Three Cancers: Key Papers, Persistent Challenges

May 2013

More than 17,000 people attended the 2012 American Association for Cancer Research (AACR) meeting, a firm fixture in the oncology calendar. The schedule for this year’s meeting, in Washington, D.C., offered opportunities to catch up on many oncological topics, including some that have caught the eye of ScienceWatch and Thomson Reuters citation analysts in recent years

The accompanying table turns to Thomson Reuters Web of Knowledge to provide the citation status for a few key papers on three such topics, while the text below contains short updates of the same research areas, taking into account papers that appeared in 2012 and 2013 to date and, therefore, have not yet attracted many citations.

Key Papers on Selected Cancers, Published Since 2007

Prostate Cancer Screening

Paper Citations
F.H. Schröder, et al., “Screening and prostate-cancer mortality in a randomized European study,” New Engl. J. Med., 360(13):1320-8, 2009. 1,207
G.L. Andriole, et al., “Mortality results from a randomized prostate-cancer screening trial,” New Engl. J. Med., 360(13): 1301-9, 2009. 889

Treatments for Melanoma

Paper Citations
K.T. Flaherty, et al., “Inhibition of mutated, activated BRAF in metastatic melanoma,” New Engl. J. Med., 363(9): 809-19, 2010. 789

HPV Outside the Uterine Cervix

Paper Citations
G. D’Souza, et al., “Case-control study of human papillomavirus and oropharyngeal cancer,” New Engl. J. Med., 356(19): 1944-56, 2007. 645
SOURCE: Thomson Reuters Web of Knowledge


The depressing thing about screening for prostate cancer is how little the arguments have changed over the years. Labelling researchers and clinicians as “for” or “against” can be simplistic, but with the scheduled participation of Otis W. Brawley of the American Cancer Society (skeptic; see Ann. Intern. Med., 157[2]: 135-36, 2012) and Fritz H. Schröder, Erasmus University, Rotterdam (more enthusiastic; see BJU Int., 110[suppl 3-7], 2012) AACR coverage of prostate cancer screening promised to be lively.

The European (ERSPC) and US (PLCO) trials of screening by measurement of prostate-specific antigen (PSA) now have longer follow-up. The relative risk reduction for mortality from prostate cancer had risen from 21% in the first report (table) to an adjusted 29% at 11 years but in absolute terms this was a saving of 1 death for every 10,000 person-years (F.H. Schröder, et al. New Engl. J. Med., 366[11]: 981-90, 2012) while PLCO was, at 13 years, still reporting “no evidence of a mortality benefit” (G.L. Andriole, et al., J. Natl. Cancer Inst., 104[2]: 125-32, 2012). (These trials were discussed in ScienceWatch in 2010.)

The latest findings seem unlikely to change anyone’s views. Nor will the updated Cochrane Review published at the end of January, which confirms, for data from five randomized trials taken overall, no significant reduction in either all-cause or prostate-cancer specific mortality (D. Ilic, et al., Cochrane Database Syst. Rev. Epub Jan 31, 2013: DOI 1002/14651858.CD004720.pub3). Apart from the big question—does this screening save lives?—other controversies concern raised PSAs in the absence of cancer and the consequences of such false positives; the complications of the next step (biopsy); and the management of detected cancers that are localized to the prostate gland, choices that include radical prostatectomy and the more conservative policy of “watch and wait.” The answer to this last question that was provided last July by the PIVOT trial is “radical prostatectomy did not reduce all-cause or prostate-cancer mortality” (T.J. Wilt et al., New Engl. J. Med., 367[3]: 203-13, 2012). ERSPC’s main results have appeared in a general journal but much extra information from this trial can be found in the specialist literature—e.g., the importance of taking screening non-attendance into account (R. Kranse et al., J Med. Screen., Epub Feb 17, 2013).


The outlook for patients with metastatic melanoma improved with the 2010 publication by Keith T. Flaherty and colleagues (see table), but it soon emerged that resistance is a problem with the use of BRAF inhibitors, a topic reviewed very recently (R.J. Sullivan, K.T. Flaherty, Eur. J. Cancer, 49(6): 1297-3042, 2013). That BRAF inhibition is a significant advance over dacarbazine, the previous standard, has been confirmed—e.g., for dabrafenib by Hauschild and colleagues (A. Hauschild, et al., Lancet 380[9839]: 358-65, 2012) and a combination of BRAF inhibition and MEK inhibition with trametinib is now being tried (K.T. Flaherty, et al. New Engl. J. Med., 367[2]: 107-14, 2012).


In 2012 the journal Vaccine devoted a supplement (Vaccine, 30[suppl 5], 2012) to human papillomavirus (HPV) infections and related diseases. That those diseases might include cancers other than cervical cancer (see table) has been confirmed. The ARCAGE study (D. Anantharaman, et al., J Natl. Cancer Inst., 105(8): 536-45, 2013) revealed a strong association between HPV-16 and cancers of the oropharynx and oral cavity and a “marginal role” for HPV types 6 and 18. On the other hand, InterSCOPE provides limited evidence for an association with esophageal squamous-cell cancer (F. Sitas, et al., J Natl. Cancer Inst., 104[2]: 147-58, 2012).

A former deputy editor of The Lancet, David W. Sharp, M.A. (Cambridge), is a freelance writer living in Minchinhampton, Gloucestershire, U.K.

The data and citation records included in this report are from Thomson Reuters Web of ScienceTM. Web of ScienceTM is a registered trademark of Thomson Reuters. All rights reserved.