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own, though they did correspond to better oropharyngeal cancer survival when
found together with positive blood tests for E6 and E7. Based on these fi ndings, it is
concluded that a stronger association of HPV presence with prognosis (assessed by
all-cause survival) is observed when HPV-associated HNSCC is defi ned using
tumor status (HPV DNA or P16) and HPV E6/E7 serology in combination rather
than using tumor HPV status alone (Liang et al. 2012 ).
Another study on oropharyngeal squamous cell carcinomas (OPSCC) found its
own evidence arguing against the use of HPV DNA as a solo biomarker for HPV-
associated cancer (Holzinger et al. 2012 ). They authors tested OPSCC tumors for
HPV DNA and p16. They also considered the viral load in the tumors and looked
for gene expression profi les resembling those described in cervical carcinoma,
another cancer associated with HPV infection. Again, the presence of HPV DNA
appeared to be a poor indicator of HPV-associated cancers or predictor of cancer
outcomes. Whereas nearly half of the tumors tested positive for HPV16 DNA, just
16 % and 20 % had high viral loads and cervical cancer-like expression profi les,
respectively. The researchers found that a subset of HPV DNA-positive tumors with
high viral load or HPV-associated expression patterns belonged to individuals with
better outcomes. In particular, they found that cervical cancer-like expression pro-
fi les in OPSCC tumors coincided with the most favorable outcomes, while high
viral load in the tumors came a close second. Once standardized assays for these
biomarkers, applicable in routine clinical laboratories, are established, they will
allow precise identifi cation of patients with oropharyngeal cancer with or without
HPV-driven cancers and, thus, will infl uence prognosis and potentially treatment
decisions. More research is needed to understand whether the patterns described in
the new studies hold in other populations and to tease apart the prognostic impor-
tance of HPV infection in relation to additional prognostic biomarkers.
Personalized Management of Hematological Malignancies
Myeloproliferative disorders include several pathologies sharing the common fea-
ture of being clonal hematopoietic stem cell diseases. Hematological malignancies
are highly heterogeneous in the matter of molecular mechanisms related to their
development and progression. A considerable heterogeneity can be further observed
within the same disease at the interindividual level as refl ected by different clinical
outcomes and responses to treatment in different patients. Considerable work has
been done on molecular cytogenetics of hematological malignancies and a number
of diagnostics and therapies are available or under development.
The molecular basis of chronic myeloid leukemia (CML) was characterized
many years ago with the discovery of the t(9;22) translocation and its product the
BCR-ABL oncoprotein. The fi nding of a recurrent mutation in the Janus 2 tyrosine
kinase (JAK2) gene was a major advance in understanding of the pathogenesis of
several other myeloproliferative disorders, including polycythemia vera, essential
thrombocythemia and idiopathic myelofi brosis. Such a recurrent and unique
10 Personalized Therapy of Cancer