Case Presentations: Pre-Invasive Cervical Neoplasia Kathleen M. Schmeler, M.D. Assistant Professor Department of Gynecologic Oncology

Case #1 25 yo Smokes 1 pack of cigarettes per day Routine Pap test: high-grade squamous intraepithelial lesion (HSIL) Next step? 2

Case #1 Cervical biopsy: CIN 3 Endocervical curettage: CIN 3 4

CIN 2/3 5% of women undergoing Pap tests in the USA Typically diagnosed between age 25 and 35 years Progresses to cancer 8 to 13 years after a diagnosis of CIN 2/3 Caused by persistent infection with high-risk HPV subtypes HPV infection is necessary but not sufficient to develop CIN 2/3 6

CIN 2/3 Co-Factors HIV infection Immunosuppressive therapy (renal transplant, chemotherapy) Cigarette smoking 7

Case #1 Treatment for CIN 2/3? 8

Cervical Conization Cold knife conization (CKC) Loop electrosurgical procedure (LEEP), also known as large loop excision of the transformation zone (LLETZ) Laser conization ** Hysterectomy should not be performed as the initial treatment for CIN 2/3 10

Complications of LEEP/CKC Intraoperative or postoperative bleeding Infection Cervical stenosis Infertility Pregnancy loss/Preterm birth: - CKC = 14% preterm birth rate - LEEP = 11% preterm delivery rate 11

Prognosis Untreated CIN 3: Risk of cancer is 20% at 10 years and 31% at 30 years Treated CIN 3: Risk of cancer is 0.3% at 10 years and 0.7% at 30 years McCredie et al., Lancet Onc, 2008 12

Hysterectomy Hysterectomy should NOT be performed as initial treatment for CIN 2/3 Hysterectomy indicated if: - Positive margins for CIN 2/3 and repeat excision not technically possible - Cervix/vagina scarring limiting follow-up exam - Persistent/recurrent CIN 2/3 * Consider frozen cone before hysterectomy if positive margins 13

Case #1 What if patient were pregnant with CIN3? 14

Pregnancy Do NOT treat CIN 2/3 during pregnancy Perform excision only if cancer suspected Up to 70% regress in postpartum period Significant bleeding and risk of preterm labor if treated during pregnancy ECC should never be performed during pregnancy Repeat cytology and colposcopy 6 to 12 weeks postpartum 15

Case #2 45 yo Routine Pap test shows atypical glandular cells? Work-up? 16

Case #2 Colposcopy: negative Endocervical curettage: adenocarcinoma-in-situ Endometrial biopsy: negative Next steps? 17

Case #2 Cone biopsy: adenocarcinoma-in-situ with positive margins Next steps? 18

Case #2 Repeat cone biopsy: no residual disease Next step? 19

Case #2 Hysterectomy: no residual disease 20

Adenocarcinoma-in-Situ (AIS) Atypical glandular cells without invasion Precursor to adenocarcinoma of the cervix (25% of cervical cancers) HPV infection is required (similar to squamous lesions) 10 - 13% of patients have multi-focal disease (“skip lesions”) 50% of patients have concomitant squamous dysplasia or cancer 21

Adenocarcinoma-in-Situ (AIS) Recommend CKC over LEEP due to higher probability of negative margins and no thermal artifact Standard treatment for AIS is hysterectomy once child-bearing is complete If positive cone margins, recommend repeat cone prior to hysterectomy to reduce the possibility of missing an occult cancer and performing incorrect procedure 22

Thank You 23