Comments on: Limitations of HPV DNA Testing in Screening of Cervical Adenocarcinomas.

Abstract

Dear Editor, I read with great interest the article on HPV DNA testing for cervical cancer screening in Brazil, authored by the Brazilian Association for the Lower Genital Tract Pathology and Colposcopy (ABPTGIC, in the Portuguese acronym).1 In agreement with the authors, I have found irrefutable evidence sustaining the use of molecular detection of HPV DNA in this setting. However, every method, no matter how innovative or advanced, has limitations. The “Achilles’ heel” of HPV DNA primary screening is the detection of glandular lesions. I found that the manuscript by the ABPTGIC tangentially addressed this issue. An international cross-sectional study found that 38% of adenocarcinomas were not HPV-related.2 A recently proposed histologic classification of endocervical adenocarcinoma, known as International Endocervical Adenocarcinoma Criteria and Classification (IECC),3 uses the presence of HPVrelated disease to histologically classify cervical adenocarcinomas. Among nonhuman papillomavirus-associated adenocarcinoma (NHPVA), the authors identify the following histological types: endometrial, gastric-type, minimal deviation, serous, clear-cell and mesonephric. In our practice, we have recently been involved in the case of an asymptomatic woman,HPVDNA-negative,who showed abnormal cytologic results interpreted as high-grade lesion. The patient proved to have a cervical clear-cell adenocarcinoma. This tumor is classified by the IECC group as a NHPVA and would not be identified in the screening scenario by molecular assays based on HPV DNA. In summary, it is well recognized that HPV DNA detection delivers high sensibility, which is of great help, since cytologic-based screening is known to have low sensibility and high false-negative rates.4,5 But the limitations of this molecular detection should be recognized, such as the great proportion of NHPVAs. If molecular testing for HPV DNA is to be used as a primary screening test, one must acknowledge that non-HPV-related tumors would be missed.