HPV-Positive Head and Neck Cancer (HPV+ HNSCC) — Disease Characteristics Research Report

Target Disease

• Disease Name: HPV-Positive Head and Neck Cancer (HPV+ HNSCC), with emphasis on HPV-positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC), the dominant clinical entity in most datasets.
• MONDO ID: Not retrieved in the available evidence corpus.
• Category: Virus-associated squamous cell carcinoma (upper aerodigestive tract), primarily oropharynx.

1. Disease Information

Overview (current understanding)

HPV-positive head and neck squamous cell carcinoma is a subset of HNSCC in which oncogenic high-risk HPV infection is an etiologic driver; clinically this is most strongly associated with oropharyngeal squamous cell carcinoma (tonsil and base of tongue). Single-cell and translational studies treat HPV+ OPSCC as a distinct disease entity with unique immune and molecular features and generally more favorable outcomes compared with HPV-negative OPSCC. (yan2024decipheringtheinterplay pages 1-2, ndon2023humanpapillomavirusassociatedoropharyngeal pages 1-3)

Abstract-quotable definition/epidemiology framing: - Yan et al. (2024) open with: “Human papillomavirus (HPV) infection has become an important etiological driver of oropharyngeal squamous cell carcinoma (OPSCC), leading to unique tumor characteristics.” (Published online 6 Aug 2024; https://doi.org/10.1007/s00262-024-03789-0) (yan2024decipheringtheinterplay pages 1-2)

Synonyms / alternative names

• HPV-associated head and neck squamous cell carcinoma
• HPV-mediated oropharyngeal squamous cell carcinoma
• HPV-positive oropharyngeal cancer / HPV-associated OPSCC

Key identifiers (ontologies)

The provided evidence did not include explicit ontology identifiers (ICD-10/ICD-11, MeSH, MONDO). Consequently, this section is incomplete for identifiers. The staging context emphasizes AJCC/UICC TNM 8th edition separation/stratification of HPV-associated OPSCC (via p16 surrogate testing), but the manual itself was not retrieved in full as a citable source in this run. (Craig et al. discuss TNM8 implications) (craig2019recommendationsfordetermining pages 1-2)

Evidence provenance

Evidence here is derived primarily from: - Aggregated resources (registry/SEER/NCDB-like cohorts and reviews) (kim2024aseerbasedanalysis pages 1-2, ndon2023humanpapillomavirusassociatedoropharyngeal pages 1-3) - Single-center retrospective cohorts (cleere2024hpvovertakessmoking pages 1-2) - Clinical trial registry entries (ClinicalTrials.gov) (NCT01898494 chunk 1, NCT02215265 chunk 1) - Molecular/translational datasets (single-cell RNA-seq) (yan2024decipheringtheinterplay pages 1-2)

2. Etiology

Disease causal factors

Primary cause: persistent infection with oncogenic high-risk HPV (especially HPV16) leading to malignant transformation of oropharyngeal mucosa. (ndon2023humanpapillomavirusassociatedoropharyngeal pages 1-3, wu2024deescalationstrategiesin pages 1-2)

Mechanistic causal factors (viral-host interactions): - Viral oncogenes E6 and E7 promote malignant transformation through canonical tumor suppressor interference (p53 and RB axis). Wu et al. explicitly summarize: “E6 was found to specifically degrade p53” and “E7 binds to the unphosphorylated region of retinoblastoma (Rb).” (wu2024deescalationstrategiesin pages 1-2)

Risk factors

• HPV exposure (sexually transmitted; oropharyngeal exposure linked to sexual behavior). OPSCC tumors driven by HPV contrast with conventional carcinogen-driven OPSCC (alcohol/tobacco). (yan2024decipheringtheinterplay pages 1-2, krsek2024thenextchapter pages 1-2)
• Tobacco/alcohol remain important external risk factors for HNSCC broadly, and for HPV-negative OPSCC in particular; HPV-negative OPSCC is “caused primarily by conventional carcinogens like alcohol or tobacco exposure.” (yan2024decipheringtheinterplay pages 1-2)

Protective factors

• Prophylactic HPV vaccination is the primary prevention strategy; Ndon et al. state: “HPV vaccination is currently the main preventative approach for HPV-associated oropharyngeal cancer.” (Published 13 Aug 2023; https://doi.org/10.3390/cancers15164080) (ndon2023humanpapillomavirusassociatedoropharyngeal pages 1-3)

Gene–environment / virus–environment interaction (evidence-supported components)

• HPV-negative vs HPV-positive disease reflects different etiologic exposures (tobacco/alcohol vs HPV). (yan2024decipheringtheinterplay pages 1-2)
• HPV integration biology (see Mechanisms) suggests a viral–host genome interaction that influences immune infiltration and outcomes. (tabatabaeian2024navigatingtherapeuticstrategies pages 1-2)

3. Phenotypes

Clinical presentation (limited by available evidence)

The retrieved texts emphasized epidemiology, diagnostics, immune biology, and treatment strategy rather than symptom frequencies. Nonetheless, several clinically relevant patterns were present:

• Nodal disease prominence (clinical behavior): HPV+ OPSCC often presents with clinically significant cervical nodal disease despite favorable prognosis (not quantified in the evidence corpus here).
• Treatment-related morbidity affecting quality of life: major toxicities motivating de-intensification include swallowing dysfunction and other head-and-neck functional sequelae. E3311 includes swallowing/QOL endpoints, and PATHOS explicitly centers swallowing function (MDADI). (NCT01898494 chunk 1, NCT02215265 chunk 1)

Quality of life impact (evidence-supported)

• PATHOS’ stated main objective: “To assess whether swallowing function can be improved … by reducing the intensity of adjuvant treatment protocols.” (NCT02215265 chunk 1)

Suggested HPO terms (expert-curated; not directly asserted with frequencies in the retrieved evidence)

• Dysphagia — HP:0002015
• Odynophagia — HP:0033050
• Cervical lymphadenopathy — HP:0000453
• Weight loss — HP:0001824
• Xerostomia (treatment-related, esp. radiotherapy) — HP:0000217
• Dysarthria — HP:0001260

Note: Frequencies and onset distributions were not extractable from the current evidence set.

4. Genetic/Molecular Information

Viral molecular drivers

• High-risk HPV, particularly HPV16, is the dominant subtype in OPSCC; Ndon et al. state: “an estimated 30% of oropharyngeal squamous cell carcinomas … are driven by HPV, with HPV16 being the most common subtype associated with malignancy.” (ndon2023humanpapillomavirusassociatedoropharyngeal pages 1-3)
• E6/E7 oncogene activity is central to oncogenic mechanism (p53/RB axis). (wu2024deescalationstrategiesin pages 1-2)

Viral integration status (clinically important subtype concept)

Tabatabaeian et al. describe three HPV genome states in tumors: “integrated … episomal … or a mixture,” and highlight outcome differences: “patients with HPV-positive head and neck cancers generally have a good prognosis except for a group of patients with fully integrated HPV who show worst clinical outcomes. Those patients present with lowered expression of viral genes and limited infiltration of cytotoxic T cells.” (Published online 20 Apr 2024; https://doi.org/10.1038/s41416-024-02655-1) (tabatabaeian2024navigatingtherapeuticstrategies pages 1-2)

Host genomic alterations

The current evidence set does not provide primary data on specific recurrent somatic driver frequencies (e.g., PIK3CA, TRAF3, CYLD) in HPV+ OPSCC. (Reference lists hint at these topics but without extractable numeric evidence.) (atique2024comprehensiveanalysisof pages 55-58, cleere2024hpvovertakessmoking pages 9-9)

Epigenetics

Not directly extractable from retrieved primary evidence; discussed as a general biomarker domain in diagnostic reviews. (krsek2024thenextchapter pages 1-2)

5. Mechanism / Pathophysiology

Causal chain (evidence-based backbone)

1. Exposure and infection of oropharyngeal mucosa with high-risk HPV (often HPV16). (ndon2023humanpapillomavirusassociatedoropharyngeal pages 1-3)
2. Viral oncogene expression (E6/E7) disrupts tumor suppressor pathways: p53 degradation and RB-axis interference. (wu2024deescalationstrategiesin pages 1-2)
3. Tumor evolution with distinct immune microenvironment, often immune-infiltrated (“immune hot” concept is widely discussed in this field; in the evidence here, the immune-rich TME is directly analyzed by single-cell methods). (yan2024decipheringtheinterplay pages 1-2)
4. Clinical phenotype: HPV+ OPSCC tends to have more favorable prognosis overall, but with heterogeneity (e.g., integration status, discordant biomarker subsets). (craig2019recommendationsfordetermining pages 1-2, tabatabaeian2024navigatingtherapeuticstrategies pages 1-2)

Immune microenvironment (2024 single-cell evidence)

Yan et al. performed scRNA-seq on HPV+ and HPV− OPSCC (3 tumors each + normal tonsil), finding: - “HPV+ OPSCC tumor cells manifest an enhanced interferon response and elevated expression of the major histocompatibility complex II (MHC-II)” (yan2024decipheringtheinterplay pages 1-2) - They identify “a CXCL13+CD4+ T cell subset …” and report that interaction with HPV+ tumor cells “amplifies CXCL13 and IFNγ release … fostering a pro-inflammatory TME.” (yan2024decipheringtheinterplay pages 1-2) - They also note real-world clinical limitation: “the actual response rates of [immune checkpoint blockade] … remained relatively low (approximately 20%).” (yan2024decipheringtheinterplay pages 1-2)

Pathways / processes (ontology suggestions)

GO Biological Process (examples): - Interferon-gamma-mediated signaling pathway — GO:0060333 (supported conceptually by IFNγ/interferon response findings) (yan2024decipheringtheinterplay pages 1-2) - Antigen processing and presentation of peptide antigen via MHC class II — GO:0002495 (MHC-II elevation) (yan2024decipheringtheinterplay pages 1-2) - Regulation of T cell activation — GO:0050863 (CXCL13+ CD4+ interactions) (yan2024decipheringtheinterplay pages 1-2)

Cell Ontology (CL) suggestions: - CD4-positive, alpha-beta T cell — CL:0000624 (yan2024decipheringtheinterplay pages 1-2) - Cytotoxic T cell (CD8+ T cell) — CL:0000625 (integration-associated reduced cytotoxic T infiltration concept) (tabatabaeian2024navigatingtherapeuticstrategies pages 1-2)

GO Cellular Component suggestions: - MHC protein complex — GO:0042611 (yan2024decipheringtheinterplay pages 1-2)

6. Diagnostics

Current standard concepts (tissue-based)

• p16 immunohistochemistry is widely used as a practical surrogate marker, but discordance exists (p16+ may not always indicate transcriptionally active HPV). Craig et al. emphasize TNM8’s use of p16 as surrogate and demonstrate prognostic misclassification when HPV is not transcriptionally active. (craig2019recommendationsfordetermining pages 1-2)

Quantitative performance evidence (2023)

Yang et al. compared Aptima HR-HPV E6/E7 mRNA testing on cytology specimens with p16 IHC on biopsies in 60 HNSCC patients (39 OPSCC): - “overall concordance rate … 95.0%” (yang2023aptimahrhpvtesting pages 1-2) - “sensitivity and negative predictive values … consistent at 100%” (Aptima and p16 IHC) (yang2023aptimahrhpvtesting pages 1-2) - “specificity and positive predictive values were 96.9% and 96.6% versus 93.8% and 93.3%, respectively.” (Aptima vs p16 IHC) (Published online 13 Dec 2022 in Acta Cytologica 2023; https://doi.org/10.1159/000527951) (yang2023aptimahrhpvtesting pages 1-2)

Clinical importance of p16/HPV discordance (2019, staging-relevant)

Craig et al. show that a p16+ but HPV− (transcriptionally inactive HPV) subgroup has significantly worse survival: - “Patients who tested p16+ but were HPV− (n = 20) had significantly reduced five-year survival (33%) compared to p16+ patients (77%) but not p16− patients (35%).” (craig2019recommendationsfordetermining pages 1-2) - They conclude these findings are relevant for de-escalation because p16-only staging can downstage biologically higher-risk patients. (craig2019recommendationsfordetermining pages 1-2)

Suggested diagnostic tests / biomarkers (evidence-based categories)

• p16 IHC (screening surrogate) (yang2023aptimahrhpvtesting pages 1-2)
• HPV E6/E7 mRNA assays (e.g., Aptima; RNA-based evidence of transcriptional activity) (yang2023aptimahrhpvtesting pages 1-2)
• HPV DNA and genotyping (PCR-based in Yan et al. patient classification; HPV DNA detection used to confirm HPV status) (yan2024decipheringtheinterplay pages 1-2)

7. Treatment

Standard modalities (current practice)

Standard treatment remains multimodal (surgery and/or radiotherapy ± chemotherapy), and HPV+ disease’s better prognosis has motivated attempts to reduce treatment morbidity while maintaining control. (krsek2024thenextchapter pages 1-2, wu2024deescalationstrategiesin pages 1-2)

De-intensification / risk-adapted treatment (real-world implementation: ongoing trials)

ECOG-ACRIN E3311 (NCT01898494; Phase II; p16+ locally advanced, resectable OPC) - Official title: “Phase II Randomized Trial of Transoral Surgical Resection Followed by Low-Dose or Standard-Dose IMRT in Resectable p16+ Locally Advanced Oropharynx Cancer” (NCT01898494 chunk 1) - Key design: all patients undergo transoral surgery, then risk stratification: - Intermediate-risk randomized: 50 Gy/25 fx vs 60 Gy/30 fx IMRT (NCT01898494 chunk 1) - High-risk: 66 Gy/33 fx IMRT + weekly cisplatin (days 1, 8, 15, 22, 29, 36, 43) (NCT01898494 chunk 1) - Enrollment: 519; status ACTIVE_NOT_RECRUITING; results posted 28 Sep 2022 (registry metadata). (NCT01898494 chunk 1)

PATHOS (NCT02215265; Phase III; post-operative risk-stratified adjuvant therapy after transoral surgery) - Official title: “A Phase III Trial of Risk-stratified, Reduced Intensity Adjuvant Treatment … HPV-Positive Oropharyngeal Cancer” (NCT02215265 chunk 1) - Objective includes swallowing/QoL and non-inferiority for survival: “To demonstrate the non-inferiority of reducing the intensity of adjuvant treatment protocols in terms of overall survival …” (NCT02215265 chunk 1) - Radiation de-escalation arms: - Group B: PORT 60 Gy/30 fx vs 50 Gy/25 fx (NCT02215265 chunk 1) - Group C: POCRT 60 Gy/30 fx + cisplatin vs PORT 60 Gy/30 fx without chemotherapy (NCT02215265 chunk 1) - Target enrollment increased to 1269 (protocol amendment March 2024). (NCT02215265 chunk 1)

Immunotherapy considerations

Despite immune infiltration in HPV+ OPSCC, checkpoint blockade responses are heterogeneous and “approximately 20%” in the Yan et al. framing, motivating deeper TME stratification and biomarker development. (yan2024decipheringtheinterplay pages 1-2)

Suggested MAXO terms (ontology suggestions)

• Radiotherapy — MAXO:0000027
• Chemotherapy — MAXO:0000077
• Surgical resection — MAXO:0000445
• Immunotherapy — MAXO:0000127
• Swallowing rehabilitation — MAXO:0000746

8. Outcome / Prognosis

Survival differences (HPV+ vs HPV−)

• In an Irish single-center cohort (2012–2021), HPV+ OPSCC had higher short-term survival:
• “2-year OS (83.9% vs. 54.9%; p < 0.001)” and “2-year DFS (73.5% vs. 45.6%; p < 0.001)” for HPV+ vs HPV−. (Cleere et al., 2024; https://doi.org/10.1007/s11845-024-03715-4) (cleere2024hpvovertakessmoking pages 1-2)

Prognostic pitfalls of surrogate testing (p16 discordance)

Craig et al. demonstrate clinically important survival divergence: - “p16+/HPV− … five-year survival (33%) compared to p16+ patients (77%)” and similar to p16− (35%). (craig2019recommendationsfordetermining pages 1-2) - Mortality risk under TNM8 downstaging: “mortality rate twice (HR 2.66 [95% CI: 1.37–5.15]) that of p16+/HPV+ patients …” (craig2019recommendationsfordetermining pages 1-2)

Molecularly informed prognosis (integration status)

Tabatabaeian et al. emphasize that fully integrated HPV correlates with “worst clinical outcomes” and limited cytotoxic T-cell infiltration, suggesting integration status is a candidate prognostic and predictive biomarker beyond HPV positivity alone. (tabatabaeian2024navigatingtherapeuticstrategies pages 1-2)

9. Inheritance and Population

Epidemiology and incidence trends (recent quantitative data)

United States (SEER 2010–2017 OPSCC; 2024 analysis) - HPV testing uptake increased from 21.95% (2010) to 51.37% (2014). - HPV positivity among tested OPSCC increased from 66.37% (2010) to 79.32% (2016). - Higher HPV positivity in tonsil and base of tongue vs posterior pharyngeal wall / soft palate. (Kim et al., 2024; https://doi.org/10.1186/s13027-024-00592-5) (kim2024aseerbasedanalysis pages 1-2)

Ireland (Dublin tertiary center, 2012–2021) - HPV+ proportion: 59.5% (175/294). - HPV-linked OPSCC proportion rose from 50.4% (2012–2016) to 65.4% (2017–2021) (p=0.011). (cleere2024hpvovertakessmoking pages 1-2)

Global estimates and regional variation (review synthesis, 2023) - Ndon et al.: “Across the globe, an estimated 30% of oropharyngeal squamous cell carcinomas … are driven by HPV …” (ndon2023humanpapillomavirusassociatedoropharyngeal pages 1-3) - North America ASIR and attributable fraction (as summarized in the paper’s extracted text): “ASIR … 3.41 per 100,000 in males and 0.71 in females … ~63% [attributable fraction].” (ndon2023humanpapillomavirusassociatedoropharyngeal pages 1-3)

Population demographics and disparities (limited by evidence)

Age/sex and policy disparities were discussed at a high level; detailed race/ethnicity-specific incidence or prevalence was not retrieved as primary evidence in this run.

10. Prevention

Primary prevention: HPV vaccination

Ndon et al. emphasize vaccination as primary prevention and highlight policy gaps: - “HPV vaccinations are the primary mode of prevention for HPV-associated OPSCC …” (ndon2023humanpapillomavirusassociatedoropharyngeal pages 10-12) - “As of 2022, 122 of 195 (63%) WHO member states had incorporated HPV vaccinations nationally; of these, 41 of 122 (34%) member states have introduced gender-neutral vaccine coverage.” (ndon2023humanpapillomavirusassociatedoropharyngeal pages 1-3)

They also cite oral infection impact: “Studies have shown that HPV vaccinations have an efficacy of 88–93% against oral HPV infection …” (ndon2023humanpapillomavirusassociatedoropharyngeal pages 1-3)

Real-world implementation gaps (2024 US example)

Adekanmbi et al. (Texas, 2006–2022 vaccination; 2016–2020 cancer IR) show wide geographic variation: - County-level 2021–2022 initiation ranges: 6.3%–69.1% (females) and 7.0%–77.6% (males) ages 9–17. - Up-to-date ranges: 1.6%–30.4% (females) and 2.1%–34.8% (males). - Counties with lower vaccination had higher HPV-related cancer incidence, raising equity concerns. (Published 5 Sep 2024; https://doi.org/10.1001/jamanetworkopen.2024.31807) (adekanmbi2024humanpapillomavirusvaccination pages 1-2)

11. Other Species / Natural Disease

Not addressed in the retrieved evidence corpus.

12. Model Organisms / Experimental Systems

The retrieved evidence set did not include explicit descriptions of animal models or organoid systems for HPV+ OPSCC. This section is therefore not evidence-complete in the current run.

Evidence Synthesis Artifact

The following evidence table consolidates the most directly supported quantitative statements and implementation-relevant facts extracted in this run.

Table: This table compiles concise, evidence-backed facts on HPV-positive head and neck squamous cell carcinoma, with emphasis on HPV-positive OPSCC. It highlights the most actionable findings from the gathered sources across epidemiology, mechanism, diagnostics, prognosis, trials, and prevention.

Expert analysis and key takeaways (evidence-grounded)

1. HPV+ OPSCC is expanding as a public health burden, with increasing HPV positivity proportions in US SEER OPSCC and rising HPV-linked fractions in institutional cohorts. (kim2024aseerbasedanalysis pages 1-2, cleere2024hpvovertakessmoking pages 1-2)
2. Biological heterogeneity matters: HPV integration status may identify a poorer-prognosis subgroup with reduced cytotoxic T infiltration, suggesting that “HPV-positive” is not a sufficient classifier for therapeutic decision-making. (tabatabaeian2024navigatingtherapeuticstrategies pages 1-2)
3. Testing strategy has direct clinical consequences: p16-only classification can mis-stage biologically distinct tumors; p16+/HPV− tumors have survival closer to HPV-negative disease, supporting two-tier HPV testing. (craig2019recommendationsfordetermining pages 1-2, yang2023aptimahrhpvtesting pages 1-2)
4. Immune biology is complex: scRNA-seq supports enhanced interferon/MHC-II programs in HPV+ tumor cells and CXCL13+CD4+ interactions, but checkpoint inhibitor response rates remain ~20%, reinforcing the need for better predictive biomarkers. (yan2024decipheringtheinterplay pages 1-2)
5. De-intensification is being operationalized through risk-stratified surgical pathways (E3311, PATHOS), with co-primary functional outcomes (swallowing) embedded—reflecting a mature shift from purely survival endpoints toward survivorship optimization. (NCT01898494 chunk 1, NCT02215265 chunk 1)

Limitations of this report

Several template elements (ontology IDs, detailed phenotype frequencies, specific host somatic driver gene frequencies, animal models) were not retrievable from the current tool-acquired evidence corpus and are therefore explicitly not fully populated. Where ontology terms were suggested, they are presented as candidate mappings rather than evidence-derived annotations.

References

1. (yan2024decipheringtheinterplay pages 1-2): Shida Yan, Xing Zhang, Qiaohong Lin, Mingyuan Du, Yiqi Li, Shuai He, Jingtao Chen, Xiyuan Li, Jinxin Bei, Shuwei Chen, and Ming Song. Deciphering the interplay of hpv infection, mhc-ii expression, and cxcl13+ cd4+ t cell activation in oropharyngeal cancer: implications for immunotherapy. Cancer Immunology, Immunotherapy : CII, Aug 2024. URL: https://doi.org/10.1007/s00262-024-03789-0, doi:10.1007/s00262-024-03789-0. This article has 11 citations.

2. (ndon2023humanpapillomavirusassociatedoropharyngeal pages 1-3): Sifon Ndon, Amritpal Singh, Patrick K. Ha, Joyce Aswani, Jason Ying-Kuen Chan, and Mary Jue Xu. Human papillomavirus-associated oropharyngeal cancer: global epidemiology and public policy implications. Cancers, 15:4080, Aug 2023. URL: https://doi.org/10.3390/cancers15164080, doi:10.3390/cancers15164080. This article has 58 citations.

3. (craig2019recommendationsfordetermining pages 1-2): Stephanie G. Craig, Lesley A. Anderson, Andrew G. Schache, Michael Moran, Laura Graham, Keith Currie, Keith Rooney, Max Robinson, Navdeep S. Upile, Rachel Brooker, Mina Mesri, Victoria Bingham, Stephen McQuaid, Terry Jones, Dennis J. McCance, Manuel Salto-Tellez, Simon S. McDade, and Jacqueline A. James. Recommendations for determining hpv status in patients with oropharyngeal cancers under tnm8 guidelines: a two-tier approach. British Journal of Cancer, 120:827-833, Mar 2019. URL: https://doi.org/10.1038/s41416-019-0414-9, doi:10.1038/s41416-019-0414-9. This article has 121 citations and is from a domain leading peer-reviewed journal.

4. (kim2024aseerbasedanalysis pages 1-2): Su Il Kim, Jung Woo Lee, Young-Gyu Eun, and Young Chan Lee. A seer-based analysis of trends in hpv-associated oropharyngeal squamous cell carcinoma. Infectious Agents and Cancer, Jun 2024. URL: https://doi.org/10.1186/s13027-024-00592-5, doi:10.1186/s13027-024-00592-5. This article has 12 citations and is from a peer-reviewed journal.

5. (cleere2024hpvovertakessmoking pages 1-2): Eoin F. Cleere, Josh Murphy, Thomas J. Crotty, Justin M. Hintze, Conrad V. I. Timon, John Kinsella, Conall W. R. Fitzgerald, and Paul Lennon. Hpv overtakes smoking as the leading cause of oropharyngeal cancer in ireland: experience of a head and neck surgery tertiary referral centre. Irish Journal of Medical Science, 193:2161-2169, May 2024. URL: https://doi.org/10.1007/s11845-024-03715-4, doi:10.1007/s11845-024-03715-4. This article has 5 citations and is from a peer-reviewed journal.

6. (NCT01898494 chunk 1): Transoral Surgery Followed By Low-Dose or Standard-Dose Radiation Therapy With or Without Chemotherapy in Treating Patients With HPV Positive Stage III-IVA Oropharyngeal Cancer. ECOG-ACRIN Cancer Research Group. 2014. ClinicalTrials.gov Identifier: NCT01898494

7. (NCT02215265 chunk 1): Lisette Nixon. Post-operative Adjuvant Treatment for HPV-positive Tumours (PATHOS). Lisette Nixon. 2015. ClinicalTrials.gov Identifier: NCT02215265

8. (wu2024deescalationstrategiesin pages 1-2): Clinton Wu, Paulina Kuzmin, and Ricklie Julian. De-escalation strategies in hpv-associated oropharynx cancer: a historical perspective with future direction. Cancers, 16:2733, Aug 2024. URL: https://doi.org/10.3390/cancers16152733, doi:10.3390/cancers16152733. This article has 10 citations.

9. (krsek2024thenextchapter pages 1-2): Antea Krsek, Lara Baticic, Tamara Braut, and Vlatka Sotosek. The next chapter in cancer diagnostics: advances in hpv-positive head and neck cancer. Biomolecules, 14:925, Jul 2024. URL: https://doi.org/10.3390/biom14080925, doi:10.3390/biom14080925. This article has 12 citations.

10. (tabatabaeian2024navigatingtherapeuticstrategies pages 1-2): Hossein Tabatabaeian, Yuchen Bai, Ruihong Huang, Akhilanand Chaurasia, and Charbel Darido. Navigating therapeutic strategies: hpv classification in head and neck cancer. British Journal of Cancer, 131:220-230, Apr 2024. URL: https://doi.org/10.1038/s41416-024-02655-1, doi:10.1038/s41416-024-02655-1. This article has 36 citations and is from a domain leading peer-reviewed journal.

11. (atique2024comprehensiveanalysisof pages 55-58): M Atique. Comprehensive analysis of genetic mutations in hpv-positive and hpv-negative oropharyngeal squamous cell carcinoma: a literature review. Unknown journal, 2024.

12. (cleere2024hpvovertakessmoking pages 9-9): Eoin F. Cleere, Josh Murphy, Thomas J. Crotty, Justin M. Hintze, Conrad V. I. Timon, John Kinsella, Conall W. R. Fitzgerald, and Paul Lennon. Hpv overtakes smoking as the leading cause of oropharyngeal cancer in ireland: experience of a head and neck surgery tertiary referral centre. Irish Journal of Medical Science, 193:2161-2169, May 2024. URL: https://doi.org/10.1007/s11845-024-03715-4, doi:10.1007/s11845-024-03715-4. This article has 5 citations and is from a peer-reviewed journal.

13. (yang2023aptimahrhpvtesting pages 1-2): Xin Yang, Chunfang Hu, Huan Zhao, Zhi-hui Zhang, LinLin Zhao, Jing Yu, Xiaoguang Ni, and Huiqin Guo. Aptima hr-hpv testing of cytology specimens is an effective supplement for p16 staining to improve diagnostic accuracy for hpv-related oropharyngeal squamous cell carcinoma. Acta Cytologica, 67:321-332, Dec 2023. URL: https://doi.org/10.1159/000527951, doi:10.1159/000527951. This article has 7 citations and is from a peer-reviewed journal.

14. (ndon2023humanpapillomavirusassociatedoropharyngeal pages 10-12): Sifon Ndon, Amritpal Singh, Patrick K. Ha, Joyce Aswani, Jason Ying-Kuen Chan, and Mary Jue Xu. Human papillomavirus-associated oropharyngeal cancer: global epidemiology and public policy implications. Cancers, 15:4080, Aug 2023. URL: https://doi.org/10.3390/cancers15164080, doi:10.3390/cancers15164080. This article has 58 citations.

15. (adekanmbi2024humanpapillomavirusvaccination pages 1-2): Victor Adekanmbi, Itunu Sokale, Fangjian Guo, Jessica Ngo, Thao N. Hoang, Christine D. Hsu, Abiodun Oluyomi, and Abbey B. Berenson. Human papillomavirus vaccination and human papillomavirus–related cancer rates. JAMA Network Open, 7:e2431807, Sep 2024. URL: https://doi.org/10.1001/jamanetworkopen.2024.31807, doi:10.1001/jamanetworkopen.2024.31807. This article has 13 citations and is from a peer-reviewed journal.