Background <p>Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome patients who undergo vaginoplasty are at risk of developing HPV-related lesions throughout their life, from low risk condylomata acuminata (CA) to cancerous lesions. However, the HPV status of neovaginal lesion in this patient group were often undocumented. We reported a case of CA, with HPV type 6 and 18 positive, affecting both the neovagina and vulva in a MRKH patient who underwent vaginoplasty (12 months ago). Additionally, we explore the relationship between HPV infection and neovaginal lesions through a review of current literatures.</p> Case presentation <p>A 21-year-old MRKH patient after vaginoplasty was diagnosed with condylomata acuminata in the neovagina and vulva and was HPV 6 and 18 positive. The colposcopy biopsy of the condylomata acuminata (CA) lesions in the neovagina confirmed a CA lesion, with positive immunohistochemistry (IHC) staining for low-risk HPV (lrHPV). The vulvar lesions were removed by cryoablation with liquid nitrogen, and the neovaginal lesions were treated with carbon dioxide laser ablation. Post-treatment follow up showed complete resolution of neovaginal and vulvar CA, with complete epithelization of the neovaginal lesions.</p> Conclusions <p>MRKH patients who undergo vaginoplasty are at risk of developing HPV-related lesions throughout their life. This is the first published case of coinfection with both hrHPV and lrHPV, with lrHPV-related CA in an MRKH patient after Sheares’ vaginoplasty. Routine HPV screening, HPV vaccination, and condom use should be indicated in this population.</p>