Primary anogenital squamous cell carcinoma (SCC) is a locally aggressive malignancy that requires careful consideration of surgical margins. Anogenital SCC impacts the quality of life due to tissue removal, scarring, and sexual dysfunction. Mohs micrographic surgery (MMS) offers a compelling alternative to wide local excision (WLE) due to its complete margin control and potential tissue-sparing properties. This analysis systematically reviews surgical modalities used for the management of anogenital SCC. Articles meeting eligibility criteria were identified using MEDLINE (via PubMed), Embase, Cochrane, and Scopus databases. All studies investigating surgical management of anogenital SCC with WLE (including vulvectomy) or MMS were considered. A total of 70 studies met inclusion criteria: 46 examined WLE patients, 8 utilized vulvectomy, and 24 examined MMS patients. MMS patients experienced lower local recurrence rates
regional and distant recurrence rates did not differ. The local, regional, and distant recurrence rates for WLE were 17.7%, 5.1%, and 6.0%, respectively, and 5.0%, 3.8%, and 4.3% for MMS. Local recurrence was more likely in patients treated with WLE (p <
0.0001). No differences were noted in regional recurrence (p = 0.444) and distant recurrence (p = 0.420). Study limitations include differences in tumor characteristics and follow-up durations between the groups. The WLE group had larger tumors at presentation. Overall, MMS had superior outcomes for local recurrence compared to WLE and vulvectomy, making it a reasonable option for managing anogenital SCC.