A comprehensive review of Hep-2 cell line in translational research for laryngeal cancer

Abstract

Cell lines represent an invaluable resource in modern science including basic and translational cancer research. Although there have been warnings over the past half century, the number of publications in the literature that erroneously used "non-existent" cell lines is still growing. For example, the Hep-2 cell line, first described in 1954 as laryngeal cancer cells, was reported as soon as in 1966 to be comprised of cervical adenocarcinoma cells derived via HeLa cell line contamination. Notably, the International Cell Line Authentication Committee (ICLAC) reported Hep-2 to be one among 488 misidentified cell lines, and one of 451 cell lines where no authentic stock is known. However, the number of laryngeal cancer research publications using the Hep-2 cell line has greatly increased over the past three decades. A comprehensive review of Hep-2 cell line misuse has been performed to identify the extent of the problem. 1,036 publications referenced in the MEDLINE database from 1954 to the first of January 2018 referred to the purported laryngeal origin of the Hep-2 cell line, with an increasing trend and with a peak of 93 publications in 2014. The rate of publications that focused on laryngeal cancer topics have increased over the past three decades to reach 80% in 2017. This increase was mainly driven by the remarkable productivity of Chinese researchers, of which English-language publications represented 76% of these articles in 2017. International collaborations and up-to-date national guidelines are needed.

Keywords: Cell line; HeLa; cancer research; laryngeal neoplasms; scientific misconduct.

Figure 1

The annual number of articles in the MEDLINE database referring to the Hep-2 cell line with or without stating its historically assumed laryngeal carcinoma origin.

Figure 2

The number of articles in the MEDLINE database referring to the Hep-2 cell line and its historically assumed laryngeal carcinoma origin, according to whether or not the laryngeal nature of the cells was directly relevant to the findings.

Figure 3

The number of English-language articles in the MEDLINE database citing the Hep-2 cell line and its historically assumed laryngeal carcinoma origin, according to the country of the corresponding author(s).