Clinical Question

Is watchful waiting a reasonable alternative to invasive treatment for women 25 to 30 years of age with grade 2 cervical intraepithelial neoplasia (CIN2)?

Bottom Line

For women 25 to 30 years of age with CIN2 confirmed with biopsy and a human papillomavirus (HPV) type that is not 16, a majority of lesions regress at least partially within two years without treatment. Watchful waiting may be appropriate. For women with HPV 16, only 51% had a partial or total regression of CIN2, suggesting that immediate treatment (i.e., loop electrosurgical excision procedure) is warranted. Most progression or regression was evident at 12 months. (Level of Evidence = 1b)

Synopsis

The Swedish multicenter cohort study intended to establish the natural course of CIN2 in patients 25 to 30 years of age at the time of diagnosis. The investigators included 137 patients with a histological diagnosis of CIN2, fully visible squamocolumnar junction, transformation zone type 1 or 2, and available HPV results within three months before biopsy. The authors excluded patients who were immuno-suppressed, in cancer treatment, pregnant at the time of diagnosis, or had an HIV infection or previous treatment for CIN. The follow-up evaluation included colposcopy, cytology, HPV testing, and at least two cervical biopsies every six months for up to 24 months. The loop electrosurgical excision procedure was performed in cases with progression to CIN3+ or diagnosis of atypical glandular cells or adenocarcinoma in situ during the study period. Loop electrosurgical excision was also performed at the conclusion of the study for persistent CIN2. In cases of partial regression, patients were followed up until total regression. HPV testing identified HPV 16 and 18, as well as 12 other strains as non-HPV 16/18. Ten patients did not complete the protocol as planned, leaving 127 for the per-protocol analysis. Of these, 21% had been vaccinated for HPV, and one-half were vaccinated before they were sexually active. HPV testing found that 72 patients (56%) had non-HPV 16/18, 45 (35%) had HPV 16, four (3%) had HPV 18, and six (5%) were negative for HPV. In the overall cohort, CIN2 regressed partially or totally in 68 of 82 patients (83%) with HPV status other than HPV 16, but only in 23 of 45 patients (51%) with HPV 16, a statistically significant difference (P = .0001). Only one patient (with HPV 16) had progression to stage 1A1 cervical cancer during the study period. Only one patient with HPV 16 had been vaccinated, and the vaccination was administered after they became sexually active.