Comments on: Limitations of HPV DNA Testing in Screening of Cervical Adenocarcinomas - Revista Brasileira de Ginecologia e Obstetrícia
Rev Bras Ginecol Obstet. 2019;41(5):357-359
Dear Editor,
We read with interest the article on human papillomavirus (HPV) DNA testing for cervical cancer in Brazil, authored by Zeferino et al (Brazilian Association for the Lower Genital Tract Pathology and Colposcopy (ABPTGIC, in the Portuguese acronym), as well as the subsequent letter to the editor, by Dr de Alcantara Segura, and the authors’ reply. We agree that detection of adenocarcinomas represents a significant challenge for cervical cancer screening programs. In the United States, squamous cancer rates have seen a decline since the introduction of the Pap smear and molecular testing, but adenocarcinoma rates have remained unchanged (). Moreover, Australia, which arguably has a best in class vaccination and screening program, is reporting a steady increase in adenocarcinoma rates. As Dr. de Alcantara Segura points out, cytology is an insensitive method for screening adenocarcinomas. This has also been shown to be the case in the US, where Katki et al reported that 63% of adenocarcinomas showed normal cytology results. In addition, screening for adenocarcinoma precursors by HPV is clearly less sensitive than squamous cancer precursors, as evidenced by the lack of progress in reducing the adenocarcinoma incidence since the introduction of molecular testing in the 2000s (). A review of the recently published literature has identified a number of potential causes for the apparent lack of HPV detection within cervical adenocarcinoma, including the following: (i) Historical use of the Hybrid Capture 2 (HC2) assay and an associated higher rate of HPV negative cervical adenocarcinoma cases reported ; (ii) low viral load of HPV and detection only with nested polymerase chain reaction (PCR) methods; (iii) L1 vs E6/E7 detection (HPV integration and L1 deletion) ; (iv) non-HR HPV genotypes associated with some adenocarcinomas; and (v) rare histological subtypes that either have low viral loads or are HPV-negative. There are some cervical adenocarcinoma tissues that appear to be non-HPV derived. Clear cell adenocarcinoma can arise from prenatal diethylstilbestrol exposure that are not believed to be associated with high-risk HPV infections. Likewise, gastric-type adenocarcinomas are considered to be either HPV-negative, or at least, have very low levels of HPV present.
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Dear Editor,
We read with interest the article on human papillomavirus (HPV) DNA testing for cervical cancer in Brazil, authored by Zeferino et al (Brazilian Association for the Lower Genital Tract Pathology and Colposcopy (ABPTGIC, in the Portuguese acronym), as well as the subsequent letter to the editor, by Dr de Alcantara Segura, and the authors' reply. We agree that detection of adenocarcinomas represents a significant challenge for cervical cancer screening programs. In the United States, squamous cancer rates have seen a decline since the introduction of the Pap smear and molecular testing, but adenocarcinoma rates have remained unchanged (). Moreover, Australia, which arguably has a best in class vaccination and screening program, is reporting a steady increase in adenocarcinoma rates. As Dr. de Alcantara Segura points out, cytology is an insensitive method for screening adenocarcinomas. This has also been shown to be the case in the US, where Katki et al reported that 63% of adenocarcinomas showed normal cytology results. In addition, screening for adenocarcinoma precursors by HPV is clearly less sensitive than squamous cancer precursors, as evidenced by the lack of progress in reducing the adenocarcinoma incidence since the introduction of molecular testing in the 2000s (). A review of the recently published literature has identified a number of potential causes for the apparent lack of HPV detection within cervical adenocarcinoma, including the following: (i) Historical use of the Hybrid Capture 2 (HC2) assay and an associated higher rate of HPV negative cervical adenocarcinoma cases reported ; (ii) low viral load of HPV and detection only with nested polymerase chain reaction (PCR) methods; (iii) L1 vs E6/E7 detection (HPV integration and L1 deletion) ; (iv) non-HR HPV genotypes associated with some adenocarcinomas; and (v) rare histological subtypes that either have low viral loads or are HPV-negative. There are some cervical adenocarcinoma tissues that appear to be non-HPV derived. Clear cell adenocarcinoma can arise from prenatal diethylstilbestrol exposure that are not believed to be associated with high-risk HPV infections. Likewise, gastric-type adenocarcinomas are considered to be either HPV-negative, or at least, have very low levels of HPV present.
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