TY - BOOK
T1 - Biomarkers in HPV-related and HPV-unrelated oropharyngeal squamous cell carcinoma : novel tools to enhance survival assessment and treatment solutions
AU - Sjöblom, Anni
N1 - M1 - 94 s. + liitteet
PY - 2024
Y1 - 2024
N2 - Regarded as one of the ten most common cancer types in the world, Head and Neck cancers (HNCs) are usually complex, and disease management often requires a multidisciplinary approach. Oropharyngeal squamous cell carcinoma (OPSCC) is a subtype of HNCs, and two separate subtypes of OPSCC are further known today: human papillomavirus (HPV)-related OPSCC and HPV-unrelated OPSCC, the disease profiles and survival of which differ remarkably. The incidence of HPV-related OPSCC is rising rapidly in Western countries specifically. However, despite the favorable treatment outcomes among HPV-positive patients, unfortunately the prognosis for HPV-unrelated OPSCC remains poor. Novel diagnostic methods and treatment modalities are warranted, and utilizing cancer biomarkers with OPSCC patients could provide numerous benefits in disease management. Monitoring biomarkers has previously been proven valuable for other malignancies, of which the screening of prostate-specific antigen (PSA) for prostate cancer serves as a valuable example. Other benefits of biomarkers include relatively low costs, accessibility, repeatability, and minimal invasiveness. To further facilitate the management of OPSCC, biomarker assays could assist in the development of individualized and targeted treatment modalities. However, introducing novel biomarkers into the clinic can be challenging, requiring careful research to achieve advancements. Our aim was to observe novel tissue and serum specific biomarkers in OPSCC among HPV-positive and HPV-negative patients, and to tentatively assess their potential benefits and prognostic value in clinical use. We selected biomarkers based on their previously identified associations with other malignancies, such as other cancers of the head and neck region. To obtain information about the biomarker functions in the OPSCC disease profile, we compared the biomarker assays to OPSCC patient data containing information on clinical characteristics and survival. The patient material consisted of 224 OPSCC patients treated at the Helsinki University Hospital (HUS, Helsinki, Finland) during 2012 – 2016. An additional cohort (n = 192) was used in Study V, comprising OPSCC patients treated at the HUS during 2000 – 2009. Details on clinical characteristics and survival data were collected manually from the hospital electronic patient records at HUS. HPV status for these studies was determined by p16 immunohistochemistry, HPV DNA genotyping and HPV mRNA in situ hybridization.Immunofluorometric assays were performed to assess biomarker levels in serum and immunohistochemical analyses were utilized to observe biomarker immunopositivity in cancer tissues. Statistical analyses were performed with IBM SPSS software. The biomarkers observed in our study were tumor-associated trypsin inhibitor (TATI), human chorionic gonadotropin β-subunit (hCGβ), liprin-α1, CD82, and immunoglobulin superfamily member 3 (IGSF3). Several differences in the clinicopathological profiles of HPV-related and HPV-unrelated OPSCC were found (Study I). TATI serum positivity correlated with poor prognosis in OPSCC irrespective of HPV status and TATI serum negativity was associated with HPV-positivity (Study II). Serum positivity of hCGβ additionally correlated with poor prognosis in OPSCC (Study III). In separate analyses, strong tissue immunopositivity of liprin-α1 and IGSF3 in tumor cells correlated with poor prognosis, whereas immunopositivity in tumor-infiltrating lymphocytes correlated with favorable prognosis (Studies IV – V). Several biomarkers were found to have prognostic potential. Further biomarker studies concerning OPSCC are warranted and incorporating analyses within subgroups according to HPV status is highly recommended.
AB - Regarded as one of the ten most common cancer types in the world, Head and Neck cancers (HNCs) are usually complex, and disease management often requires a multidisciplinary approach. Oropharyngeal squamous cell carcinoma (OPSCC) is a subtype of HNCs, and two separate subtypes of OPSCC are further known today: human papillomavirus (HPV)-related OPSCC and HPV-unrelated OPSCC, the disease profiles and survival of which differ remarkably. The incidence of HPV-related OPSCC is rising rapidly in Western countries specifically. However, despite the favorable treatment outcomes among HPV-positive patients, unfortunately the prognosis for HPV-unrelated OPSCC remains poor. Novel diagnostic methods and treatment modalities are warranted, and utilizing cancer biomarkers with OPSCC patients could provide numerous benefits in disease management. Monitoring biomarkers has previously been proven valuable for other malignancies, of which the screening of prostate-specific antigen (PSA) for prostate cancer serves as a valuable example. Other benefits of biomarkers include relatively low costs, accessibility, repeatability, and minimal invasiveness. To further facilitate the management of OPSCC, biomarker assays could assist in the development of individualized and targeted treatment modalities. However, introducing novel biomarkers into the clinic can be challenging, requiring careful research to achieve advancements. Our aim was to observe novel tissue and serum specific biomarkers in OPSCC among HPV-positive and HPV-negative patients, and to tentatively assess their potential benefits and prognostic value in clinical use. We selected biomarkers based on their previously identified associations with other malignancies, such as other cancers of the head and neck region. To obtain information about the biomarker functions in the OPSCC disease profile, we compared the biomarker assays to OPSCC patient data containing information on clinical characteristics and survival. The patient material consisted of 224 OPSCC patients treated at the Helsinki University Hospital (HUS, Helsinki, Finland) during 2012 – 2016. An additional cohort (n = 192) was used in Study V, comprising OPSCC patients treated at the HUS during 2000 – 2009. Details on clinical characteristics and survival data were collected manually from the hospital electronic patient records at HUS. HPV status for these studies was determined by p16 immunohistochemistry, HPV DNA genotyping and HPV mRNA in situ hybridization.Immunofluorometric assays were performed to assess biomarker levels in serum and immunohistochemical analyses were utilized to observe biomarker immunopositivity in cancer tissues. Statistical analyses were performed with IBM SPSS software. The biomarkers observed in our study were tumor-associated trypsin inhibitor (TATI), human chorionic gonadotropin β-subunit (hCGβ), liprin-α1, CD82, and immunoglobulin superfamily member 3 (IGSF3). Several differences in the clinicopathological profiles of HPV-related and HPV-unrelated OPSCC were found (Study I). TATI serum positivity correlated with poor prognosis in OPSCC irrespective of HPV status and TATI serum negativity was associated with HPV-positivity (Study II). Serum positivity of hCGβ additionally correlated with poor prognosis in OPSCC (Study III). In separate analyses, strong tissue immunopositivity of liprin-α1 and IGSF3 in tumor cells correlated with poor prognosis, whereas immunopositivity in tumor-infiltrating lymphocytes correlated with favorable prognosis (Studies IV – V). Several biomarkers were found to have prognostic potential. Further biomarker studies concerning OPSCC are warranted and incorporating analyses within subgroups according to HPV status is highly recommended.
KW - Oropharyngeal Neoplasms
KW - +diagnosis
KW - +immunology
KW - +mortality
KW - +therapy
KW - +virology
KW - Squamous Cell Carcinoma of Head and Neck
KW - Biomarkers, Tumor
KW - Risk Assessment
KW - Survival Rate
KW - Papillomavirus Infections
KW - Trypsin Inhibitor, Kazal Pancreatic
KW - Chorionic Gonadotropin, beta Subunit, Human
KW - Adaptor Proteins, Signal Transducing
KW - Kangai-1 Protein
KW - Immunoglobulins
KW - Membrane Proteins
KW - Tumor Microenvironment
KW - 3111 Biomedicine
KW - 3125 Otorhinolaryngology, ophthalmology
KW - 3122 Cancers
M3 - Doctoral Thesis
SN - 978-951-51-9574-6
T3 - Dissertationes Universitatis Helsingiensis
PB - Helsingin yliopisto
CY - Helsinki
ER -