Verification of HPV16 as a good prognostic factor for cervical adeno-adenosquamous carcinoma via an international collaborative study

Objectives: This multi-center international study (Asian Gynecologic Oncology Group [AGOG]13-001/Taiwanese Gynecologic Oncology Group [TGOG]1006) was to validate human papillomavirus (HPV)16 as an independent prognostic factor of cervical adenocarcinoma and adenosquamous carcinoma (AD/ASC). Methods: Retrospective and prospective collection of patients receiving primary treatment at AGOG and TGOG member hospitals for cervical AD/ASC were enrolled. The cases treated between 1993 and 2014 were retrospectively collected, and the prospective enrollment was started since 2014. Those endometrial origin (by immunohistochemistry and imaging studies) cannot rule out were excluded for analysis. Results: A total of 354 patients were enrolled, 287 (81.1%) of which had HPV-positive tumors. The top-3 types among HPV-positive cases was HPV 18 (50.8%), HPV16 (22.9%) and HPV45 (4.0%). A total of 322 patients were eligible for prognostic analyses. Patient with HPV16-positivity had significantly longer progression-free survival (PFS) and overall survivals (OS) than those without HPV16 (p=0.001 and 0.026, respectively). By multivariate analysis, advanced FIGO stage (HR5.7, 2.4-13.5), lymph node metastasis (HR4.6, 2.7-7.9), tumor size (>4 cm HR3.3), and HPV16-positivity (HR0.3, 0.1-0.7) were independent prognostic factors for PFS. Only the former 2 variables remained significant, while HPV16-positivity was marginally significant (p=0.064) for OS. HPV-negativity rates varied across hospitals, yet it seemed to be increasing over time (4.4% versus 12.5%, p Conclusions: This study confirmed that HPV16-positivity was a good prognostic factor for PFS, yet the increasing HPV-negative AD/ASCs seemed to be a trend that needs attention.