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
. 2024 Feb;13(3):e6916.
doi: 10.1002/cam4.6916. Epub 2024 Jan 21.

A systematic literature review of the human papillomavirus prevalence in locally and regionally advanced and recurrent/metastatic head and neck cancers through the last decade: The "ALARM" study

Sofia Agelaki  1   2 , Ioannis Boukovinas  3 , Ilias Athanasiadis  4 , Georgios Trimis  5 , Ioannis Dimitriadis  5 , Lazaros Poughias  5 , Edith Morais  6 , Ugne Sabale  7 , Goran Bencina  8 , Charalampos Athanasopoulos  5
Affiliations

A systematic literature review of the human papillomavirus prevalence in locally and regionally advanced and recurrent/metastatic head and neck cancers through the last decade: The "ALARM" study

Sofia Agelaki et al. Cancer Med. 2024 Feb.

Abstract

Aims: The aim of this systematic literature review was to provide updated information on human papillomavirus (HPV) prevalence in locally and regionally advanced (LA) and recurrent/metastatic (RM) head and neck cancer (HNC) worldwide.

Methods: Electronic searches were conducted on clinicaltrials.gov, MEDLINE/PubMed, Embase, and ASCO/ESMO journals of congresses for interventional studies (IS; Phase I-III trials) as well as MEDLINE and Embase for non-interventional studies (NIS) of LA/RM HNC published between January 01, 2010 and December 31, 2020. Criteria for study selection included: availability of HPV prevalence data for LA/RM HNC patients, patient enrollment from January 01, 2010 onward, and oropharyngeal cancer (OPC) included among HNC types. HPV prevalence per study was calculated as proportion of HPV+ over total number of enrolled patients. For overall HPV prevalence across studies, mean of reported HPV prevalence rates across studies and pooled estimate (sum of all HPV+ patients over sum of all patients enrolled) were assessed.

Results: Eighty-one studies (62 IS; 19 NIS) were included, representing 9607 LA/RM HNC cases, with an overall mean (pooled) HPV prevalence of 32.6% (25.1%). HPV prevalence was 44.7% (44.0%) in LA and 24.3% (18.6%) in RM. Among 2714 LA/RM OPC patients from 52 studies with available data, mean (pooled) value was 55.8% (50.7%). The majority of data were derived from Northern America and Europe, with overall HPV prevalence of 46.0% (42.1%) and 24.7% (25.3%) across studies conducted exclusively in these geographic regions, respectively (Northern Europe: 31.9% [63.1%]). A "p16-based" assay was the most frequently reported HPV detection methodology (58.0%).

Conclusion: Over the last decade, at least one quarter of LA/RM HNC and half of OPC cases studied in IS and NIS were HPV+. This alarming burden is consistent with a potential implication of HPV in the pathogenesis of at least a subgroup of HNC, underscoring the relevance of HPV testing and prophylaxis to HNC prevention and management.

Keywords: cancer prevention; cancer risk factors; epidemiology and prevention; head and neck cancer; viral oncology.

PubMed Disclaimer

Conflict of interest statement

Sofia Agelaki is a member of the executive board of the Hellenic Society of Medical Oncology, has served as an investigator in clinical studies for MSD Greece, has received consulting fees for participating in Expert Input Forums for MSD Greece, and has received lecture honoraria by MSD Greece. Ioannis Boukovinas, former president of the Hellenic Society of Medical Oncology, has served as an investigator in clinical studies for MSD Greece, has received consulting fees for participating in Advisory Boards for MSD Greece, has received lecture honoraria by MSD Greece, and has received support for attending international congress from MSD Greece. Ilias Athanasiadis has served as an investigator in clinical studies for MSD Greece, has received consulting fees for participating in Advisory Boards for MSD Greece, has received lecture honoraria by MSD Greece, and has received support for attending international congress from MSD Greece. Georgios Trimis, Ioannis Dimitriadis, Lazaros Poughias, and Charalampos Athanasopoulos are employees of MSD Greece and own stock in Merck & Co., Inc., Rahway, NJ, US. Edith Morais is an employee of MSD France and owns stock in Merck & Co., Inc., Rahway, NJ, US. Sabale Ugne is an employee of MSD Sweden and owns stock in Merck & Co., Inc., Rahway, NJ, US. Goran Bencina is an employee of MSD Spain and owns stock in Merck & Co., Inc., Rahway, NJ, US.

Figures

FIGURE 1
FIGURE 1
PRISMA diagrams for selection of (A) interventional studies and (B) non‐interventional studies. HN, head and neck; HNC, head and neck cancer; HPV, human papilloma virus; n, number of studies; OPC, oropharyngeal cancer; OPX, oropharynx. †Number of excluded articles per reason does not add up to total number of excluded articles as many cases were excluded for more than one reason.
FIGURE 2
FIGURE 2
HPV prevalence in LA and RM HNC, OPC fraction, and HPV prevalence in LA and RM OPC. HNC, head and neck cancer; HPV, human papilloma virus; IS, interventional studies; LA, locally and regionally advanced; N, number of patients; NA, not applicable; n/a, not available; NIS, non‐interventional studies; OPC, oropharyngeal cancer; RM, recurrent and/or metastatic. Circle size corresponds to number of patients included in the study indicated, ranging from 6 to 882 patients across 81 studies in HNC, and from 3 to 447 patients across 52 studies in OPC. Overall HPV prevalence is provided as mean and pooled HPV prevalence across studies and depicted as a black and red diamond, respectively. Overall OPC fraction is provided as mean and pooled OPC fraction across studies as a black and red bar, respectively.
FIGURE 3
FIGURE 3
HPV prevalence by number of HNC cases in each study. HPV, human papilloma virus; N, number of enrolled HNC patients. HPV prevalence from studies included in the evidence synthesis is plotted against each study's size. To visualize distribution of studies around the overall HPV prevalence and potential effect of sample size, estimated mean, median, and pooled HPV prevalence across studies are provided in dotted lines.
See this image and copyright information in PMC

References

    1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209‐249. doi:10.3322/caac.21660 - DOI - PubMed
    1. Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR. Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2020;6(1):92. doi:10.1038/s41572-020-00224-3 - DOI - PMC - PubMed
    1. Syrjänen K, Syrjänen S, Lamberg M, Pyrhönen S, Nuutinen J. Morphological and immunohistochemical evidence suggesting human papillomavirus (HPV) involvement in oral squamous cell carcinogenesis. Int J Oral Surg. 1983;12(6):418‐424. doi:10.1016/s0300-9785(83)80033-7 - DOI - PubMed
    1. International Agency for Research on Cancer . Human papillomaviruses. IARC Monogr Eval Carcinog Risks Hum. 2007;90:1‐636. - PMC - PubMed
    1. Götz C, Bischof C, Wolff KD, Kolk A. Detection of HPV infection in head and neck cancers: promise and pitfalls in the last ten years: a meta‐analysis. Mol Clini Oncol. 2019;10(1):17‐28. doi:10.3892/mco.2018.1749 - DOI - PMC - PubMed

Publication types