• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.1
• /
• pp.169-174
• /
• 2015

Cervical cancer (CxCa) is the most common cancer in women and a prominent cause of cancer mortality worldwide. The primary cause of CxCa is human papillomavirus (HPV). Radiation therapy and chemotherapy have been used as standard treatments, but they have undesirable side effects for patients. It was reported that gallic acid has antioxidant, antimicrobial, and anticancer activities. Gold nanoparticles are currently being used in medicine as biosensors and drug delivery agents. This study aimed to develop a drug delivery agent using gold nanoparticles conjugated with gallic acid. The study was performed in uninfected (C33A) cervical cancer cells, cervical cancer cells infected with HPV type 16 (CaSki) or 18 (HeLa), and normal Vero kidney cells. The results showed that GA inhibited the proliferation of cancer cells by inducing apoptosis. To enhance the efficacy of this anticancer activity, 15-nm spherical gold nanoparticles (GNPs) were used to deliver GA to cancer cells. The GNPs-GA complex had a reduced ability compared to unmodified GA to inhibit the growth of CxCa cells. It was interesting that high-concentration ($150{\mu}M$) GNPs-GA was not toxic to normal cells, whereas GA alone was cytotoxic. In conclusion, GNPs-GA could inhibit CxCa cell proliferation less efficiently than GA, but it was not cytotoxic to normal cells. Thus, gold nanoparticles have the potential to be used as phytochemical delivery agents for alternative cancer treatment to reduce the side effects of radiotherapy and chemotherapy.

• Journal of Microbiology and Biotechnology
• /
• v.29 no.9
• /
• pp.1444-1452
• /
• 2019

The conventional prophylactic vaccines for human papillomavirus (HPV) efficiently prevent infection with high-risk HPV types, but they do not promote therapeutic effects against cervical cancer. Previously, we developed HPV16 E7-expressing Lactobacillus casei (L. casei-E7) as a therapeutic vaccine candidate for cervical cancer, which induces antitumor therapeutic effects in a TC-1 murine cancer model. To improve the therapeutic effect of L. casei-E7, we performed co-treatment with poly-gamma-glutamic acid (${\gamma}-PGA$), a safe and edible biomaterial naturally secreted by Bacillus subtilis. We investigated their synergistic effect to improve antitumor efficacy in a murine cancer model. The treatment with ${\gamma}-PGA$ did not show in vitro cytotoxicity against TC-1 tumor cells; however, an enhanced innate immune response including activation of dendritic cells was observed. Mice co-administered with ${\gamma}-PGA$ and L. casei-E7 showed significantly suppressed growth of TC-1 tumor cells and an increased survival rate in TC-1 mouse models compared to those of mice vaccinated with L. casei-E7 alone. The administration of ${\gamma}-PGA$ markedly enhanced the activation of natural killer (NK) cells but did not increase the E7-specific cytolytic activity of $CD8^+$ T lymphocytes in mice vaccinated with L. casei-E7. Overall, our results suggest that oral administration of ${\gamma}-PGA$ induces a synergistic antitumor effect in combination with L. casei-E7.

• Journal of Life Science
• /
• v.18 no.12
• /
• pp.1657-1664
• /
• 2008

We determined the prevalence of human papillomavirus (HPV) by DNA chip test in 549 women and cytologic diagnosis. 237 of 549 women (43.17%) subjected with HPV DNA Chip examination were found positive for HPV. 210 (88.60%, High group) were infected with high-risk HPV types. 17 (7.17%, Low group) were infected with low-risk HPV types (6, 11, 40, 44, 70) and 17 (7.17%, Mixed group) were infected with mixed types. According to age, in their twenties, thirties, forties, fifties and over sixties, the prevalence of infection with high-risk HPV types were 1.26% (3/237), 15.61% (37/237), 31.65% (75/237), 23.21% (55/237), and 13.92% (33/237), respectively. In the Low and Mixed group, percentages of infection with HPV were significantly lower than that of the High group. On the comparison of cytologic diagnosis (224 women) by Pap smear and DNA chip positive (237 women) for HPV, 132 out of 194 cases in the High group (68.04%) suffered cervical lesions with ASCUS (atypical squamous cells of undetermined significance, 7.22%), LSIL (low grade squamous intraepithelial lesion, 15.98%), HSIL (high grade SIL, 23.20%) and ICC (invasive cervical cancer, 21.65%). The Low group (14/224 women) showed 1 case of ASCUS and 6 cases of LSIL, whereas the Mixed group (4/224 women) had only 2 cases of ASCUS. According to the HPV subtypes, the high-risk types 16 and 18 induced 26 and 7 cases of ICC, respectively, whereas other HPV subtypes induced lower or no ICC incidence. In conclusion, the present data imply that the prevalence of HPV was 43.17%, high-risk HPV type 16 is a major factor, which causes precancerous and/or cervical cancer in woman and that HPV DNA chip is an accurate and useful tool for detecting HPV.

• Obstetrics & gynecology science
• /
• v.61 no.6
• /
• pp.662-668
• /
• 2018

Objective This study was to identify the risk factors for cytological progression in women with atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL). Methods We analyzed data from women infected with the human papillomavirus (HPV) who participated in the Korean HPV cohort study. The cohort recruited women aged 20-60 years with abnormal cervical cytology (ASC-US or LSIL) from April 2010. All women were followed-up at every 6-month intervals with cervical cytology and HPV DNA testing. Results Of the 1,158 women included, 654 (56.5%) and 504 (43.5%) women showed ASC-US and LSIL, respectively. At the time of enrollment, 143 women tested positive for HPV 16 (85 single and 58 multiple infections). Cervical cytology performed in the HPV 16-positive women showed progression in 27%, no change in 23%, and regression in 50% of the women at the six-month follow-up. The progression rate associated with HPV 16 infection was higher than that with infection caused by other HPV types (relative risk [RR], 1.75; 95% confidence interval [CI], 1.08-2.84; P=0.028). The cytological progression rate in women with persistent HPV 16 infection was higher than that in women with incidental or cleared infections (P<0.001). Logistic regression analysis showed a significant relationship between cigarette smoking and cytological progression (RR, 4.15; 95% CI, 1.01-17.00). Conclusion The cytological progression rate in HPV 16-positive women with ASC-US or LSIL is higher than that in women infected with other HPV types. Additionally, cigarette smoking may play a role in cytological progression.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.23
• /
• pp.10061-10066
• /
• 2015

Background: The aetiological relationship between human papillomavirus (HPV) infection and cervical cancer (CC) is widely accepted. Our goal was to determine the prevalence of HPV types in Mexican women attending at the Mexican Institute for Social Security from different areas of Mexico. Materials and Methods: DNAs from 2,956 cervical samples were subjected to HPV genotyping: 1,020 samples with normal cytology, 931 with low-grade squamous intraepithelial lesions (LGSIL), 481 with high grade HGSIL and 524 CC. Results: Overall HPV prevalence was 67.1%. A total of 40 HPV types were found; HPV16 was detected in 39.4% of the HPV-positive samples followed by HPV18 at 7.5%, HPV31 at 7.1%, HPV59 at 4.9%, and HPV58 at 3.2%. HPV16 presented the highest prevalence both in women with altered or normal cytology and HPV 18 presented a minor prevalence as reported worldwide. The prevalence ratio (PR) was calculated for the HPV types. The analysis of PR showed that HPV16 presents the highest association with CC, HPV 31, -33, -45, -52 and -58 also demonstrating a high association. Conclusions: The most prevalent HPV types in cervical cancer samples were -16, -18, -31, but it is important to note that we obtained a minor prevalence of HPV18 as reported worldwide, and that HPV58 and -52 also were genotypes with an important prevalence in CC samples. Determination of HPV genotypes is very important in order to evaluate the impact of vaccine introduction and future cervical cancer prevention strategies.

• Korean Journal of Head & Neck Oncology
• /
• v.33 no.2
• /
• pp.9-15
• /
• 2017

The recently released the $8^{th}$ edition of the American Joint Committee on Cancer (AJCC) Staging Manual introduces significant modifications from the prior $7^{th}$ edition. In this paper, the contents of the new changes in the decision of cancer of the head and neck is summarized except changes in staging of skin and thyroid cancer. In addition to the 8th edition, 1) Addition of extracapsular involvement in metastatic lymph nodes (N category) 2) Oral cancer T classification change, 3) Staging of the pharyngeal cancer was divided into 3 chapters: high-risk human papilloma virus (HR-HPV) associated oropharyngeal cancer (OPC), non HR-HPV associated OPC and hypopharynx cancer (HPC), and nasopharynx cancer (NPC) 4) Changes in T and N classification in NPC, 5) In the case of cancer of unknown primary, P16-positive case is defined as HR-HPV related OPC, and EBV-positive case is defined as NPC. The process that led to these changes highlights the need to collect high-fidelity cancer registry-level data that can be used to confirm prognostic observations identified in institutional data sets. Clinicians will continue to use the latest information for patient care, including scientific content of the 8th Edition Manual. All newly diagnosed cases through December $31^{st}$ 2017 should be staged with the 7th edition. The time extension will allow all partners to develop and update protocols and guidelines and for software vendors to develop, test, and deploy their products in time for the data collection and implementation of the 8th edition in 2018. The 8th edition strikes a balance between a personalized, complex system and a more general, simpler one that maintains the user-friendliness and worldwide acceptability of the traditional TNM staging paradigm.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.1
• /
• pp.503-506
• /
• 2013

Objectives: To determine human papillomavirus (HPV) frequency, genotypes and the relation between cervical smear results, risk factors and types in women living in Manisa, Turkey. Materials and Methods: A total of 410 women were included in the study. Cervical specimens were obtained for linear array HPV genotyping and pathological testing. Conventional Pap test and Bethesda system were used for evaluation of cytology specimens. Results: A total of 410 women with a mean age of 34.9 years were tested. A positive result of any HPV was found in 35 patients (8.5%). Among them, 26 different serotypes of HPV were identified and the most frequent type was HPV 16 (28.5%) followed by type 45 and 53 (11.4%). Patients were infected by 65.7% high risk, 11.4% probable high risk and 22.9% low risk HPV types. Multiple HPV positive results were found in 13 patients (37.1%). Patients with single partner, history of abnormal smear or condyloma had positive HPV results and this was statistically significant (p<0.05). Correlation analysis showed a statistically weak relation between positive HPV and abnormal smear results (r=0.120). Conclusions: Determining HPV types of genital HPV infections is important for epidemiological studies. We have found the rate of positive HPV as 8.5% which implies the need for extended screening programs in order to diagnose oncogenic HPV at an early stage.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.12
• /
• pp.6109-6113
• /
• 2012

Background: Oral cancer has become one of the most prevalent cancers worldwide and human Papillomavirus is one of the risk factors for developing oral cancer. For this study HPV18 was chosen as it is one of the high risk HPV types and may lead to carcinogenesis. However, prevalence of HPV18 infection in Oral Squamous Cell Carcinoma in Malaysia remains unclear. Objective: This study aimed to investigate the viral load of HPV18 DNA in OSCC and potentially malignant lesions using saliva samples. Materials and Methods: Genomic DNAs of thirty saliva samples of normal subjects and thirty saliva samples compromised of 16 samples from potentially malignant lesions and 14 of OSCC patients were amplified for HPV18 DNA using a nested polymerase chain reaction analysis. All PCR products were then analyzed using the Bioanalyzer to confirm presence of HPV18 DNA. Result: From thirty patients examined, only one of 30 (3.3%) cases was found to be positive for HPV18 in this study. Conclusion: The finding of this study revealed that there is a low viral detection of HPV18 in Malaysian OSCC by using saliva samples, suggesting that prevalence of HPV18 may not be important in this group of Malaysian OSCC.

• Korean Journal of Head & Neck Oncology
• /
• v.27 no.1
• /
• pp.17-21
• /
• 2011

연구 및 목적 : 이번 연구의 목적은 한국인에서 편도 편평세포암종의 발생에 고위험 인간유두종 바이러스(high risk human pap-illomavirus)의 역할 및 관여 인자에 대해 밝히고자 한다. 재료 및 방법 : 연구는 편도 편평상피세포암종으로 진단받은 54명을 대상으로 하였다. 고위험 인간유두종 바이러스의 감염을 알기위해 in situ hybridization 방법을 이용하였다. 고위험 인간유두종 바이러스의 감염과 나이, 성별, 흡연, 음주, 병기, 병리학적 특징 등과의 관계를 분석하였다. 결 과 : 고위험 인간유두종 바이러스의 양성율은 31.5%(17/54)였다. 고위험 인간유두종 바이러스 감염은 젊은 연령(50세 미만), 비흡연자, 림프절 전이와 유의한 상관관계가 있었다(각각 p=0.008, p=0.042, p=0.027). 하지만 성별, 음주, 원발부위 병기, 종양분화도, 피막외침범, 혈관 및 신경 침범과 고위험 인간유두종 바이러스와의 관계는 통계적으로 유의하지 않았다. 6개월 이상 추적 관찰이 가능한 환자를 대상으로 조사한 5년 전체 생존율 및 질병 특이 생존율은 각각 60%와 62%였다. 고위험 인간유두종 바이러스의 양성율은 질병 특이 생존율과 유의한 상관관계가 있었다(p=0.019). 결 론 : 한국인의 고위험 인간유두종 바이러스 감염은 젊은 연령 및 비흡연자의 편도 편평세포암종의 발생에 관련이 있고 예후 인자로 중요한 역할을 한다.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.18
• /
• pp.8495-8501
• /
• 2016

Purpose: This study was conducted to assess the agreement and differences between cervical self-sampling with a Kato device (KSSD) and gynecologist sampling for Pap cytology and human papillomavirus DNA (HPV DNA) detection. Materials and Methods: Women underwent self-sampling followed by gynecologist sampling during screening at two primary health clinics. Pap cytology of cervical specimens was evaluated for specimen adequacy, presence of endocervical cells or transformation zone cells and cytological interpretation for cells abnormalities. Cervical specimens were also extracted and tested for HPV DNA detection. Positive HPV smears underwent gene sequencing and HPV genotyping by referring to the online NCBI gene bank. Results were compared between samplings by Kappa agreement and McNemar test. Results: For Pap specimen adequacy, KSSD showed 100% agreement with gynecologist sampling but had only 32.3% agreement for presence of endocervical cells. Both sampling showed 100% agreement with only 1 case detected HSIL favouring CIN2 for cytology result. HPV DNA detection showed 86.2%agreement (K=0.64, 95% CI 0.524-0.756, p=0.001) between samplings. KSSD and gynaecologist sampling identified high risk HPV in 17.3% and 23.9% respectively (p=0.014). Conclusion: The self-sampling using Kato device can serve as a tool in Pap cytology and HPV DNA detection in low resource settings in Malaysia. Self-sampling devices such as KSSD can be used as an alternative technique to gynaecologist sampling for cervical cancer screening among rural populations in Malaysia.