RESUMO
BACKGROUND: The management of cervical intraepithelial neoplasia grade 2 is a clinical dilemma. Cervical intraepithelial neoplasia grade 3 is considered a cancer precursor and is always treated with excision. Most of the cervical intraepithelial neoplasia grade 1 cases regress spontaneously, and it is internationally mostly monitored with expectant management. Surgical treatment of cervical intraepithelial neoplasia entails increased risk of preterm birth in future pregnancies. Cervical intraepithelial neoplasia grade 2 in women aged under 25 years is quite well-studied; the regression rate is high and the cervical cancer risk is low. Cervical intraepithelial neoplasia grade 2 in women aged 25 years and above, in whom the risk of occult cancer is higher, has been less studied. OBJECTIVE: This study aimed to evaluate the natural course, over 2 years, of untreated cervical intraepithelial neoplasia grade 2 in women aged 25 to 30 years and its association with human papillomavirus 16. STUDY DESIGN: The study was conducted as a prospective longitudinal multicenter clinical study during February 2017 to June 2021 at 5 colposcopy clinics managing referrals after abnormal cervical screening in Region Västra Götaland, Sweden. The per protocol group comprised 127 women, aged 25 to 30 years, with fully visible squamocolumnar junction and histologically verified cervical intraepithelial neoplasia grade 2. The patients were followed up for 2 years with colposcopy, cytology, human papillomavirus tests, and at least 2 cervical biopsies every 6 months until progression or regression. The main outcome measures were the rates of regression of cervical intraepithelial neoplasia grade 2 at 6, 12, 18, and 24 months in cases with human papillomavirus 16 and those without human papillomavirus 16. The secondary outcomes were persistence and progression. RESULTS: In the per protocol analysis, partial or total regression during the 2-year period was found in 72% of patients (95% confidence interval, 63-79). In patients with human papillomavirus 16, the regression rate was 51% (95% confidence interval, 36-66) and the progression rate was 47% (95% confidence interval, 32-62). In the human papillomavirus-non-16 group, 83% (95% confidence interval, 73-90) regressed and 16% (95% confidence interval, 9-26) progressed. Most of the regression and progression in both the groups occurred within 15 months. The difference in regression between human papillomavirus 16 and human papillomavirus-non-16 cases was statistically significant (P value=.0001), as was the difference in progression (P=.0002). CONCLUSION: The regression rate of cervical intraepithelial neoplasia grade 2 is high, and human papillomavirus 16 is a strong determinant of the natural course. Patients aged 25 to 30 years with a fully visible squamocolumnar junction and without human papillomavirus 16 should generally be recommended active surveillance for 15 months, whereas immediate treatment should be considered in cases with human papillomavirus 16.