Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Dec:2:133-140.
doi: 10.1016/j.pvr.2016.07.002. Epub 2016 Jul 16.

Low prevalence of HPV-driven head and neck squamous cell carcinoma in North-East Italy

Lorena Baboci  1 , Dana Holzinger  2 , Paolo Boscolo-Rizzo  3 , Giancarlo Tirelli  4 , Roberto Spinato  5 , Valentina Lupato  6 , Roberto Fuson  7 , Markus Schmitt  8 , Angelika Michel  9 , Gordana Halec  10 , Maria Cristina Da Mosto  11 , Michael Pawlita  12 , Annarosa Del Mistro  13
Affiliations

Low prevalence of HPV-driven head and neck squamous cell carcinoma in North-East Italy

Lorena Baboci et al. Papillomavirus Res. 2016 Dec.

Abstract

Objectives: To investigate the frequency of Human papillomavirus (HPV)-driven head and neck squamous cell carcinoma (HNSCC) among patients living in North-East Italy, by assessing HPV-DNA positivity in all tumors and additional markers whenever possible.

Material and methods: HPV types, viral load, viral RNA, HPV16/18 E6 protein and p16INK4a and pRb expression were determined in primary tumor tissues from 247 HNSCC patients. Tumor-specific HPV seropositivity was analyzed in 102 patients.

Results: Tumor HPV-DNA prevalence was 8.5% overall (21/247) and 27% in oropharynx (17/63). HPV16 accounted for 95% of all HPV types found. Among HPV-DNA+ tumors, type-concordant HPV E6*I RNA prevalence was 79%. HPV DNA+ RNA+ tumors showed high viral load, up-regulated p16INK4a, down-regulated pRb and presence of HPV16 E6 protein. Eight cases showed tumor-specific HPV seropositivity, all type-concordant with the tumor. Tumors were defined as HPV-driven when positive for HPV-DNA plus 2 additional HPV transformation-related markers.

Conclusion: Relative prevalence of HPV-driven tumors (14 HPV16, 1 HPV58) was 6% overall and 20% among oropharyngeal cancers. In the oropharynx the HPV-driven group showed a trend for better survival versus the HPV-negative group. The relative prevalence of HPV-driven oropharyngeal cancer is low in North-East Italy as compared to Western and Northern Europe.

Keywords: HPV antibodies; HPV-driven; HPV-related markers; Head and neck cancer; Oropharyngeal cancer; Prevalence.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Flow chart of the most significant analyses (i.e. E6*I mRNA RT-PCR,HPV viral load by HPV16 ultrashort-qPCR or MPG MFI, and p16 IHC) performed on the tumors of the 247 HNSCC enrolled patients, by HPV-DNA status. 138/247 (56%) samples were double tested for HPV-DNA by BSGP5+/6+-PCR/MPG51 (MPG) and MY09/MY11-RFLP (MY), and 109/247 (44%) by MY only. HPV++ and HPV−−: sample positive or negative by both methods; HPV+ and HPV−: sample positive or negative by one method only. HPV+− and HPV−+: sample positive/negative or negative/positive by MPG and MY, respectively. Overall, 3 cases were discordant (2 HPV+− and 1 HPV−+); considering that the MPG sensitivity is higher compared to the MY assay, the 2 HPV+− and 1 HPV−+ were considered as positive and negative, respectively. HPV16high: >0.1 HPV16 copies per cell; HPV16low: <0.1 HPV16 copies per cell. p16 high: nuclear and cytoplasmic signal present in most tumor cells.
Fig. 2
Fig. 2
Overall and site specific HPV DNA and RNA prevalence among all head and neck tumors and stratified by anatomical site. Overall, 247 tumors were analyzed for HPV DNA, 63 from the oropharynx, 63 from the oral cavity, 96 from the larynx, and 25 from the hypopharynx. Of the 21 HPVDNA positive tumors, 18 were analyzed for HPV RNA, while 3 (2 from oropharynx and 1 from larynx) could not be analyzed.
Fig. 3
Fig. 3
A. Overall survival (OS) and B. Progression free survival (PFS) of OPSCC patients by HPV-driven and HPV non-driven status (assessed in 61/63 cases). The continuous line refers to patients with HPV-driven OPSCC, the dotted line refers to patients with HPV-non driven OPSCC. The patients with HPV-driven tumors showed a trend (P=0.09) for better OS (A) and a significant (P=0.016) difference for PFS (B).
See this image and copyright information in PMC

References

    1. J. Ferlay, E. Steliarova-Foucher and J. Lortet-Tieulent et al., Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012, Eur. J. Cancer 49, 2013, 1374–1403 - PubMed
    1. Ndiaye C., Mena M., Alemany L. HPV DNA, E6/E7 mRNA, and p16INK4a detection in head and neck cancers: A systematic review and meta-analysis. Lancet Oncol. 2014;15(12):1319–1331. - PubMed
    1. IARC. Human papillomaviruses. IARC Monogr Eval Carcinog Risks Hum 2011; 100B: 1–475. A review of human carcinogens—Part B: biological agents, vol. 100B, 2011. IARC Monogr Eval Carcinog Risks Hum 100B (2011) 1–475.
    1. Chaturvedi A.K., Anderson W.F., Lortet-Tieulent J. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J. Clin. Oncol. 2013;31:4550–4559. - PMC - PubMed
    1. Sturgis E.M., Ang K.K. The epidemic of HPV-associated oropharyngeal cancer is here: Is it time to change our treatment paradigms? J. Natl. Compr. Cancer Netw. 2011;9(6):665–673. - PubMed

Publication types