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This article aims to describe the two cases in which chemotherapy and chemoradiotherapy were effective for advanced HPV-related lacrimal sac squamous cell carcinoma and avoided the need for radical surgery. This was an interventional study of two patients with advanced lacrimal sac squamous cell carcinoma. Two patients with advanced lacrimal sac squamous cell carcinoma were treated at our University Hospital between January 2020 and February 2021. Diagnosis of HPV-related lacrimal sac carcinoma was done by p16 immunostaining and RNA in situ hybridization. Received neoadjuvant chemotherapy and chemoradiotherapy, also minimally invasive surgery to remove any residual tumor if the final response, were unfavorable. HPV-related carcinoma was decided by checking p16 and RNA status. Response was assessed by computed tomography, magnetic resonance imaging, positron emission tomography-computed tomography, and endoscopic images. Both patients had positive p16 staining also HPV RNA in situ hybridization. Received definitive chemoradiotherapy instead of radical surgery after showing a partial response to neoadjuvant chemotherapy. A complete response was achieved in one patient and the other had a partial response, leaving a small residual tumor in the nose that was successfully removed by endonasal endoscopic surgery. Cure was achieved in two patients with HPV-related lacrimal sac squamous cell carcinoma by neoadjuvant chemotherapy followed by definitive chemoradiotherapy, with only one requiring minimally invasive surgery. This is a new direction in the treatment of p16-positive lacrimal sac carcinoma, especially for advanced cases, whereby molecular biological indicators can be used to avoid highly invasive surgery and preserve quality of life without compromising prognosis.

A Novel Treatment Strategy for Advanced Lacrimal Sac Carcinomas Confirmed by p16 Immunostaining