Objective
The purpose of this study was to review the outcome of conservatively managed cervical intraepithelial neoplasia (CIN) 2 in women <25 years old.
Study Design
This was a retrospective review that included women who were <25 years old with biopsy proven CIN2 between 2005 and 2009. Analysis was performed that compared women who had immediate treatment with women whose treatment was deferred >4 months. The primary outcome measure was spontaneous regression of CIN2. Secondary outcomes were treatment rates and loss to follow-up evaluation.
Results
Of the 452 women who were identified, 256 women (57%) received immediate treatment; 157 women (35%) met the definition for conservative management, and 39 women (9%) had unknown subsequent management. Of the 157 women who were managed conservatively, 98 women (62%) showed spontaneous regression, with a median of 8 months observation. No conservatively managed women progressed to cancer.
Conclusion
Based on the 62% regression rate in this study, routine treatment may not be necessary for all women with CIN2 who are <25 years old.
The New Zealand National Cervical Screening Programme recommends that women have 3 yearly cervical smears from the age of 20 years. In Australia, cervical screening begins at age 18 years ; in the United States, women are recommended to begin screening 3 years after becoming sexually active. In the United Kingdom, screening does not commence until 25 years.
Although the peak incidence of high-grade squamous intraepithelial lesion and cervical intraepithelial neoplasia (CIN) occurs in women under the age of 25 years, cervical cancer is rare in this age group. Furthermore, progression to cancer is generally very slow, so there is a long period in which to detect and treat abnormal precancerous cervical lesions. Thus, there is a high likelihood of the detection of cervical abnormalities in this age group, but because there is little risk of invasive malignancy, intervention may not be warranted.
There is also evidence to show that CIN2 will regress in young women. Moore et al revealed that 65% of adolescents and young women (age, ≤21 years) with biopsy-proven CIN2 showed regression to normal over an 18-month period. In view of this and the rare occurrence of malignancy in young women, the American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines suggest that the initial observation of CIN2 lesions in adolescents may be considered. Colposcopy and cytologic examination at 4- to 6-month intervals is recommended for young women who are believed to be reliable for follow-up evaluation. This conservative approach allows for potential spontaneous resolution of CIN2 and thus avoids invasive treatment that is potentially harmful. In addition to the mental and physical trauma that may occur with the procedure, in recent years it has been established that excisional cervical treatment is associated with obstetric complications.
Although conservative management often is recommended for adolescents with CIN2, there is limited literature that has examined this issue in women aged 20-25 years. Yet, because cancer is an uncommon outcome and because of the potential complications of invasive treatment, some practitioners currently offer conservative management to patients in this age group.
The purpose of this study was to review the outcome of women under 25 years old with CIN2 who have been treated conservatively and, in particular, to observe the regression rate of CIN2.
Materials and Methods
Ethics approval was received from the Multi-region Ethics Committee, Ministry of Health, Wellington. This study involved retrospective review of the colposcopy databases at Christchurch, Dunedin, and Auckland Hospital colposcopy clinics. These databases were searched for women under the age of 25 years who had received a histologic diagnosis of CIN2 before May 2009. Data were available from January 2005 in Christchurch, August 2005 in Dunedin, and August 2006 in Auckland. In Auckland, a histologic diagnosis of CIN2/3 was used in 19 cases where the pathologic report did not differentiate clearly between the 2. These patients were included in the study.
Relevant patient demographics, referral information, and initial colposcopy, smear, and biopsy findings were obtained for each patient. The dates and results of all subsequent colposcopy visits were recorded from the database. Clinical records were accessed when the data were not available from the database.
Smear and biopsy specimens were reported by pathologic services at each of the 3 colposcopy clinics, and findings were recorded according to 2001 Bethesda terminology and the CIN histologic grading system. Management was based on local practice, and treatment decisions were the responsibility of the individual colposcopist.
Patients were grouped depending on their management after the initial CIN2 diagnosis. Patients who were treated within 4 months of receiving their CIN2 diagnosis were allocated to the “immediate treatment” group. Based on ASCCP guidelines that recommend 4- to 6-month follow-up examination in adolescent women with CIN2, anyone who remained untreated at ≥4 months was allocated to the “conservative management” group. Patients with no subsequent follow-up information (had not yet been seen back since their initial visit, had been transferred/referred to other health care providers, or were lost to follow-up evaluation) were allocated to the “no further follow-up” group.
The primary outcome for patients who were managed conservatively was disease regression, persistence, or progression. Regression, persistence , and progression were defined primarily by histologic findings from biopsy or treatment specimens. In the absence of histologic, cytologic, and/or colposcopy findings were used where the most severe diagnosis that was recorded was defined as the final diagnosis. Regression was defined as a lower grade lesion than CIN2 (normal, low-grade squamous intraepithelial lesion, human papillomavirus [HPV], CIN1, atypial squamous cells of undetermined significance). Persistent disease was defined as a high-grade lesion (CIN2, CIN3, high-grade squamous intraepithelial lesion, atypical squamous cells of undetermined significance–high grade). Disease progression was defined as histologic evidence of invasive cancer. If a patient had evidence of regression but at a later follow-up examination had evidence of persistent disease or progression, the latter diagnosis was used. The number of women who were treated or lost during conservative follow-up evaluation was measured as secondary outcomes. Time to final outcome was reported in months. The outcome was described at 4- to 9-, 10- to 15-, 16- to 20-, and 21- to 24-month intervals from CIN2 diagnosis.
Statistical analysis was performed with STATA software (version 9.2; Stata Corp, College Station, TX). Demographic and clinical features were compared between patients who had conservative management and both patients who were treated immediately and who had no further follow up. Normally distributed continuous data were compared using t tests. Categoric data were compared by χ 2 tests and presented as relative risks with 95% confidence intervals or with probability values.
Results
Four hundred thirty-three women who had CIN2 and 19 women who had CIN2/3 on biopsy and were <25 years old at the time of diagnosis were identified from the databases. Referral cytologic findings are documented in Table 1 . Thirty-nine percent of the women had low-grade referral smears, and 58% of the women had high-grade referral smears.
| Management group, n | |||
|---|---|---|---|
| Variable | Conservative (n = 157; 35%) | Immediate treatment (n = 256; 57%) | No further follow up (n = 39; 9%) |
| Referral smear | |||
| Normal | 1 (0.6%) | 1 (0.4%) | 0 |
| Low-grade squamous intraepithelial lesion (human papillomavirus/CIN1) | 53 (33.8%) | 69 (27.0%) | 14 (35.0%) |
| Atypial squamous cells of undetermined significance | 16 (10.2%) | 26 (10.2%) | 0 |
| Atypical squamous cells of undetermined significance? High-grade | 26 (16.6%) | 70 (27.3%) | 7 (17.9%) |
| High-grade squamous intraepithelial lesion (CIN2/3) | 60 (38.2%) | 81 (31.6%) | 17 (43.6%) |
| Unknown | 0 | 9 (3.5%) | 1 (2.6%) |
| No smear | 1 (0.6%) | 0 | 0 |
| Total | 157 (100.0%) | 256 (100.0%) | 39 (100.0%) |
| Colposcopist opinion at first visit | |||
| Normal | 7 (4.5%) | 8 (3.1%) | 1 (2.6%) |
| Low-grade human papillomavirus | 5 (3.2%) | 10 (3.9%) | 1 (2.6%) |
| Low-grade CIN1 | 77 (49.0%) | 104 (40.6%) | 14 (35.9%) |
| High-grade CIN2/3 | 65 (41.4%) | 130 (50.8%) | 21 (53.8%) |
| Adenocarcinoma in situ | 0 | 1 (0.4%) | 0 |
| Unknown | 2 (1.3%) | 1 (0.4%) | 2 (5.1%) |
| Other | 1 (0.6%) | 2 (0.8%) | 0 |
| Total | 157 (100.0%) | 256 (100.0%) | 39 (100.0%) |
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