Cervical Human Papillomavirus-Independent Squamous Cell Carcinoma: A Clinicopathological Review and Outcomes Analysis Compared With Human Papillomavirus-Associated Squamous Cell Carcinoma

Abstract

Human papillomavirus (HPV)-independent cervical squamous cell carcinomas (HPVI SCCs) represent a poorly characterized entity. We aimed to explore the clinicopathological and survival features in the largest series of HPVI SCCs and compare them to HPV-associated (HPVA) SCCs. Eighty-nine cases of SCC previously tested negative for high-risk and low-risk HPV were collected from 22 institutions. A total of 363 HPVA SCCs were retrieved from a previously published database. Demographic and clinicopathological features, including p16 and p53 immunohistochemistry, and follow-up data were recorded. Forty-nine of 89 cases were classified as true HPVI SCC (HPV-/ p16-), whereas 40 were equivocal HPVI SCC (HPV-/p16 & thorn; or HPV-/p16 not performed) and were excluded. The median age of true HPVI SCCs was 68 (range, 36-88) years and 38 (77.6%) patients were diagnosed aged 60 years or older. Seven (14.2%) had a history of uterine prolapse. Compared with HPVA SCC, patients with HPVI SCCs were older (P < .001), had larger tumors (P < .001), were diagnosed at higher Federation of Gynecology and Obstetrics stage (P < .001), recurred more