Human papillomavirus (HPV) is a major causative agent of head and neck squamous cell carcinomas (HNSCC). Over the past several decades, an increasing number of studies established the strong association of HPV with the invasion and metastasis of HNSCC. In the present study, we reviewed the gene mutations in HPV-associated HNSCC and the unique mechanism of E6- and E7-mediated carcinogenesis via interactions with an array of cellular elements. We further discussed the progress in the mechanisms of invasion and metastasis; these mechanisms include non-coding RNAs, deregulating cellular energetics, tumor microenvironment, cancer stem cells, angiogenesis, and lymphangiogenesis.
Head and Neck Neoplasms ; pathology ; virology ; Humans ; Neoplasm Invasiveness ; Neoplasm Metastasis ; Papillomaviridae ; Papillomavirus Infections ; Squamous Cell Carcinoma of Head and Neck ; pathology ; virology

OBJECTIVE: DNA methylation has been shown to be a potential biomarker for early cancer detection. The aim of this study was to evaluate DNA methylation profiles according to liquid-based Pap (LBP) test results and to assess their diagnostic value in a Korean population. METHODS: A total of 205 patients with various Papanicolaou test results were enrolled to this study (negative, 26; atypical squamous cells of undetermined significance, 39; low grade squamous intraepithelial lesion, 44; high grade squamous intraepithelial lesion (HSIL), 48; and cancer, 48). DNA methylation analysis of four genes, ADCYAP1, PAX1, MAL, and CADM1, was performed on residual cervical cells from LBP samples using a quantitative bisulfite pyrosequencing method. To evaluate the diagnostic performance of the four methylated genes for cancer detection, receiver operating characteristic (ROC) curves were drawn. Sensitivities and specificities were also tested at cutoffs determined from the ROC curves. RESULTS: Cervical cancer cells showed dramatically increased methylation levels for the four genes analyzed. ADCYAP1 and PAX1 also trended toward elevated methylation levels in HSIL samples, although the levels were much lower than those in cancer cells. The sensitivities of methylated ADCYAP1, PAX1, MAL, and CADM1 for the detection of cancer were 79.2%, 75.0%, 70.8%, and 52.1%, and the specificities were 92.0%, 94.0%, 94.7%, and 94.0%, respectively. Methylated ADCYAP1 and PAX1 demonstrated relatively better discriminatory ability than did methylated MAL and CADM1 (area under the curves 0.911 and 0.916 vs. 0.854 and 0.756, respectively). CONCLUSION: DNA methylation status, especially in the ADCYAP1 and PAX1 genes, showed relatively good specificity, ranging from 90% to 94%. The possible additive and complementary roles of DNA methylation testing with respect to conventional cervical cancer screening programs will need to be validated in prospective population-based studies.
Alphapapillomavirus/genetics ; *Atypical Squamous Cells of the Cervix/pathology/virology ; Cell Adhesion Molecules/genetics ; *DNA Methylation ; Female ; Genotype ; Humans ; Immunoglobulins/genetics ; Myelin and Lymphocyte-Associated Proteolipid Proteins/genetics ; Paired Box Transcription Factors/genetics ; Papanicolaou Test ; Pituitary Adenylate Cyclase-Activating Polypeptide/genetics ; ROC Curve ; Squamous Intraepithelial Lesions of the Cervix/*genetics/pathology/virology ; Uterine Cervical Neoplasms/*genetics/pathology/virology ; Vaginal Smears

OBJECTIVE: To assess the outcome of the treatment of primary vaginal cancer using definitive radiotherapy (RT) and to evaluate the prognostic factors of survival. METHODS: The medical records of nine institutions were retrospectively reviewed to find the patients with vaginal cancer treated with definitive RT with or without chemotherapy. A total of 138 patients met the inclusion criteria. None had undergone curative excision. RESULTS: The median follow-up time of the survivors was 77.6 months and the median survival time was 46.9 months. The 5-year overall survival, cancer-specific survival (CSS), and progression-free survival (PFS) rates were 68%, 80%, and 68.7%, respectively. In the survival analysis, the multivariate analysis showed that a lower the International Federation of Gynecology and Obstetrics (FIGO) stage and prior hysterectomy were favorable prognostic factors of CSS, and a lower FIGO stage and diagnosed prior to year 2000 were favorable prognostic factors of PFS. In the subgroup analysis of the patients with available human papillomavirus (HPV) results (n=27), no statistically significant relationship between the HPV status and recurrence or survival was found. Grade 3 or 4 acute and late toxicity were present in 16 and 9 patients, respectively. The FIGO stage and the tumor size were predictors of severe late toxicity. CONCLUSION: The data clearly showed that a higher FIGO stage was correlated with a worse survival outcome and higher severe late toxicity. Therefore, precise RT and careful observation are crucial in advanced vaginal cancer. In this study, the HPV status was not related to the survival outcome, but its further investigation is needed.
Adult ; Aged ; Aged, 80 and over ; Brachytherapy ; Carcinoma, Squamous Cell/mortality/*radiotherapy/secondary/virology ; Chemoradiotherapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Hysterectomy ; Middle Aged ; Neoplasm Staging ; Papillomavirus Infections/diagnosis ; Radiotherapy/adverse effects ; Republic of Korea ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Tumor Burden ; Vaginal Neoplasms/mortality/pathology/*radiotherapy/virology

OBJECTIVETo investigate factors affecting the diagnostic accuracy of cervical liquid-based cytology for high-grade squamous intraepithelial lesion (HSIL).

METHODSA retrospective evaluation of cytological and histological slides was performed in 415 patients who had cytological HSIL between 2007 and 2010.

RESULTSAmong 42 209 cases screened by ThinPrep liquid-based cytology, 415 cases (1.0%) of HSIL were eventually identified. The mean age of HSIL patients was 41.6 years, and 30-49 years were the most common age group. Among 415 cases, 325 patients had available histological diagnosis as follows: 23 (7.1%) negative, 22 (6.8%) CIN1/HPV, 223 (68.6%) CIN2/CIN3, and 57 (17.5%) squamous cell carcinoma (SCC). The positive predictive values of HSIL to predict CIN2 (or higher grade of dysplasia) and CIN1 were 86.2% (280/325) and 92.9% (302/325), respectively. Inadequate biopsy, reactive glandular cells, islet atrophy, chemo/radiotherapy and others were responsible for the cytologically false-positive diagnosis. Fifty-seven (17.5%) cases of HSIL had a histological diagnosis of SCC. The possible causes of misdiagnosis were social factors, under-recognized cytological features of poorly-differentiated SCC and absence of typical diagnostic features in cytology slides.

CONCLUSIONSCytology of HSIL has a high positive predictive value for the presence of CIN2/CIN3 and SCC. Cytologists and gynecologists should be aware of the diagnostic pitfalls that may lead to the discrepancy between cytology and histology.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; diagnosis ; pathology ; Cervical Intraepithelial Neoplasia ; diagnosis ; pathology ; virology ; Cytological Techniques ; Diagnostic Errors ; Female ; Humans ; Mass Screening ; Middle Aged ; Papillomavirus Infections ; Retrospective Studies ; Uterine Cervical Neoplasms ; diagnosis ; pathology ; virology ; Young Adult

Carcinoma, Squamous Cell ; genetics ; pathology ; virology ; Cervical Intraepithelial Neoplasia ; genetics ; pathology ; virology ; DNA, Viral ; metabolism ; Female ; Gene Amplification ; Humans ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; Neoplasm Grading ; Neoplasm Staging ; Papillomaviridae ; genetics ; Papillomavirus Infections ; metabolism ; RNA ; genetics ; Telomerase ; genetics ; Uterine Cervical Neoplasms ; genetics ; pathology ; virology

OBJECTIVETo analyze the expression and clinical values of HPV L1 capsid protein and p16INK4a protein in uterine cervical lesions.

METHODSFifty-four cervical intraepithelial neoplasias CIN1, 44 CIN2, 78 CIN3, and 48 squamous cell carcinoma were included in this study. All CIN and squamous carcinomas were stained with anti-HPV L1 capsid protein antibodies and anti-p16INK4a antibody. Forty-five CIN1 patients were followed up for 6 years.

RESULTSForty-five CIN1 patients were followed up for 6 years, among them 6 cases showed a progression (One case changed to CIN3, 5 cases to CIN2). L1 positivity was found in 50 cases which decreased with CIN increasing (χ(2) = 259.923, P < 0.001) while p16INK4a positivity was found in 177 cases which co-increased with CIN (χ(2) = 48.842, P < 0.001). L1(-)p16INK4a (-) or L1(+)p16INK4a(-) appeared mainly in CIN1 while L1(-)p16INK4a(+) appeared mainly in CIN2 lesions. No progression was found in the group of L1(-)p16INK4a(-) CIN1 patients. The risk of CIN1 progression in L1(-)p16INK4a(+) group was 66.7% while L1(+)p16INK4a(-) group was 9.5%, and L1(+)p16INK4a(+) group was 33.3%.

CONCLUSIONSThe expression of p16INK4a together with HPV L1 are different in various cervical lesions, and the combined detection of p16INK4a and HPV L1 can be helpful for estimating the biological potentiality of CIN lesions.

Adult ; Aged ; Capsid Proteins ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; pathology ; virology ; Cervical Intraepithelial Neoplasia ; metabolism ; pathology ; virology ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; Middle Aged ; Oncogene Proteins, Viral ; metabolism ; Papillomavirus Infections ; Uterine Cervical Neoplasms ; metabolism ; pathology ; virology ; Young Adult

The diagnosis of postradiation nasopharyngeal skull base lesions in petients with nasopharyngeal carcinoma (NPC) is still a tough problem in clinical practice. An early and accurate diagnosis is important for subsequent management. We prospectively evaluated the diagnostic value of plasma Epstein-Barr virus(EBV) DNA in detecting postradiation nasopharyngeal skull base lesions in NPC patients. From July 2006 to September 2010, 90 patients with postradiation NPC (34 women and 56 men; median age: 42 years) met the selection criteria and were recruited in this study. All postradiation nasopharyngeal skull base lesions were found in the latest magnetic resonance imaging (MRI) examinations before endoscopic surgery, and the nasopharyngeal cavity was normal under flexible nasopharyngoscopy. Plasma EBV DNA detection was performed within 2 weeks before endoscopic surgery. A total of 90 endoscopic operations were successfully performed without any postoperative complications. Recurrences confirmed by postoperative pathology were found in 30 patients. The specificity, positive and negative predictive values of plasma EBV DNA detection were better than those of MRI. In addition, combining plasma EBV DNA detection with MRI improved the specificity and positive predictive values of MRI. Plasma EBV DNA detection followed by MRI would help to diagnose recurrence whereas MRI was unable. These results indicate that plasma EBV DNA is an effective and feasible biomarker for detecting postradiation nasopharyngeal skull base lesions in NPC patients.
Adult ; Carcinoma, Squamous Cell ; blood ; radiotherapy ; virology ; DNA, Viral ; blood ; Endoscopy ; Female ; Follow-Up Studies ; Herpesvirus 4, Human ; genetics ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; blood ; radiotherapy ; virology ; Nasopharynx ; pathology ; Neoplasm Recurrence, Local ; diagnosis ; virology ; Neoplasm, Residual ; Osteoradionecrosis ; diagnosis ; surgery ; Prospective Studies ; Skull Base ; pathology

OBJECTIVETo study the correlation of the expressions of CD82 and hTERT and HPV infection with the clinical pathological features of penile cancer and identify their prognostic significance in the lymphatic metastasis of the disease.

METHODSA total of 44 patients underwent partial or radical penectomy and lymph node dissection. The expressions of CD82 and hTERT were determined by immunohistochemistry, and HPV infection was detected by PCR.

RESULTSThe positive rates of CD82, hTERT, and HPV DNA in penile carcinoma were 47.7%, 38.6% and 25.9%, respectively. The amplified HPV DNA was HPV-16. The pathological stage and hTERT expression were positively correlated with inguinal lymph node metastasis of penile cancer (P = 0.032, P = 0.041), and so was the pathological stage with the expression of CD82 (P = 0.045), but neither the pathological stage, nor the expression of CD82 or the positive rate of HPV DNA showed any correlation with lymph node metastasis (P = 0.627, P = 0.094, P = 0.633).

CONCLUSIONThe pathological grade and hTERT expression are independent prognostic factors for lymph node metastasis in penile carcinoma. These features help the prognosis and identification of the patient at the risk of nodal metastasis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; metabolism ; pathology ; virology ; Humans ; Kangai-1 Protein ; metabolism ; Male ; Middle Aged ; Neoplasm Staging ; Papillomaviridae ; Papillomavirus Infections ; metabolism ; Penile Neoplasms ; metabolism ; pathology ; virology ; Telomerase ; metabolism

OBJECTIVETo study the difference in gene expression between human papillomavirus (HPV)16-positive and HPV-negative esophageal squamous cell carcinoma(ESCC) .

METHODSEight HPV 16-positive and seven HPV-negative ESCC specimens were evaluated by PCR. The samples were then determined for gene expression profiling using Solexa Sequencing Chip followed by bioinformatics analysis.

RESULTSA total of 796 differentially expressed genes between HPV 16-positive and HPV-negative ESCC were observed. Among them, 366 were up-regulated while 430 were down-regulated. Functional classification and pathway analysis showed that the functions of these genes were mostly related to tumor morphology, immune, and inflammatory response, cellular growth and proliferation and cellular movement. Of these, factors related to immune and inflammation were the most representative.

CONCLUSIONDifferences in immunologic factors may be associated with HPV infection in esophageal cancer.

Adult ; Aged ; Carcinoma, Squamous Cell ; genetics ; pathology ; virology ; Esophageal Neoplasms ; genetics ; pathology ; virology ; Female ; Gene Expression Profiling ; Human papillomavirus 16 ; genetics ; Humans ; Male ; Microarray Analysis ; Middle Aged ; Papillomaviridae ; genetics ; Papillomavirus Infections ; genetics

Adult ; Aged ; Carcinoma, Squamous Cell ; pathology ; virology ; Cervical Intraepithelial Neoplasia ; pathology ; virology ; Colposcopy ; Cytodiagnosis ; DNA Probes, HPV ; DNA, Viral ; isolation & purification ; Female ; Humans ; Middle Aged ; Nucleic Acid Hybridization ; Papillomaviridae ; genetics ; isolation & purification ; Papillomavirus Infections ; Uterine Cervical Neoplasms ; pathology ; virology ; Vaginal Smears ; Young Adult