Human Papillomavirus Association and Genomic Exploration in Head-Neck Squamous Cell Carcinomas (HPV & HNSCC)

Exploration of Human Papillomavirus Association and Genomic Characteristics in Head and Neck Squamous Cell Carcinomas in Bangladesh

Head and neck squamous cell carcinoma (HNSCC) represents a significant public health burden in Bangladesh with a high incidence and mortality rate. While traditional risk factors like tobacco and betel nut chewing contribute to HNSCC incidence, the emergence of HPV-associated HNSCC presents a unique challenge. The main goal of this observational study is to explore the prevalence, risk factors, and biological mechanisms underlying food habits and HPV-driven HNSCC in the population and identify the genomic changes and characteristics related to this malignancy. This study will provide the prevalence of HPV-associated HNSCC and screening the HPV typing in the Bangladeshi population, identify risk factors, and any biologically driven mechanisms causing HNSCC.

Study Overview

• Status: Recruiting
• Conditions: Oropharyngeal Neoplasms; Head Neck Cancer
• Intervention / Treatment: Diagnostic test: Histopathology, Immunohistochemistry, Real-Time PCR, Sequencing

Detailed Description

Head and neck squamous cell carcinoma (HNSCC) represents Bangladesh's significant public health challenge. According to GLOBACAN data, these cancers are among the most prevalent malignancies in the country, with a considerable impact on morbidity and mortality rates. Several factors contribute to the high incidence of HNSCC in Bangladesh, including prevalent tobacco and betel nut chewing habits, poor oral hygiene practices, oncogenic viruses such as human papillomavirus (HPV), and limited access to healthcare facilities for early detection and treatment. In recent years, the incidence of HPV-associated HNSCC has been on the rise, posing a significant health concern globally. HPV16 and HPV18 have been strongly linked to the development of HNSCC. The global surge of HPV-associated HNSCC necessitates further investigation, particularly in regions like Bangladesh. By addressing these critical areas, this research has the potential to improve public health outcomes in Bangladesh significantly.

The main goal of this observational study is to explore the prevalence, risk factors, and biological mechanisms underlying food habits and HPV-driven HNSCC in the Bangladeshi population. Additionally, the study aims to identify the gene expression changes related to these factors.

At first, the HNSCC samples will be detected through histopathology analysis, followed by nucleic acid extraction from the carcinoma-positive samples. Subsequently, molecular screening will be conducted alongside an assessment of patient histories. Based on the results from the molecular screening, immunohistochemistry will be performed on both HPV-positive and HPV-negative HNSCC samples to assess carcinoma-related protein expression. Finally, a comprehensive cancer omics analysis will be conducted after obtaining the sequencing data. Understanding these aspects is crucial for developing targeted prevention strategies, including HPV vaccination campaigns and public health education initiatives on high-risk sexual behavior.

• Study Type: Observational
• Enrollment (Estimated): 550

Contacts and Locations

• Study Contact: Name: Syed Farhan Ali Razib, FCPS; Phone Number: +8801714043556; Email: razib10@bsmmu.edu.bd
• Study Contact Backup: Name: S M Rashed Ul Islam, M. Phil, MPH; Phone Number: +8801713236399; Email: smrashed@bsmmu.edu.bd

Study Locations

• Bangladesh
  • Dhaka, Bangladesh, 1000
    • Recruiting
    • Bangabandhu Sheikh Mujib Medical University (BSMMU)
    • Contact: Syed Farhan Ali Razib, FCPS; Phone Number: +8801714043556; Email: razib10@bsmmu.edu.bd
    • Contact: S M Rashed Ul Islam, M. Phil, MPH; Phone Number: +8801713236399; Email: smrashed@bsmmu.edu.bd
    • Contact: Syed Farhan Ali Razib, FCPS
    • Contact: Bishnu Pada Dey, MD
    • Contact: Afzalun Nessa, M. Phil

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

A descriptive study will be conducted among head-neck squamous cell carcinoma people, who will be recruited after receiving informed written consent to participate. The study population will be recruited from the Department of Otolaryngology-Head & Neck Surgery, histopathology of the BSMMU, and laboratory work will be done at the Department of Virology, BSMMU. During the specimen collection, brief demographic and clinical data will be collected through a pre-designed written questionnaire.

Description

Inclusion Criteria:

1. Patient Age: adult (> 18 years)
2. Head and neck squamous cell carcinoma diagnosed by biopsy (Histopathology confirmed HNSCC).
3. Diagnosed cases specific Head-Neck sub-sites: (oral cavity, oropharynx, hypopharynx, larynx, tongue)
4. Patient's Consent

Exclusion Criteria:

1. Patient Age: children (< 18 years)
2. Cancers of any part of the body other than the head-neck region.
3. People without HNSCC
4. Any chronic diseases, genetic diseases, acute/chronic infectious diseases, etc. -

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HPV Positive HNSCC Population; Tissues from Head Neck Squamous Cell Carcinoma and HPV DNA-positive	Diagnostic test: Histopathology, Immunohistochemistry, Real-Time PCR, Sequencing; Histopathology for carcinoma detection, Immunohistochemistry for carcinoma-related protein expression, Real-Time PCR for HPV association and HPV typing, Sequencing for genetic study or mutation analysis.
HPV Negative HNSCC Population; Tissues from Head Neck Squamous Cell Carcinoma and HPV DNA-negative	Diagnostic test: Histopathology, Immunohistochemistry, Real-Time PCR, Sequencing; Histopathology for carcinoma detection, Immunohistochemistry for carcinoma-related protein expression, Real-Time PCR for HPV association and HPV typing, Sequencing for genetic study or mutation analysis.
Healthy Population; Healthy Population who does not have any carcinoma, chronic diseases, Genetic diseases, acute/chronic infectious diseases, etc.	Diagnostic test: Histopathology, Immunohistochemistry, Real-Time PCR, Sequencing; Histopathology for carcinoma detection, Immunohistochemistry for carcinoma-related protein expression, Real-Time PCR for HPV association and HPV typing, Sequencing for genetic study or mutation analysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HPV positivity in histopathological positive HNSCC detected tissue samples	To detect and type the HPV DNA in HNSCC tissue samples utilizing Real-Time PCR and Histopathology.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic predisposition to HNSCC due to virus, Food habit or Tobacco	To explore any influence of HPV positivity and food habits, like betel nut, betel leaf, tobacco, alcohol, etc, through genetic analysis.	2 years

Collaborators and Investigators

• Sponsor: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
• Investigators: Principal Investigator: S M Rashed Ul Islam, M. Phil, MPH, Bangabandhu Sheikh Mujib Medical University (BSMMU)

Publications and helpful links

General Publications

• Akhter M, Ali L, Hassan Z, Khan I. Association of human papilloma virus infection and oral squamous cell carcinoma in Bangladesh. J Health Popul Nutr. 2013 Mar;31(1):65-9. doi: 10.3329/jhpn.v31i1.14750.
• Gao G, Wang J, Kasperbauer JL, Tombers NM, Teng F, Gou H, Zhao Y, Bao Z, Smith DI. Whole genome sequencing reveals complexity in both HPV sequences present and HPV integrations in HPV-positive oropharyngeal squamous cell carcinomas. BMC Cancer. 2019 Apr 11;19(1):352. doi: 10.1186/s12885-019-5536-1.
• Lechner M, Frampton GM, Fenton T, Feber A, Palmer G, Jay A, Pillay N, Forster M, Cronin MT, Lipson D, Miller VA, Brennan TA, Henderson S, Vaz F, O'Flynn P, Kalavrezos N, Yelensky R, Beck S, Stephens PJ, Boshoff C. Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors. Genome Med. 2013 May 29;5(5):49. doi: 10.1186/gm453. eCollection 2013.
• Shaikh MH, Khan AI, Sadat A, Chowdhury AH, Jinnah SA, Gopalan V, Lam AK, Clarke DTW, McMillan NAJ, Johnson NW. Prevalence and types of high-risk human papillomaviruses in head and neck cancers from Bangladesh. BMC Cancer. 2017 Nov 25;17(1):792. doi: 10.1186/s12885-017-3789-0.

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2024
• Primary Completion (Estimated): March 30, 2025
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: October 12, 2024
• First Submitted That Met QC Criteria: October 12, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 28, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Neoplasms, Squamous Cell; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Oropharyngeal Neoplasms
• Other Study ID Numbers: BSMMU HNSCC Study-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: BSMMU supports the International Committee of Medical Journal Editors (ICMJE) and the ethical obligation of responsible sharing of data from this study.
• IPD Sharing Time Frame: 12 months after publication and for up to 36 months post-publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes