Journal of Clinical Virology - Volume 82 - Supplement 1 - September 2016

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Abstracts / Journal of Clinical Virology 82S (2016) S1–S142 S93
Abstract no: 33
Presentation at ESCV 2016: Poster 145
Vaginal intraepithelial neoplasia induced by
unusual papillomavirus subtype associated
with high load of human herpes virus 6
M. Pichon ∗, A. Gaymard , K. Lebail-Karval ,
E. Beaufils , G. Lamblin , G. Chene , B. Lina ,
T. Gheit , Y. Mekki
1 Virology Department, University Hospital of Lyon,
France
2 Virpath, Inserm U1111 – CNRS UMR 5308, Lyon,
France
3 Department of Gynecological Surgery and
Oncology, Obstetrics, University Hospital of Lyon,
France
4 Infections and Cancer Biology Group, International
Agency for Research on Cancer, Lyon, France
Introduction: Newly developedmolecular technics has allowed
the description of hundreds human papillomavirus (HPV) sub-
types. These viruses are linked to mucosal and cutaneous lesions
and cause 4.8% of cancer worldwide. After integration in basal
squamous cells, HPV remains non-activated until production of
oncoproteins. The main HPV-induced cancers (cervix, penis, vulva,
vagina, anus and pharynx) are caused by different HPV subtypes
justifying an orientated HPV subtyping to detect High-risk (mainly
HPV-16 and 18) or Low risk HPVs. We report here an atypical case of
Vaginal Intra-epithelial Neoplasia (VaIN) linked to HHV6 and HPV 4
co-infection.
Case report: In 2008, a 54 years-old woman presented during
a systematic cervical smear a Low grade Squamous Intraepithelial
Lesion (SIL). HPV screening of this sample remained negative using
routine technics which screen 16 of the most frequent HPV sub-
types (CLART HPV, Genomica, Spain). This patient was put under
surveillance to assess the evolution of the lesions. Four years later,
the lesions had developed to High grade – SIL (Cervical Intra epithe-
lial Neoplasia grade 2) and metrorrhagia shad appeared. After a
non-contributory colposcopy, the suspect area of the cervix was
resected and multiple Iodo-negative maculas in the vagina were
biopsied analysed and classified as VaIN grade 2 by pathologists. All
samples taken during the resection remained HPV-negative using
the routine screening test. A wide screening for papillomaviridae
and polyomaviridae was done on all samples to explain the dis-
cordance between clinical signs and HPV-negative screening test.
Twelve polyomaviridae and 101 HPV subtypes were tested but only
HPV4 was found with a significant viral load. All Herspesviridae
were also screened and a very high load of the HHV6 subtype A
was found in the samples. So the HHV6 and HPV4 co-infection was
hold liable for the VaIN. Six months later, the remaining lesions
were removed by laser techniques leading to the patient’s recov-
ery. The patient immunity was analysed (complete blood count,
protein electrophoresis, immunoglobulins dosage) but showed no
abnormalities.
Discussion: HPV4 is mostly associated to sun exposed skin can-
cer like basal cell carcinoma and most of the patients showing
these types of non-melanoma skin cancer are immunosuppressed
patients. After all, our patient did not present a systemic immun-
odepression. However, a local immunosuppression could be linked
to this clinical emergence of the neoplasia. Indeed, very high local
concentrations of HHV6, which target lymphocytes T helpers, may
induce severe and local immunosuppression which enhances the
oncogenic virus replication. Papillomaviridae represent a heteroge-
neous virus family, with more than 200 different subtypes and it is
assumed that most of them remain to be discovered. This case high-
lights the need for a global approach without a priori in the field
of virus-inducted cancers. New technologies like deep sequenc-
ing, Whole-Genome Sequencing or multiplex syndromic approach
could bring very precious data and help elucidate numerous com-
plicated cases as the one we described here.
Abstract no: 34
Presentation at ESCV 2016: Poster 146
Inflammatory cytokine and gene expression
patterns correlate with etiologic agent causing
pneumonia among patients with advanced HIV
in Medellin, Colombia
Yoav Keynan ∗, Adriana Trajtman ,
Paul McLaren dy Aguilar aro Velez
Zulma V. Rueda
1 University of Manitoba, Canada
2 University of Manitoba, PHAC, Canada
3 Universidad de Antioquia UdeA, Medellin, Colombia
4 Universidad Pontificia Bolivariana, Medellin,
Colombia
Objectives: A role for the magnitude of the inflammatory
response in clinical course and outcomes has been suggested in
patients with HIV. During acute pneumonia, migrating neutrophils
and alveolar macrophages secrete a myriad of chemotactic fac-
tors and pro-inflammatory cytokines that include reactive oxygen
species, IL-8, IL-2 , IL-6, IL-17, TNF among others. We sought
to determine the inflammatory cytokine and gene expression sig-
natures associated with the pathogen (fungal, tuberculosis and
bacterial) among patients with advanced HIV, presenting with
pneumonia in Medellin, Colombia.
Methods: Patients admitted with pneumonia were enrolled
in the study. After informed consent, demographic, clinical and
laboratory information was collected. Individuals underwent
bronchoscopy and Bronchoalveolar Lavage (BAL) obtained when
deemed necessary by the clinical caregiver team. BALs were spun
down and supernatant used for multiplex cytokine/chemokine
bead arrays, measuring the concentrations of 19 cytokines and
chemokines. We adapted RNA-Seq techniques to measure gene
expression in BAL. We performed univariate, multivariate and
Principal Component Analysis (PCA) to identify proinflammatory
profiles that were correlatedwith fungal, tuberculosis and bacterial
pneumonia and we analysed the differentially expressed proin-
flammatory genes associated with the TB or Fungal infections.
Results: Among 57 patients with HIV, The most frequent
pathogens identified by traditional methods were: M. tuberculosis
(40.4%), Fungi (Pneumocystis jirovecii, Histoplasma, and Cryptococ-
cus) (42.2%), Bacteria (8.8%). Using PCA analysis we identified
distinct patterns of BAL cytokines associated with fungal infections
and Mycobacterium tuberculosis infection. We identified genes that
are over expressed among patients with TB as the causative agent
of pneumonia.
Conclusion: Distinct cytokine/chemokine and inflammatory
gene expression patterns are associated with the etiology of pneu-
monia among HIV infected individuals. These cytokine/chemokine
and inflammatory genes may be utilized as biomarkers for etiologi-
cal diagnosis. In addition, identifying the insight into the inflamma-
tory pathways associated with each pathogen may provide targets
for adjunct anti-inflammatory therapy to decrease lung injury.