{"doi":"10.1002/lary.25236","title":"What is the role of human papillomavirus testing in head and neck cancer?","abstract":null,"journal":"The Laryngoscope","year":2015,"id":624752,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1615144,"name":"Karam W. Badran","orcid":null,"position":1,"is_corresponding":false},{"id":702359,"name":"Maie A. St. John","orcid":"0000-0001-7068-9534","position":2,"is_corresponding":false},{"id":499467,"name":"Edward C. Kuan","orcid":"0000-0003-3475-0718","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"What is the role of human papillomavirus testing in head and neck cancer?","abstract":"Recently, human papillomavirus (HPV) has received much attention and interest due to its role in the pathogenesis of a subset of head and neck squamous cell carcinoma (HNSCC). HPV-positive HNSCC is especially interesting, in that it appears to be associated with improved survival with nonsurgical treatment modalities.1, 2 Traditional chemoradiotherapy for advanced HNSCC, though effective, can be acutely and chronically morbid for patients. The use of “de-escalated” treatment protocols, in which the intensity of chemoradiotherapy is reduced to minimize side effects, are currently being studied in HPV-positive HNSCC patients to optimize treatment outcomes while preserving quality of life.3 Thus far, no formal guidelines exist for selecting HNSCC patients who would be appropriate candidates for HPV testing. Incidentally, the vast majority of patients enrolled in randomized clinical trials for advanced HNSCC have oropharyngeal primaries1; as such, HPV-positive oropharyngeal HNSCC has been the most well-studied subsite. Many studies in the literature combine multiple HNSCC subsites when determining treatment outcomes, without stratifying outcomes by subsite. This creates significant confounding bias, as HNSCC can originate from a diverse number of other subsites that may behave differently. In light of this new development within the field of head and neck oncology, would it be appropriate to test all HNSCC patients for HPV as a positive predictor of treatment outcome? The prevalence of HPV positivity in oropharyngeal HNSCC patients has been estimated to be as high as 65%.1, 2 Numerous prospective, randomized controlled trials as well as retrospective studies have demonstrated significantly improved locoregional disease control and overall survival in HPV-positive oropharyngeal HNSCC following radiation or chemoradiation (>80%–90% at 2–3 years post-treatment).1, 2, 4 In several published studies, the inclusion of oropharyngeal HNSCC patient data into the analysis tends to overestimate positive outcomes. This can be attributed to both the actual improved outcomes in patients with HPV-positive oropharyngeal HNSCC, as well as to the overwhelming prevalence of oropharyngeal cancers relative to other subsites included. Patients with HPV-positive oropharyngeal carcinoma (with the exception of those with advanced tumor and/or nodal stage and a positive smoking history),1 would likely benefit from de-escalated treatment protocols, and thus, HPV testing would be indicated for all cases. This is especially true because of the known high prevalence of HPV among oropharyngeal HNSCC. Several studies have attempted to explore the relationship between HPV status and treatment outcomes in nonoropharyngeal HNSCC. A prospective randomized control trial by Ang et al.1 examined treatment outcomes following administration of cisplatin and accelerated or standard-fractionated radiotherapy in all HNSCC patients. When the subsites were combined, no significant difference in the rate of 3-year survival was identified (70.3% vs. 64.3%, P = .18). However, on retrospective analysis, those patients with HPV-positive oropharyngeal cancer had better overall survival rates (82.4%) than HPV-negative patients (57.1%, P < .001). In Fakhry et al.'s landmark prospective study, HNSCC patients with both oropharyngeal and laryngeal primaries were included in the analysis.2 Although 38 out of 60 (63%) oropharyngeal primaries tested positive for HPV, none of the 34 laryngeal primaries were positive.2 HPV-positive patients had improved 2-year overall (95% vs. 62%) and progression-free survival (86% vs. 53%) outcomes compared to HPV-negative patients when subtypes were combined and when the oropharyngeal subtype was assessed alone (P = .005). Of note, survival outcomes for patients with HPV-negative oropharyngeal cancer and patients with HPV-negative laryngeal cancer were similar to one another. Wilson et al. investigated treatment outcomes in all pharyngeal primary types (i.e., oropharyngeal, hypopharyngeal, nasopharyngeal) following radiation or chemoradiation.4 Although post-treatment survival was improved across all pharyngeal primaries when HPV status was positive, hypopharyngeal and nasopharyngeal primaries in isolation did not appear to bestow any survival benefit (overall 3-year survival 73% HPV+ vs. 73% HPV− for hypopharyngeal, 80% HPV+ vs. 75% HPV− for nasopharyngeal). Furthermore, in a retrospective histopathologic study by Stephen et al. examining HPV status in patients diagnosed with laryngeal HNSCC cases treated with surgery, radiation, chemotherapy, or chemoradiation, 21 of 79 (27%) cases were positive for HPV. HPV positivity was found to correlate with a slightly longer survival (nearly 80 months) when compared to HPV negativity (75 months), though this difference was not statistically significant.5 Due to lack of demonstrable survival benefit, these patients would thus not be appropriate candidates for de-escalated therapy based on current evidence. HPV testing should be performed for all HNSCC patients with an oropharyngeal primary site, with the goal to determine candidacy for de-escalated therapy.3 There is currently no evidence suggesting any benefit from HPV testing of other HNSCC primary sites, and thus, no recommendation can be made. A more sophisticated understanding of the pathogenesis of HNSCC and the causative role of HPV, as well as quality of life and survival outcomes from de-escalated therapy trials, will enable the head and neck oncologic community to solidify formal guidelines for HPV testing. Recommendations for HPV testing for oropharyngeal HNSCC are based on a prospective randomized controlled trial1 (level 1 evidence), a prospective cohort study2 (level 2 evidence) and retrospective reviews3-5 (level 3 evidence).","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25779218","pmcid":null,"openalex_id":"https://openalex.org/W2159954396","authors":[],"funders":[],"total_grants":0,"fwci":0.2355,"citation_percentile":0.56109302,"influential_citations":0,"citation_trend":[{"year":2016,"count":1}],"oa_status":"bronze","license":"http://doi.wiley.com/10.1002/tdm_license_1.1","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/lary.25236","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/lary.25236","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Flary.25236","host_type":"publisher"},{"url":"https://doi.org/10.1002/lary.25236","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25779218","host_type":"repository"}],"fields_of_study":["Head and Neck Cancer Studies","Head and Neck Surgical Oncology","Lung Cancer Treatments and Mutations"],"mesh_terms":["Carcinoma, Squamous Cell","Head and Neck Neoplasms","Humans","Practice Guidelines as Topic","Papillomaviridae","Papillomavirus Infections","Chemoradiotherapy"],"keywords":["Medicine","Head and neck squamous-cell carcinoma","Oncology","Head and neck cancer","Chemoradiotherapy","Internal medicine","Human papillomavirus","Clinical trial","Surrogate endpoint","Randomized controlled trial","Cancer"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-04T04:45:52.390078Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}