The present invention relates to methods and compositions for treating human papilloma virus (HPV)-associated diseases using an inhibitor of CXCL12 signaling. The invention further relates to methods and compositions for treating immune checkpoint blockade resistant diseases using an inhibitor of CXCL12 signaling. The invention further relates to methods and compositions for enhancing the immune response against an HPV-associated disease using an inhibitor of CXCL12 signaling.