009; 13(3):182-5)
CIN • Expectant management for CIN 2-3 diagnosed during gestation is safe. • When discovered during pregnancy, CIN1 has significantly higher tendency to spontaneous regression in comparison to non-pregnant condition. (Serati M. Et al.Acta ObstetGynecol Scand 2008; 87(12):1296-300
CIN • The management of women with CIN 1 has been modified significantly. • In the earlier guidelines, management depended on whether the colposcopic examination was satisfactory and treatment using ablative or excisional methods was acceptable for women with CIN 1. • In the new guidelines cytological follow-up is the only recommended management option.
CIN • Conservative management (follow up) of CIN1 is acceptable, but evidence on performance of follow-up tools, such as PAP smear and human papilloma virus test is still needed. (Santos AL. et al. Acta Obstet Gynecol Scand 2006;85(4):444-50)
CIN • HPV 16/18 associated relative risk is nearly 200 times higher than that of the HPV negative population and an outstanding risk persists with duration of about 30 months. • The risk is manifested in progression to high- grade CIN lesions mainly within a 2 years interval after the first detection of HPV 16/18 infection. (Hernadi Z. et al.Eur J Obstet Gynecol Reprod Biol 2006;125(1):114-19)
Material and methods • Pregnant women with CIN • 1. CIN 1= 17 • 2. CIN 2= 15 • 3. CIN 3= 12 • Vaginal delivery
Results • After vaginal delivery • CIN 1- Normal finding 9 (53%) • CIN 2- Regression 7 (46.6%) • CIN 3- Regression 3 (25 %)
CIN Why CIN regress? Due to 1. Cervical epithel desquamation, or 2. Increased local imunological reparative response after vaginal delivery.
Conclusion • Vaginal delivery should be prefered in pregnant woman diagnosed with CIN. • There is a significant regression of CIN following vaginal delivery. • Treatment of CIN in pregnancy should be conservative. • Perform colposcopy and biopsy six weeks after delivery.
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