Question Does HPV negative cervical cancer ever occur?
Synopsis Although human papillomavirus (HPV) is well established as a causal agent in cervical cancer, most studies have shown a subgroup of up to 10% of cervical cancers that test negative for it. In this German prospective cohort study, the investigators intended to further characterise HPV negative cases of cervical intraepithelial neoplasia (CIN) 3 and cancers in a cohort of 511 women seen at a single centre over a two year period. Testing used Cervexbrush, Digene transport medium, and Hybrid Capture 2 DNA testing. There were 419 women with a biopsy diagnosis of CIN 3, of whom seven initially tested negative. Further review of these cases showed CIN 3 was not confirmed in two women, the specimen had no chromosomal DNA in two women, and HPV was actually present in three women. Among 92 cases of cervical cancer, seven were HPV-negative. On further review, four of these were found to be other cancers (endometrial, ovarian, bladder), and the remainder had no neoplastic tissue.
Bottom line In this German cohort of more than 500 women with biopsy results showing CIN 3 and cervical cancer, DNA tests for human papillomavirus were positive in more than 99% of cases. Patients with negative results on DNA testing were unlikely to have cervical cancer.
Level of evidence 1b (see www.infopoems.com/resources/levels.html); individual inception cohort study with > 80% follow up.
Bohmer G, van den Brule AJC, Brummer O, Meijer CJLM, Petry KU. No confirmed case of human papillomavirus DNA-negative cervical intraepithelial neoplasia grade 3 or invasive primary cancer of the uterine cervix among 511 patients. Am J Obstet Gynecol 2003;189: 118-20.
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Patient-Oriented Evidence that Matters. See editorial (BMJ 2002;325: 98312411333)
