*Re-upload of slides originally posted 27th January 2019* A presentation describing cancer of unknown primary (CUP), specifically in the head and neck region, its relation to human papillomavirus-associated OP cancer, and the clinical relevance of this link. Slides compiled as part of medical school studies. Sources for all imagery and sources listed in references section where possible. I do not claim ownership of any images or graphics. Slides for educational purposes only, and should not replace clinical judgement. No monetary gain was made for this work.

1. and its relation to HPV-associated
oropharyngeal cancer
Robert Ferris

2.  Sometimes referred to as “occult primary
cancer”
 Metastatic spread from an unknown origin
 Primary cancer is
often never
identified

3.  Because CUP is spread from an unknown
source, diagnosis of cancer type relies
entirely on histology and other lab tests (e.g.
PCR, immunohistochemistry)
 This ambiguity as to the type and
characteristics of a given cancer can make it
extremely difficult to find an effective
treatment plan. Additionally, the nature of
CUP means that it is often only detected once
widespread metastasis has occurred, so
prognosis is often very poor.1

4. 6

5.  Papillomaviridae: non-enveloped, DS DNA
 Low risk: HPV 6, 11 → condyloma acuminata

6. ‣ High risk: HPV 16,18 → carcinoma

7.  Cervical cancer the overwhelming majority2
 Various other sites are also susceptible
 Oropharynx common3
, and a roughly 70% of
OP cancers are
linked with
HPV infection4

8.  OP cancers, as well as other forms of Head
and Neck Squamous Cell Carcinoma (HNSCC)
are treated according to the stage and the
characteristics of the disease, usually
requiring some combination of:
 Surgery
 Radiation
 Chemotherapy
 Molecularly targeted therapies are used for
specific cancer types; HPV-associated cancers
have an improved prognosis and survival
rates when compared with other HNSCCs.5

9.  If CUP types can be more readily identified
then targeted, effective treatment plans can
be implemented sooner.
 With this in mind, there has been much
research into potential links between HPV and
CUP of the head and neck.

10.  HPV positivity found in many cases of head
and neck CUP6,7,8
 Strong correlation between HPV positivity and
CUP originating from OP carcinomas7

11.  HPV status is a useful diagnostic and
prognostic indicator in some CUPs of the
head and neck7,8,10
 HPV-status useful for developing specific
treatment plan, which can lead to better
outcomes9
 HPV status can also be combined with other
factors (e.g. tobacco use) to develop clearer
predictions of survival in patients with CUP10

12. References:
1. Varadhachary, G. and Raber, M. (2014). Cancer of Unknown Primary
Site. New England Journal of Medicine, 371(8), pp. 757–765
2. Crow, J. (2012). HPV: The global burden. Nature, 488(S2-S3)
3. Parkin, D. And Bray, F. (2006). Chapter 2: The burden of HPV-
related cancers. Vaccine, 24(S3), pp. 11-25
4. Chaturvedi AK., Engels EA., Pfeiffer RM., et al. (2011). Human
papillomavirus and rising oropharyngeal cancer incidence in the
United States. Journal of Clinical Oncology, 29(32), pp.4294–4301
5. Ang K., Harris J., Wheeler R., et al. (2010). Human papillomavirus
and survival of patients with oropharyngeal cancer. New England
Journal of Medicine, 63(1), pp. 24-35
6. National Cancer Registration and Analysis Service (NCRAS). (2010).
Diagnosis and management of metastatic malignant disease of
unknown primary origin,
https://www.nice.org.uk/guidance/cg104/evidence/full-guideline-
pdf-134697133 [Accessed 26/01/2019]

13. References (cont.):
6. Theodoraki, M., Veit, J., Hoffmann, T. and Greve, J. (2017).
Synchronous bilateral tonsil carcinoma: case presentation and
review of the literature. Infectious Agents and Cancer, 12(38)
7. Zengel, P., Assmann, G., et al. (2012). Cancer of unknown primary
originating from oropharyngeal carcinomas are strongly correlated
to HPV positivity. Virchows Archiv, 461(3), pp.283-290
8. Sivars, L., Tani, E., Näsman, A., Ramqvist, T., Munck-Wikland, E.
and Dalianis, T. (2016). Human Papillomavirus as a Diagnostic and
Prognostic Tool in Cancer of Unknown Primary in the Head and
Neck Region. Anticancer Research, 36(2), pp. 487-493
9. Yasui, T., Morii, E., et al. (2014). Human Papillomavirus and Cystic
Node Metastasis in Oropharyngeal Cancer and Cancer of Unknown
Primary Origin, PLOS ONE, 9(12):
e116030. https://doi.org/10.1371/journal.pone.0116030
[Accessed 26/01/2019]
10. Tribius, S., Hoffmann, A., et al. (2012). HPV status in patients with
head and neck of carcinoma of unknown primary site: HPV,
tobacco smoking, and outcome. Oral Oncology, 48(11), pp. 1178-
1184