Treatment of Cervical Dysplasia Case File

Treatment of Cervical Dysplasia Case File

Eugene C. Toy, MD, Konrad P. Harms, MD, Keith O. Reeves, MD, Cristo Papasakelariou, MD, FACOG

Case 39

A 23-year-old nulliparous woman presents to your clinic for follow-up of her abnormal Pap smear. She was previously found to have LSIL on Pap smear, with a finding of CIN 1 on cervical biopsy during her colposcopy. She was managed conservatively and a repeat Pap was performed 6 months later. This Pap also demonstrated LSIL and CIN 2 at the time of colposcopy. She denies postcoital spotting, irregular bleeding, and vaginal discharge. Her sexually transmitted disease (STD) screen was negative.

➤ What is your management plan?

➤ Would checking human papillomavirus (HPV) subtypes be helpful in her management at this point?

➤ Was performing a colposcopy with the first Pap smear demonstrating LSIL warranted?

ANSWERS TO CASE 39:

Treatment of Cervical Dysplasia

Summary: A 23-year-old G0P0 woman with persistent cervical dysplasia (CIN 2) on colposcopy after 6 months of observation.

➤ Management plan: Treatment with either excision or ablation.

➤ HPV testing: No, the majority (83%) of patients with CIN 1 lesions have high-risk subtypes of HPV and testing would add little to the management.

➤ Colposcopy for LSIL: Yes, studies have shown a 15% to 30% risk of CIN 2/3 at initial colposcopy after an LSIL Pap.

ANALYSIS

Objectives

1. Become familiar with the management of CIN 1.
2. Learn the technique of both cryotherapy and loop electrosurgical excisional procedure (LEEP).
3. Become familiar with outcomes of both cryotherapy and LEEP.
4. Understand the obstetrical implications after both a cryotherapy and LEEP.

Considerations

The patient is a 23-year-old nulliparous woman with persistent cervical dysplasia. She initially had LSIL on Pap and CIN 1 on colposcopic-directed biopsy. Given the high rate of regression from CIN 1, the patient was appropriately observed with repeat cytology at a 6-month interval. Her follow-up Pap revealed LSIL and she underwent a repeat colposcopy with CIN 2 on biopsy.

At this point, observation is no longer an option and treatment should be undertaken. Cervical dysplasia can be treated with cryotherapy or conization. Given her nulliparity, cryotherapy or a LEEP conization would be the most appropriate management options.

APPROACH TO

Treating CIN

DEFINITIONS

CERVICAL INTRAEPITHELIAL NEOPLASIA (CIN): Premalignant histologic changes found in cervical epithelium. It is graded as CIN 1 through CIN 3.

LOOP ELECTROSURGICAL EXCISIONAL PROCEDURE (LEEP): A conization of the cervix using a thin electric wire loop.

LOW-GRADE SQUAMOUS INTRAEPITHELIAL LESION (LSIL): A cytologic diagnosis which has changes consistent with CIN 1.

HIGH-GRADE SQUAMOUS INTRAEPITHELIAL LESION (HSIL): A cytologic diagnosis which has cellular changes consistent with CIN 2 and CIN 3.

CLINICAL APPROACH

Worldwide, cervical cancer remains one of the leading causes of death in women in the world. Fortunately, in developed countries where cervical cancer screening programs are in place, the incidence has decreased dramatically. Screening programs allow the practitioner the opportunity to detect and effectively treat precancerous lesions, cervical intraepithelial neoplasia, before the development of invasive cervical cancer. A survey performed by the College of American Pathologists demonstrated that cervical intraepithelial lesions are a common problem and that the rate of the abnormal cytology continues to rise (1 million women/year with CIN 1). Appropriate management of cervical intraepithelial neoplasia is important for both the prevention of invasive cervical cancer and avoidance of overtreating the lesion.

Patients found to have LSIL on Pap should be referred for colposcopy due to the fact that 15% to 30% of the time CIN 2/3 is identified histologically.1,2 When colposcopy confirms CIN 1 or less, the patient should be counseled about management options of expectant management or treatment. She should be counseled about the 13% risk of progression to CIN 2/3 at 2-year follow-up and 57% rate of spontaneous regression (91% at 36 months in women aged 13 to 23 years old).3 In a younger patient who has never been pregnant and is found to have CIN 1, expectant management is a very reasonable initial management plan. When managed expectantly, cervical cytology should be obtained every 6 months twice before returning to annual cytology. If cervical dysplasia persists on subsequent cytology, treatment with either ablation or excision is indicated. HPV subtype testing has no role in the management of CIN 1 because it is found in 83% of all CIN 1 lesions.

Treatment

In general, there are two categories of treatment for CIN: ablative and excisional procedures. Studies have shown a similar rate of CIN and HPV clearance with both excisional and ablative procedures. Ablative procedures can be performed by either cryotherapy or laser vaporization. Both procedures are well tolerated by the patient and are effective (both from a recurrence and costeffectiveness standpoint). However, ablations should not be performed in patients with endocervical dysplasia and, prior to any ablative procedure, an endocervical curettage (ECC) should be done to rule out dysplasia of the endocervix. LEEP is the most common form of excisional procedure. Cold knife and laser conization are other excisional procedures less commonly used. An advantage of excisional procedures is their ability to evaluate the specimen histology. A major limitation of ablative procedures is the lack of histology for further evaluation. It has been reported that 2% to 3% of patients thought to only have CIN 2/3 were found to have adenocarcinoma in situ (AIS) or invasive cancer on excised specimens.4 With this knowledge, many practitioners prefer excision to ablation for management of CIN 2/3.

Cryotherapy utilizes either carbon dioxide or nitrous oxide to freeze the epithelium of the cervix. It can be easily performed in the office without anesthesia (when used on cervix). Water-soluble gel is often applied to the probe to enhance contact with the cervix. A two-freeze technique is often used to achieve an ice ball extension 4 to 5 mm beyond the edge of the lesion. Freeze sessions often require 5 minutes each. An ECC should be performed prior to the ablation to rule out endocervical disease. The most common complication after cryotherapy is a profuse water vaginal discharge, although cervical stenosis has also been observed.

A LEEP procedure (see Figure 39–1) can be done as an outpatient, in the OR or in the office setting (with appropriate selected patient). A cervical block using lidocaine and epinephrine is usually sufficient for anesthesia. Depending on the size of the lesion, various size loops are available based on the size of the loop (0.5, 1, 1.5, and 2 cm). A pure cutting or blended (blend 1) current is then used to excise the specimen with 50- to 60-W cutting power. Care should be taken to cause “charring” of the margins by using the appropriate current and not performing the procedure too slowly or quickly (dragging the loop). If endocervical involvement is suspected or a high-grade lesion is present, additional tissue may be excised from the endocervical canal using a small loop (5 mm). This is commonly called a “top hat.” Using a smaller loop in just the endocervical canal is thought to conserve cervical stroma and minimize risk of adverse pregnancy outcomes in the future. When using the smaller loop, the cutting power should be reduced to 30 to 40 W. The surgical bed can then be cauterized with a roller ball. Monsel solution can be applied with a cotton-tipped applicator if bleeding persists.

Figure 39–1. LEEP with “top hat.”

Complications

Adverse pregnancy outcomes such as cervical stenosis, incompetent cervix, preterm labor, preterm premature rupture of membranes (PPROM), and low birth weight have been associated with excisional procedures, however, not with ablative procedures. An exact percentage risk has not been established. Abnormal pregnancy outcomes are thought to result from two mechanisms. First, removal of cervical connective tissue reduces mechanical support and possible shortening of the cervix. In fact, patients who had previously undergone an excisional procedure have cervical lengths similar to those of women

with previous spontaneous preterm birth. Second, removal of endocervical glands can lead to reduced mucus production and alter local immunologic defense against vaginal bacteria, increasing the risk of subclinical infection of the cervix and subsequent PPROM. Studies comparing pregnancy risks for excisional procedures are inconclusive. However, many feel that cold knife cone (CKC) excisions are likely to have an increased risk of adverse pregnancy events due to the larger volume of tissue removed. The timing of a pregnancy after an excision procedure may also be important with studies showing an increased preterm birth rate with short conization-to-pregnancy interval (< 3 months). Ablative procedures do not appear to have the same obstetrical complications as excision. Knowing this information, younger patients with mild dysplasia and future childbearing plans may be better candidates for ablative procedures rather than excisional. If an excisional procedure is required in a younger patient, a LEEP procedure would be a better option than CKC.

Comprehension Questions

39.1 HPV subtyping is helpful in the initial management of which of the following cytological diagnosis?

A. HSIL

B. LSIL

C. ASC-US

D. ASC-H

39.2 What is the best management of a LEEP specimen with CIN 3 and positive margins?

A. Repeat cytology in 6 months

B. Immediate repeat LEEP (within 72 hours)

C. Delayed repeat LEEP (6 weeks after initial LEEP)

D. Repeat colposcopy

39.3 Prior to performing an ablative procedure, what test should be done?

A. HPV subtyping

B. Cervical assays for gonorrhea/chlamydia

C. Endocervical curettage

D. Vaginal culture for bacterial vaginosis

ANSWERS

39.1 C. HPV subtyping is primarily used in the triage of ASC-US. Patients with CIN already have such a prevalence of HPV that knowing the subtype would not impact your management. Patients with ASC-US can be managed either by repeat cytology, immediate colposcopy, or HPV subtyping. If high-risk HPV subtypes are identified, the patient is referred to for colposcopic examination. If the high-risk subtype is negative, cytology should be repeated in 1 year.

39.2 A. A specimen with positive margins can be followed with repeat cytology at 6 months. Rarely would you consider repeating the excisional procedure. Incomplete removal of CIN 3 has been reported to occur in 5% to 16% of excisional procedures. It is thought that the inflammatory response from tissue healing and the cauterization of the cut surface of the conization bed help prevent persistent disease.

39.3 C. An ECC should be performed on all patients prior to an ablative procedure since tissue is not obtained for histology. Performing the ECC detects possible underlying dysplasia previously not known and that may alter management.

Clinical Pearls

See Table 1-2 for definition of level of evidence and strength of recommendation

➤ Patients with LSIL should be referred to colposcopy because of the 15% to 30% risk of CIN 2/3 (Level A).

➤ Ablative and excisional procedures have equal rates of clearance of dysplasia and HPV (Level A).

➤ HPV typing is primarily useful with ASC-US cytology (Level A).

➤ All excisional procedures are associated with an increased chance of adverse obstetrical outcomes (CKC possibly the highest) (Level B).

➤ An ECC should be obtained prior to all ablative procedures (Level C).

REFERENCES

1. Law KS, Chang TC, Hsueh S, et al. High prevalence of high grade squamous intraepithelial lesions and microinvasive carcinoma in women with a cytologic diagnosis of low grade squamous intraepithelial lesions. J Reprod Med. 2001;46:61. 

2. Lonky NM, Sadeghi M, Tsadik GW, Petitti D. The clinical significance of the poor correlation of cervical dysplasia and cervical malignancy with referral cytologic results. Am J Obstet Gynecol. 1999;181:560-566. 

3. Ostor AG. Natural history of cervical intraepithelial neoplasia: a critical review. Int J Gynecol Pathol. 1993;12:186-192. 

4. Ferenczy A, Choukroun D, Arseneau J. Loop electrosurgical excision procedure for squamous intraepithelial lesions of the cervix: advantages and potential pitfalls. Obstet Gynecol. 1996;87:332-337. 

5. American College of Obstetricians and Gynecologists. Management of Abnormal Cervical Cytology and Histology. ACOG Practice Bulletin, 66.Washington DC; 2005. 

6. Baggish MS, Karram MM. Cervical surgery: conization of cervix. In: Baggish MS, Karram MM. ed. Atlas of Pelvic Anatomy and Gynecologic Surgery. 2nd ed. Philadelphia, PA: Elsevier Saunders; 2006:497-501. 

7. Crane JM, Delaney T, Hutchens D. Transvaginal ultrasound in the prediction of preterm birth after treatment for cervical intraepithelial neoplasia. Obstet Gynecol. 2006;107:37-44. 

8. Fanning J, Padratzik J. Cold knife conization vs. LEEP. Are they the same procedure? J Reprod Med. 2002;47:33-35. 

9. Greenspan DL, Faubion M, Coonrod DV, Hart KW, Mathieson K. Compliance after loop electrosurgical excision procedure or cold knife cone biopsy. Obstet Gynecol. 2007;110:675-680. 

10. Himes KP, Simhan HN. Time from cervical conization to pregnancy and preterm birth. Obstet Gynecol. 2007;109:314-319. 

11. Jakus S, Edmonds P, Dunton C, King S. Margin status and excision of cervical intraepithelial neoplasia: a review. Obstet Gynecol. 2000;55:520-527. 

12. Jancar N, Rakar S, Poljak M, Fujs K, Kocjan BJ, Vrtacnik-Bokal E. Efficiency of three surgical procedures in eliminating high-risk human papillomavirus infection in women with precancerous cervical lesions. Eur J Gynaecol Oncol. 2006;27:239-242. 

13. Kalliali I, Nieminen P, Dyba T, Pukkala E, Anttila A. Cancer free survival after CIN treatment: comparisons of treatment methods and histology. Gynecol Oncol. 2007;105:228-233. 

14. Katz VL, Lentz GM, Lobo RA, Gershenson DM. Intraepithelial neoplasia of the lower genital tract (cervix and vulva). In: Katz VL, Lentz GM, Lobo RA, Gershenson DM. Comprehensive Gynecology. 5th ed. Philadelphia, PA: Mosby; 2007:754-755. 

15. Kyrgiou M, Koliopoulos G, Martin-Hirsch P, Arbyn M, Prendiville W, Parakevaidis E. Obstetric outcomes after conservative treatment for intraepithelial or early invasive cervical lesions: systematic review and meta-analysis. Lancet. 2006;367:489-498. 

16. Luciani S, Gonzales M, Munoz S, Jeronimo J, Robles S. Effectiveness of cryotherapy treatment for cervical intraepithelial neoplasia. Inter J Gynecol Obstet. 2008;101:172-177. 

17. Mathevet P, Chemali E, Roy M, Dargent D. Long-term outcome of a randomized study comparing the three techniques of conization: cold knife, laser, and LEEP. Eur J Obstet Gynecol. 2003;106:214-218. 

18. Persad VL, Peirotic MA, Guijon FB. Management of cervical neoplasia: a 13-year experience with cryotherapy and laser. J Low Genit Tract Dis. 2001;5:199-203. 

19. Schiffman M, Solomon D. Findings to date from the ASCUS-LSIL triage study (ALTS). Arch Pathol Lab Med. 2003;127:946-949. 

20. Stenchever M, Droegemueller W, Herbst A, Mishell D. Intraepithelial Neoplasia of the Cervix. Comprehensive Gynecology. 4th ed. St. Louis, MO: Mosby 2001:877-879. 

21. The ASCUS-LSIL Triage Study (ALTS) Group. A randomized trial on the management of low-grade squamous intraepithelial lesion cytology interpretations. Am J Obstet Gynecol. 2003;188:1393-1400. 

22. Wright TC, Massad S, Dunton CJ, Spitzer M, Wilkinson EJ, Solomon D. 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. J Low Genit Tract Dis. 2007;11:223-239.

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