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.

BackgroundHuman papillomavirus (HPV) infections have been linked to a subset of oral and oropharyngeal cancers. However, little is known on the natural history of oral HPV infections. We designed the prospective Finnish HPV Family Study to assess the dynamics of HPV infections in parents and their infants. This study reports HPV genotype distribution and virus persistence in oral mucosa of the mothers.Materials and MethodsTotally, 324 pregnant women were enrolled at the 3rd trimester of pregnancy and followed-up for 6 years. Oral scrapings taken with a brush were collected and HPV-genotyping was performed with nested PCR and Multimetrix® test (Progen, Heidelberg, Germany). The predictors of persistent oral HPV species 7/9 infections were analyzed using generalized estimating equation models.ResultsThe point prevalence of oral HPV varied from 15% to 24% during the 6-year follow-up. Altogether, 18 HPV genotypes were identified either as single or multiple-type oral infections. HPV16 was the most prevalent type at 9.7%–18.4%, followed by HPV18, HPV6, and multiple infections. Altogether, 74 women had persistent oral HPV infection determined as at least two consecutive samples positive with the same HPV genotype. HPV16 and HPV6 were the two most frequent types to persist (76% and 9%) for a mean of 18.6 and 20.2 months, respectively, followed by multiple infections (8%) for 18.3 months. An increased risk for persistent oral HPV infection with species 7/9 was associated with being seropositive for low-risk (LR)-HPV-types at baseline, whereas the use of oral contraceptives and a second pregnancy during follow-up were protective. Clinical oral lesions were detected in 17% of these women, one-third of whom had persistent oral HPV-infections.ConclusionHPV16 and HPV6 were the most common genotypes in oral HPV-infections and were also most likely to persist. Use of oral contraceptives and a second pregnancy protected against oral HPV persistence.

HPV16 was the most frequent persisting HPV genotype followed by multiple infections. Early initiation of smoking, practicing oral sex and older age increase the risk for persistence of species 7 and 9 HPV genotypes.