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Abstract
Purpose: The 2020 World Health Organization classification divided endocervical adenocarcinoma (ADC) into human papillomavirus-associated (HPVA) and human papillomavirus-independent (HPVI) ADCs. This multi-institutional study aimed to investigate the clinical features and prognosis of patients with endocervical ADC based on the updated World Health Organization classification.

Methods and materials: We retrospectively reviewed the 365 patients with endocervical ADC who underwent radical hysterectomy from 7 institutions. Tumor characteristics, patterns of failure, and survival outcomes were compared between HPVA and HPVI ADCs.

Results: Two hundred seventy-five (75.3%) and 90 (24.7%) patients had HPVA and HPVI ADC diagnoses, respectively. In all cases, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 58.2% and 71.3%, respectively. HPVI ADC showed higher rates of local recurrence (25.6% vs 10.9%) and distant metastasis (33.3% vs 17.5%) than HPVA ADC. Multivariate survival analysis revealed that HPVI ADC showed significantly worse DFS (hazard ratio [HR], 1.919; 95% confidence interval [CI], 1.324-2.781; P < .001), distant metastasis-free survival (HR, 2.100; 95% CI, 1.397-3.156; P < .001), and OS (HR, 2.481; 95% CI, 1.586-3.881; P < .001) than HPVA ADC. Patients with gastric- and serous-type HPVI ADC had significantly worse OS than those with other HPVI ADCs (P = .020). Similarly, invasive stratified mucin-producing-type HPVA ADC showed significantly worse OS than other HPVA ADCs (P < .001).

Conclusions: We demonstrated that HPVI ADC exhibited inferior DFS and OS and higher rates of local and distant recurrence compared with HPVA ADC. Gastric- and serous-type HPVI ADCs and invasive stratified mucin-producing-type HPVA ADC showed worse OS than other types of HPVI and HPVA ADCs, respectively. Our observation of significant differences in prognoses according to the histologic types needs to be validated in larger cohorts of patients with endocervical ADC.

Affiliations

Won Kyung Cho 1, Hyun-Soo Kim 2, Won Park 3, Yeon-Sil Kim 4, Jun Kang 5, Yong Bae Kim 6, Young Seok Kim 7, Yeon Joo Kim 7, Kyu-Rae Kim 8, Jin Hee Kim 9, Sun Young Kwon 10, Jin Hwa Choi 11, Meesun Yoon 12, Nah Ihm Kim 13
1Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
2Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
3Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: wonro.park@samsung.com.
4Department of Radiation Oncology, Seoul St. Mary's Hospital, Catholic University of Korea, Seoul, Republic of Korea. Electronic address: yeonkim7@catholic.ac.kr.
5Department of Pathology, Seoul St. Mary's Hospital, Catholic University of Korea, Seoul, Republic of Korea.
6Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
7Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
8Department of Pathology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, Republic of Korea.
9Department of Radiation Oncology, Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Republic of Korea.
10Department of Pathology, Dongsan Hospital, Keimyung University School of Medicine, Daegu, Republic of Korea.
11Department of Radiation Oncology, Chung-Ang University Hospital, Seoul, Republic of Korea.
12Department of Radiation Oncology, Chonnam National University Medical School, Chonnam, Republic of Korea.
13Department of Pathology, Chonnam National University Hospital, Chonnam, Republic of Korea