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.

Two hundred fifty-six women (57%) were treated immediately; 157 women (35%) met the definition of conservative management for CIN2. For the remaining 39 women (9%), the management was unknown because of referral to other centers (15 women) or loss to follow-up evaluation (16 women) or because the patient had not yet been observed (8 women).

Table 2 shows the demographic characteristics by management group. The mean age was significantly different between management groups (20.9 years in the conservative management group, 21.9 years in the immediate treatment group, and 21.3 years in the no further follow-up group; P < .001). Women under the age of 20 years were 2.0 times more likely (95% confidence interval, 1.5–2.5) to be managed conservatively than women aged 20-25 years. Data on parity were unavailable for women from 1 center. Nulliparous women were more likely to be managed conservatively than multiparous women ( P = .02). Data on oral contraceptive use and sexually transmitted disease history were not available for all cases and were not analyzed.

TABLE 2

Demographic characteristics of young women with histologically proven CIN 2 by management group

	Management group, n
Variable	Conservative (n = 157; 35%)	Immediate treatment (n = 256; 57%)	No further follow up (n = 39; 9%)	Relative risk (95% CI) a	P value
Age, y
<20	31	15	6	2.0 (1.5–2.5)
20-25	126	241	33	Reference
Mean	20.9	21.9	21.3		< .001
Ethnicity
New Zealand European/European	129	192	32
Maori	9	27	2
Pacific Peoples	2	11	2
Asian	4	6	1
Other	4	11	1
Not stated/unknown	9	9	1		.5
Smoking
Yes	66	104	15	1.0 (0.8–1.3)
No	72	110	18	Reference
Not specified	19	42	6		.8
Colposcopy clinic
A	78	163	18	0.5 (0.4–0.7)
B	64	38	11	Reference
C	15	55	10	0.3 (0.2–0.5)

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