Fehr 2013.

Methods	Retrospective study of 411 women with high‐grade VIN or VAIN who were treated at 4 colposcopy clinics in Switzerland between 1977 and 2011 Multivariate analyses were performed and multinomial logistic regression models (stepwise backward) were used to control for potential confounders including age, immune status, focality, grade, type of treatment and smoking behaviour on discrete outcomes
Participants	Women with biopsy‐proven high‐grade VIN or VAIN. Only patients with a follow‐up of 12 months or longer after initial diagnosis were included in the analysis. Women were excluded if they had a history of either invasive vulval, vaginal, anal or cervical cancer, but not CIN. Patients with invasive cancer diagnosed within 1 year of VIN diagnosis were also excluded "in order to minimize falsely detecting preexisting invasive disease due to incorrect initial diagnosis." Age: mean 46 years (SD 14, range: 17 to 90) VIN grade: mostly high‐grade VIN (n = 381; 93%) but also vaginal intraepithelial neoplasia (n = 30; 7%) Smoking: n = 173 (42%) were smokers HPV status: not documented Immunocompetence: n = 29 immunosuppressed Recurrent disease: not reported Focality: n = 103 (25%) multifocal, n = 308 unifocal (75%) Variables were not reported separately for treatment groups
Interventions	Group 1: CO2 laser vaporisation (n = 270) Group 2: surgical excision (n = 114) Group 3: vulvectomy (n = 19) Group 4: other treatments including PDT and imiquimod All positive margins were re‐excised "Follow‐up visits were usually scheduled every six months for the first five years and then on an annual basis." Mean follow‐up time was 85 months (SD 56 months; range 13 to 389 months)
Outcomes	Biopsy‐proven recurrence (≥ 12 months); progression to vulval cancer
Notes	The purpose of this study was to examine risk factors for recurrence and progression. Only patients with a follow‐up of 12 months or longer after initial diagnosis were included in the analysis. "If a patient had both excision and biopsy combined with laser evaporation during the first year, laser evaporation was considered the initial treatment since it is the more comprehensive type of therapy." We assessed risk of bias for the adjusted findings for the outcomes 'recurrence' and 'progression' There was a relatively low rate of multifocality (25%) in this study
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not a RCT
Allocation concealment (selection bias)	Unclear risk	See other bias
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	See other bias
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	See other bias
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	See other bias
Selective reporting (reporting bias)	Unclear risk	See other bias
Other bias	High risk	We had risk of bias concerns about the measurement of interventions and outcomes. Patients who received both LV and excision in the first year were analysed in the LV group and the number of women who received both treatments was not reported. Women in the LV group may therefore have had more extensive treatment during the course of the first year and this group may not be comparable to the excision only group. Early recurrences and progressions occurring in the first year were not counted but rather considered to have had inappropriate or insufficient initial treatment requiring immediate retreatment. We also had concerns about selective reporting bias with possible multiple intervention outcome testing to produce the ORs for recurrence and progressions. The number of women included in these analyses was not reported in Table 2, and the findings for excision versus LV were reported, not surgery (excision + vulvectomy) versus LV, as in Table 1.These limitations might have biased results in the direction of LV.
Overall risk	High risk	For the reasons described under 'other bias'