The Effect of HPV DNA and P16 Status on the Prognosis of Patients with Hypopharyngeal Carcinoma: a Meta-analysis

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2022 Jun 15

PMID 35705893

Authors

Jinfeng Shi

Ling Wang

Nan Yao

Le Sun

Wenyu Hu

Xiaotong Li

Yixue Yang

Yusheng Wang

Wei Zhu

Bo Li

Affiliations

Soon will be listed here.

Abstract

Objective: To evaluate whether the presence of human papillomavirus (HPV) DNA and p16 might be associated with better prognosis in patients with hypopharyngeal carcinoma (HPC), especially on overall survival (OS) and disease-free survival (DFS).

Method: PubMed, the Cochrane Library, the Web of Science and EMBASE were searched from inception to April 2021 to search for HPV DNA- and p16-related prognostic articles on HPC. Meta-analysis was performed on the selected articles according to the inclusion and exclusion criteria. Publication bias was assessed for the included studies with Egger's test. All studies were analyzed by using Stata 16.0 statistical software.

Results: A total of 18 studies were included, including 12 HPV DNA studies and 11 p16 studies. Meta-analysis showed that HPV DNA positivity was a strong prognostic factor for improved OS in patients with HPC, with a pooled hazard ratio (HR) of 0.61 (95% CI, 0.54-0.69), but there was no statistically significant difference in DFS (HR, 0.60; 95% CI, 0.31-1.16). Patients with p16-positive tumors had better OS (HR, 0.66; 95% CI, 0.49-0.89) and DFS (HR, 0.59; 95% CI, 0.44-0.78) than patients with p16-negative tumors.

Conclusions: This study suggests that the presence of HPV DNA leads to better OS in patients with HPC, and the presence of p16 also corresponds to better OS and DFS. Our results provide up-to-date evidence to clinicians and researchers. Larger studies adjusting for prognostic factors are needed in subsequent studies.

Citing Articles

Roles of human papillomavirus in cancers: oncogenic mechanisms and clinical use.

Zhang Y, Qiu K, Ren J, Zhao Y, Cheng P Signal Transduct Target Ther. 2025; 10(1):44.

PMID: 39856040 PMC: 11760352. DOI: 10.1038/s41392-024-02083-w.

The effect of circulating tumor DNA on the prognosis of patients with head and neck squamous cell carcinoma: a systematic review and meta-analysis.

Yang R, Li T, Zhang S, Shui C, Ma H, Li C BMC Cancer. 2024; 24(1):1434.

PMID: 39574043 PMC: 11580464. DOI: 10.1186/s12885-024-13116-6.

Influencing Factors of Survival in Hypopharyngeal Squamous Cell Cancer.

Repassy G, Hargas D, Molnar A, Maihoub S, Tamas L J Clin Med. 2024; 13(13).

PMID: 38999419 PMC: 11242062. DOI: 10.3390/jcm13133853.

The Role of the p16 and p53 Tumor Suppressor Proteins and Viral HPV16 E6 and E7 Oncoproteins in the Assessment of Survival in Patients with Head and Neck Cancers Associated with Human Papillomavirus Infections.

Lifsics A, cistjakovs M, Sokolovska L, Deksnis R, Murovska M, Groma V Cancers (Basel). 2023; 15(10).

PMID: 37345059 PMC: 10216029. DOI: 10.3390/cancers15102722.

The complexity of human papilloma virus in cancers: a narrative review.

Hamidi Sofiani V, Veisi P, Rezaei Zadeh Rukerd M, Ghazi R, Nakhaie M Infect Agent Cancer. 2023; 18(1):13.

PMID: 36843070 PMC: 9969657. DOI: 10.1186/s13027-023-00488-w.

References

Gissmann L, Wolnik L, Ikenberg H, Koldovsky U, Schnurch H, zur Hausen H . Human papillomavirus types 6 and 11 DNA sequences in genital and laryngeal papillomas and in some cervical cancers. Proc Natl Acad Sci U S A. 1983; 80(2):560-3. PMC: 393419. DOI: 10.1073/pnas.80.2.560. View

Tierney J, Stewart L, Ghersi D, Burdett S, Sydes M . Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007; 8:16. PMC: 1920534. DOI: 10.1186/1745-6215-8-16. View

Rodrigo J, Hermsen M, Fresno M, Brakenhoff R, Garcia-Velasco F, Snijders P . Prevalence of human papillomavirus in laryngeal and hypopharyngeal squamous cell carcinomas in northern Spain. Cancer Epidemiol. 2014; 39(1):37-41. DOI: 10.1016/j.canep.2014.11.003. View

Tian S, Switchenko J, Jhaveri J, Cassidy R, Ferris M, Press R . Survival outcomes by high-risk human papillomavirus status in nonoropharyngeal head and neck squamous cell carcinomas: A propensity-scored analysis of the National Cancer Data Base. Cancer. 2019; 125(16):2782-2793. PMC: 6663628. DOI: 10.1002/cncr.32115. View

Meshman J, Wang P, Chin R, St John M, Abemayor E, Bhuta S . Prognostic significance of p16 in squamous cell carcinoma of the larynx and hypopharynx. Am J Otolaryngol. 2016; 38(1):31-37. DOI: 10.1016/j.amjoto.2016.09.007. View

Burbure N, Handorf E, Ridge J, Bauman J, Liu J, Giri A . Prognostic significance of human papillomavirus status and treatment modality in hypopharyngeal cancer. Head Neck. 2021; 43(10):3042-3052. PMC: 9631108. DOI: 10.1002/hed.26793. View

Fakhry C, Westra W, Li S, Cmelak A, Ridge J, Pinto H . Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008; 100(4):261-9. DOI: 10.1093/jnci/djn011. View

Wilson D, Rahimi A, Saylor D, Stelow E, Jameson M, Shonka D . p16 not a prognostic marker for hypopharyngeal squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 2012; 138(6):556-61. DOI: 10.1001/archoto.2012.950. View

Weeramange C, Liu Z, Hartel G, Li Y, Vasani S, Langton-Lockton J . Salivary High-Risk Human Papillomavirus (HPV) DNA as a Biomarker for HPV-Driven Head and Neck Cancers. J Mol Diagn. 2021; 23(10):1334-1342. PMC: 9344924. DOI: 10.1016/j.jmoldx.2021.07.005. View

10.

Urbute A, Rasmussen C, Belmonte F, Obermueller T, Prigge E, Arbyn M . Prognostic Significance of HPV DNA and p16 in Anal Cancer: A Systematic Review and Meta-Analysis. Cancer Epidemiol Biomarkers Prev. 2020; 29(4):703-710. DOI: 10.1158/1055-9965.EPI-19-1259. View

11.

Cai C, Chernock R, Pittman M, El-Mofty S, Thorstad W, Lewis Jr J . Keratinizing-type squamous cell carcinoma of the oropharynx: p16 overexpression is associated with positive high-risk HPV status and improved survival. Am J Surg Pathol. 2014; 38(6):809-15. DOI: 10.1097/PAS.0000000000000183. View

12.

Dalianis T, Grun N, Koch J, Vlastos A, Tertipis N, Nordfors C . Human papillomavirus DNA and p16(INK4a) expression in hypopharyngeal cancer and in relation to clinical outcome, in Stockholm, Sweden. Oral Oncol. 2015; 51(9):857-61. DOI: 10.1016/j.oraloncology.2015.06.002. View

13.

Lassen P, Primdahl H, Johansen J, Kristensen C, Andersen E, Andersen L . Impact of HPV-associated p16-expression on radiotherapy outcome in advanced oropharynx and non-oropharynx cancer. Radiother Oncol. 2014; 113(3):310-6. DOI: 10.1016/j.radonc.2014.11.032. View

14.

Wendt M, Romanitan M, Nasman A, Dalianis T, Hammarstedt L, Marklund L . Presence of human papillomaviruses and p16 expression in hypopharyngeal cancer. Head Neck. 2013; 36(1):107-12. DOI: 10.1002/hed.23394. View

15.

Abdel-Rahman O . Prognostic value of HPV status among patients with hypopharyngeal carcinoma: a population-based study. Clin Transl Oncol. 2020; 22(9):1645-1650. DOI: 10.1007/s12094-020-02289-8. View

16.

Mirghani H, Amen F, Tao Y, Deutsch E, Levy A . Increased radiosensitivity of HPV-positive head and neck cancers: Molecular basis and therapeutic perspectives. Cancer Treat Rev. 2015; 41(10):844-52. DOI: 10.1016/j.ctrv.2015.10.001. View

17.

Konig F, Krekeler G, Honig J, Cordon-Cardo C, Fischer G, Korabiowska M . Relation between human papillomavirus positivity and p16 expression in head and neck carcinomas--a tissue microarray study. Anticancer Res. 2007; 27(1A):283-8. View

18.

Bates J, Morris C, Hitchcock K, Dziegielewski P, Mendenhall W, Amdur R . Locally advanced hypopharyngeal and laryngeal cancer: Influence of HPV status. Radiother Oncol. 2019; 140:6-9. DOI: 10.1016/j.radonc.2019.05.013. View

19.

Jakobsen K, Wingstrand V, Jensen J, Gronhoj C, Jensen D, Karnov K . Incidence and survival of hypopharyngeal cancer: a Danish Nation-Wide Study from 1980 to 2014. Acta Oncol. 2019; 58(11):1570-1576. DOI: 10.1080/0284186X.2019.1657585. View

20.

Lewis Jr J, Thorstad W, Chernock R, Haughey B, Yip J, Zhang Q . p16 positive oropharyngeal squamous cell carcinoma:an entity with a favorable prognosis regardless of tumor HPV status. Am J Surg Pathol. 2010; 34(8):1088-96. PMC: 3873742. DOI: 10.1097/PAS.0b013e3181e84652. View