Clinical course of untreated cervical intraepithelial neoplasia grade 2 under active surveillance: systematic review and meta-analysis

Abstract

ObjectiveTo estimate the regression, persistence, and progression of untreated cervical intraepithelial neoplasia grade 2 (CIN2) lesions managed conservatively as well as compliance with follow-up protocols.DesignSystematic review and meta-analysis.Data sourcesMedline, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 1 January 1973 to 20 August 2016.Eligibility criteriaStudies reporting on outcomes of histologically confirmed CIN2 in non-pregnant women, managed conservatively for three or more months.Data synthesisTwo reviewers extracted data and assessed risk of bias. Random effects model was used to calculate pooled proportions for each outcome, and heterogeneity was assessed using I2 statistics.Main outcome measuresRates of regression, persistence, or progression of CIN2 and default rates at different follow-up time points (3, 6, 12, 24, 36, and 60 months).Results36 studies that included 3160 women were identified (seven randomised trials, 16 prospective cohorts, and 13 retrospective cohorts; 50% of the studies were at low risk of bias). At 24 months, the pooled rates were 50% (11 studies, 819/1470 women, 95% confidence interval 43% to 57%; I2=77%) for regression, 32% (eight studies, 334/1257 women, 23% to 42%; I2=82%) for persistence, and 18% (nine studies, 282/1445 women, 11% to 27%; I2=90%) for progression. In a subgroup analysis including 1069 women aged less than 30 years, the rates were 60% (four studies, 638/1069 women, 57% to 63%; I2=0%), 23% (two studies, 226/938 women, 20% to 26%; I2=97%), and 11% (three studies, 163/1033 women, 5% to 19%; I2=67%), respectively. The rate of non-compliance (at six to 24 months of follow-up) in prospective studies was around 10%.ConclusionsMost CIN2 lesions, particularly in young women (<30 years), regress spontaneously. Active surveillance, rather than immediate intervention, is therefore justified, especially among young women who are likely to adhere to monitoring.Systematic review registrationPROSPERO 2014: CRD42014014406.

Recent increase in incidence of cervical precancerous lesions in Norway: Nationwide study from 1992 to 2016

“…Interestingly, we observed that CIN2 was more prevalent in younger ages compared to CIN3, in screened population. This observation is in line with natural history studies, which indicated that CIN2 is more likely to regress and is, therefore, more common at younger ages . While persistent HPV infection initiates the natural history of cervical cancer, and CIN3 is considered a real precancerous lesion, diagnosis of CIN2 is poorly reproducible.…”

Prognostic factors for spontaneous regression of high-risk human papillomavirus-positive cervical intra-epithelial neoplasia grade 2

“…Nevertheless, natural history studies, in which cervical intra-epithelial neoplasia grade 2 and 3 lesions were distinguished based on conventional pathological criteria, show a much higher spontaneous regression rate for grade 2 (40–74%) than for grade 3 lesions (22–33%) 6 33. Other studies confirm the high regression rate of grade 2 lesions 34. Based on these results, guidelines now advise on observational management of cervical intra-epithelial neoplasia grade 2 in younger women, to reduce overtreatment and associated long-term obstetric complications 9.…”

The Cochrane HPV vaccine review was incomplete and ignored important evidence of bias

“…Furthermore, the relationship between CIN2 and cervical cancer is not clear-cut. Most CIN2 lesions in women below age 30 regress spontaneously; an active surveillance approach has therefore been recommended for this group 16. The Cochrane review’s 26 trials mainly included women below age 30 and used frequent cervical screening (often every six months) that did not reflect real-life practice (often every three to five years6).…”