OBJECTIVE: We conducted a pooled analysis of published studies to compare the performance of human papillomavirus (HPV) testing and cytology in detecting residual or recurrent diseases after treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3). METHODS: Source articles presenting data on posttreatment HPV testing were identified from the National Library of Medicine (PubMed) database. We included 5,319 cases from 33 articles published between 1996 and 2013. RESULTS: The pooled sensitivity of high-risk HPV testing (0.92; 95% confidence interval [CI], 0.90 to 0.94) for detecting posttreatment CIN 2 or worse (CIN 2+) was much higher than that of cytology (0.76; 95% CI, 0.71 to 0.80). Co-testing of HPV testing and cytology maximized the sensitivity (0.93; 95% CI, 0.87 to 0.96), while HPV genotyping (detection of the same genotype between pre- and posttreatments) did not improve the sensitivity (0.89; 95% CI, 0.82 to 0.94) compared with high-risk HPV testing alone. The specificity of high-risk HPV testing (0.83; 95% CI, 0.82 to 0.84) was similar to that of cytology (0.85; 95% CI, 0.84 to 0.87) and HPV genotyping (0.83; 95% CI, 0.81 to 0.85), while co-testing had reduced specificity (0.76; 95% CI, 0.75 to 0.78). For women with positive surgical margins, high-risk HPV testing provided remarkable risk discrimination between test-positives and test-negatives (absolute risk of residual CIN 2+ 74.4% [95% CI, 64.0 to 82.6] vs. 0.8% [95% CI, 0.15 to 4.6]; p<0.001). CONCLUSION: Our findings recommend the addition of high-risk HPV testing, either alone or in conjunction with cytology, to posttreatment surveillance strategies. HPV testing can identify populations at greatest risk of posttreatment CIN 2+ lesions, especially among women with positive section margins.
Cervical Intraepithelial Neoplasia/pathology/surgery/*virology ; Female ; Humans ; Neoplasm Recurrence, Local/*virology ; Neoplasm, Residual ; Papillomaviridae/*isolation & purification ; Papillomavirus Infections/complications/*diagnosis ; Predictive Value of Tests ; Risk Assessment/methods ; Sensitivity and Specificity ; Uterine Cervical Neoplasms/pathology/surgery/*virology

In 2015, fourteen topics were selected as major research advances in gynecologic oncology. For ovarian cancer, high-level evidence for annual screening with multimodal strategy which could reduce ovarian cancer deaths was reported. The best preventive strategies with current status of evidence level were also summarized. Final report of chemotherapy or upfront surgery (CHORUS) trial of neoadjuvant chemotherapy in advanced stage ovarian cancer and individualized therapy based on gene characteristics followed. There was no sign of abating in great interest in immunotherapy as well as targeted therapies in various gynecologic cancers. The fifth Ovarian Cancer Consensus Conference which was held in November 7–9 in Tokyo was briefly introduced. For cervical cancer, update of human papillomavirus vaccines regarding two-dose regimen, 9-valent vaccine, and therapeutic vaccine was reviewed. For corpus cancer, the safety concern of power morcellation in presumed fibroids was explored again with regard to age and prevalence of corpus malignancy. Hormone therapy and endometrial cancer risk, trabectedin as an option for leiomyosarcoma, endometrial cancer and Lynch syndrome, and the radiation therapy guidelines were also discussed. In addition, adjuvant therapy in vulvar cancer and the updated of targeted therapy in gynecologic cancer were addressed. For breast cancer, palbociclib in hormone-receptor-positive advanced disease, oncotype DX Recurrence Score in low-risk patients, regional nodal irradiation to internal mammary, supraclavicular, and axillary lymph nodes, and cavity shave margins were summarized as the last topics covered in this review.
Biomedical Research/*trends ; Breast Neoplasms/therapy ; Combined Modality Therapy ; Dioxoles ; Endometrial Neoplasms/therapy ; Female ; Genital Neoplasms, Female/genetics/*therapy ; Humans ; Immunotherapy ; Neoadjuvant Therapy ; Neoplasm Recurrence, Local ; Ovarian Neoplasms/prevention & control/therapy ; Papillomavirus Vaccines ; Precision Medicine ; Tetrahydroisoquinolines ; Uterine Cervical Neoplasms/prevention & control/therapy/virology ; Uterine Neoplasms/therapy

OBJECTIVE: To investigate the efficacy of submucosal resection by CO2 laser in the treatment of recurrent laryngeal papilloma and the effect on prognosis. METHOD: A total of 11 patients diagnosed as recurrent laryngeal papilloma were included in this review. Papilloma was marked before operation and checked under fibro-laryngoscope. Papilloma was resected completely including the submucosal tissure with CO2 laser or microequipment. In widespread papilloma, false membrane in raw surface were cleared 7-10 days after operation. Surgical specimens (including membrane) were detected by routine pathology, HPV typing and immunohistochemical pathologic examination. The patients were checked once a month in the first 3 months after operation, and then once for every 3 months. Once the hoarseness and other symptoms aggravated or the disease was recurrent, the patients were treated immediately. RESULT: HPV viral DNA was found in 10/11 cases, with HPV11 (7/11 cases) and HPV6 (3/11 cases). Cases with regards to follow-up, from 6 months to 1 year, 3 cases were followed up 1 year after operation, without recurrence. Five patients including 2 children were followed up 6 to 12 months after operation, without recurrence. Two children underwent 2 or 3 operations, were followed-up more than 6 months withouting recurrence. CONCLUSION Papilloma submucosal resection could decrease postoperative recurrence and is worth to be further investigated.
Child ; DNA, Viral ; blood ; Human papillomavirus 11 ; isolation & purification ; Human papillomavirus 6 ; isolation & purification ; Humans ; Laryngeal Neoplasms ; diagnosis ; surgery ; Laryngoscopes ; Lasers, Gas ; Neoplasm Recurrence, Local ; Papilloma ; diagnosis ; surgery ; virology ; Papillomavirus Infections ; diagnosis ; surgery ; Postoperative Period ; Prognosis ; Respiratory Tract Infections ; diagnosis ; surgery

OBJECTIVETo study the relationship between metastasis or recurrence of hepatocellular carcinoma (HCC) and hepatitis B virus (HBV) DNA load or the presence of double mutation at 1762/1764 in the basic core promoter (BCP).

METHODSOne-hundred-and-fifty-seven patients with HCC were included in the study. Events of tumor metastasis or recurrence were recorded during 120 weeks of clinical follow-up after treatment by surgery or transarterial chemoembolization (TACE). The 1-year follow-up included monthly alpha fetoprotein (AFP) measurement and abdominal ultrasonography (US), as well as helical computed tomographic (CT) scan performed every 3 months. Follow-up beyond 1-year (surveillance) included AFP measurement and abdominal US every 2 months and helical CT scan every 6 months. Suspected metastasis or recurrence was investigated by hepatic angiography and confirmed according to the combined imaging findings. Serum HBV DNA level was measured by real-time PCR. HBV genotypes were determined by PCR-restriction fragment length polymorphism analysis.

RESULTSOf the 157 HCC cases 110 experienced tumor metastasis or recurrence; the cumulative probability of post-treatment HCC metastasis or recurrence was 4 (2.55%) at week 12, 14 (8.92%) at week 24, 28 (17.83%) at week 48, 64 (40.76%) at week 72, 92 (58.60%) at week 96, and 110 (70.06%) at week 120. Multivariate analysis indicated that both the BCP 1762/1764 double mutations and HBV DNA levels were risk factors for HCC recurrence or metastasis. In particular, the incidence of HCC recurrence or metastasis increased with baseline serum HBV DNA levels in a dose-response manner, ranging from 8/19 (42.1%) for less than 3 log10 copies/ml HBV DNA to 35/61 (57.3%) for 3-5 log10 copies/ml and 67/77 (87.0%) for more than 5 log10 copies/ml. After adjusting for potential confounders, serum HBV DNA level remained independently associated with HCC metastasis or recurrence. HCC recurrence or metastasis occurred in 22/43 (51.2%) of patients without BCP 1762/1764 mutations and 88/114 (77.2%) of patients with BCP 1762/1764 mutations. The adjusted odds ratio for patients infected with BCP 1762/1764 double mutation HBV, compared with those infected with non-BCP 1762/1764 mutation HBV, was 5.264 (95% CI: 1.436-12.574, P less than 0.05).

CONCLUSIONInfection with HBV carrying the BCP 1762/1764 double mutation and presence of high HBV DNA load are independent risk factors for developing HCC metastasis or recurrence after surgery or TACE.

Adult ; Aged ; Carcinoma, Hepatocellular ; pathology ; virology ; DNA, Viral ; blood ; Female ; Genotype ; Hepatitis B Core Antigens ; genetics ; Hepatitis B virus ; genetics ; Humans ; Liver Neoplasms ; pathology ; virology ; Male ; Middle Aged ; Mutation ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Promoter Regions, Genetic ; Viral Load

OBJECTIVETo investigate the relationship between HPV-DNA status and p16 protein expression in oropharyngeal squamous cell carcinoma (OSCC) and their clinical significance.

METHODSSixty-six patients with oropharyngeal squamous cell carcinomas treated in the Cancer Hospital of Chinese Academy of Medical Sciences from Jan. 1999 to Dec. 2009 were included in this study. Their formalin-fixed and paraffin-embedded tumor tissue blocks met the eligibility criteria and were used in this study. A "sandwich" technique was used to prepare paraffin sections for HPV-DNA analysis. HPV-DNA was detected using the SPF10 LiPA25 version 1 assay. The expression of p16 protein was detected by immunohistochemistry. The survival rates of patients with different HPV-DNA and p16 protein status were analyzed.

RESULTSHPV-DNA was detected in 11 (16.7%) of all specimens. Expression of p16 protein was detected in 9 of the 11 patients with HPV-positive tumors, and in 12 patients of 55 HPV-negative tumors. The expression of p16 protein was highly correlated with the presence of HPV-DNA (P < 0.001). The tumors were classified into three groups based on the p16 protein expression and HPV-DNA status: group A (9 patients): HPV(+) and p16 protein(+); group B (14 patients): HPV-DNA(+)/p16 protein(-) or HPV-DNA(-)/p16 protein(+); and group C (43 patients): HPV-DNA(-)/p16 protein(-). The 3-year OS rates of these 3 groups were 100%, 77.8% and 42.0% (P = 0.001), and their DSS rates were 100%, 77.8% and 46.4%, respectively(P = 0.004).

CONCLUSIONSIn oropharyngeal squamous cell carcinomas, p16 protein expression is highly correlated with the presence of HPV-DNA, and might be a surrogate marker for HPV-positive OSCC. Combination of p16 protein and HPV-DNA status detection may help to more accurately stratify oropharyngeal carcinomas and predict their prognosis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; genetics ; metabolism ; virology ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; DNA, Viral ; isolation & purification ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Oropharyngeal Neoplasms ; genetics ; metabolism ; virology ; Papillomaviridae ; Papillomavirus Infections ; genetics ; metabolism ; Survival Rate

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 investigate the expression of CK19 in HBV-related hepatocellular carcinoma (HCC) tissues in patients with low serum AFP concentration and the relationship between them and the recurrence and prognosis of HCC after R0 radical hepatectomy.

METHODSThe expressions of CK19 and Ki67 in HCC tissues of 235 cases were examined using tissue microarray and two-step methods of PV-6000 immunohistochemistry. The expression of CK19 mRNA in 20 frozen HCC specimens was examined by RT-PCR. The correlation between gene expressions and tumor recurrence and prognosis was analyzed.

RESULTSAmong the 235 HBV-related HCC patients after R0 radical hepatectomy, the median disease-free survival (DFS) was 31.2 months in the patients with serum AFP < 400 µg/L and 13.8 months in the patients with serum AFP ≥ 400 µg/L (P = 0.041), the overall survival (OS) was 84.0 and 58.6 months in the two subgroups (P = 0.125), and the tumor recurrence within one year was in 43 cases (27%) and 37 cases (49.3%), respectively, (P = 0.001). The DFS was 11.6 months in the CK19-positive cases and 27.0 months in the CK19-negative cases (P > 0.05). The OS was significantly lower in the CK19-positive cases than that in the CK19-negative cases (P = 0.023). Both DFS and OS in the CK19-positive cases with AFP < 400 µg/L were significantly lower than those in the CK19-negative cases with AFP < 400 µg/L (both P < 0.05). The CK19 expression was significantly correlated with histological differentiation (P = 0.023), number of tumor foci (P = 0.044), vascular tumor embolism (P = 0.005), regional lymph node metastasis (P = 0.023), and 1-year recurrence (P = 0.006). Among the patients with AFP < 400 µg/L, the 1-year recurrence was 53% in the CK19-positive cases and 23% in the CK19-negative cases (P < 0.001), the median DFS was 11.3 months in CK19-positive cases and 34.0 months in CK19-negative cases (P = 0.010), and the median OS was 19.5 months in the CK19-positive cases, significantly lower than 84.0 months in the CK19-negative cases (P = 0.001). Cox regression analysis showed that CK19-positive expression was an independent factor affecting early HCC recurrence and prognosis.

CONCLUSIONIn HBV-related HCC patients after radical hepatectomy with AFP < 400 µg/L, positive expression of CK19 indicates a higher proliferation and invasiveness of HCC, and is an important factor of early recurrence and poor prognosis.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; metabolism ; pathology ; surgery ; virology ; Disease-Free Survival ; Female ; Hepatectomy ; methods ; Hepatitis B virus ; Humans ; Keratin-19 ; genetics ; metabolism ; Liver Neoplasms ; metabolism ; pathology ; surgery ; virology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; RNA, Messenger ; metabolism ; Survival Rate ; Young Adult ; alpha-Fetoproteins ; metabolism

OBJECTIVETo clarify the expression and clinical significance of metastasis-associated in colon cancer 1 (MACC1) mRNA in hepatocellular carcinoma (HCC).

METHODSThe expression and distribution of MACC1 were assessed by quantitative real-time polymerase chain reaction (RT-PCR) and immunohistochemical staining (IHC) in a cohort of hepatitis B virus-related HCC, including 138 in early (A), 96 in intermediate (B) and 120 in advanced stages (C). The association of MACC1 mRNA with disease progression and outcomes was analyzed by univariate and multivariate Cox analysis.

RESULTSThe intratumoral expressions of MACC1 mRNA in HCC stage I (0.001 76, range: 0.000 54 - 0.002 47), stage II (0.002 49, range: 0.000 55 - 0.006 78) and stage III (0.008 35, range: 0.006 86 - 0.009 88) were about 3-, 4- and 14-fold higher than that in the normal liver tissue (0.000 59, range: 0.000 57 - 0.000 60), respectively. Intratumoral expression of MACC1 mRNA increased with disease progression from stage I to stage III. HCC clinical staging classification, age, portal vein invasion and tumor differentiation were significantly associated with intratumoral high expression of MACC1 mRNA (All P < 0.05). Immunohistochemical staining showed that there was an increased MACC1 expression in cytoplasm of HCC cells and positive nuclear staining in some cases. Increased MACC1 mRNA expression could predict poor outcome and recurrence in stage A and B HCC postoperatively. The median tumor-free survival and total survival of patients with high MACC1 mRNA expression were 34.0 and 40 months, respectively, significantly lower than that in those with low expression (48.0 and 48.0 months) (all P < 0.01). Cox analysis showed that Child-Pugh grading and high expression of MACC1 mRNA were independent predictive factors, and high expression of MACC1 was an independent predictive factor affecting the tumor-free survival.

CONCLUSIONSMACC1 mRNA up-regulation is a feature of disease progression in HCC. MACC1 mRNA expression in the HCC may become an independent predictive factor for recurrence and survival in postoperative HCC patients.

Adult ; Aged ; Carcinoma, Hepatocellular ; metabolism ; pathology ; virology ; DNA, Viral ; analysis ; Disease-Free Survival ; Female ; Follow-Up Studies ; Hepatitis B virus ; Humans ; Liver Neoplasms ; metabolism ; pathology ; virology ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Proportional Hazards Models ; RNA, Messenger ; metabolism ; Real-Time Polymerase Chain Reaction ; Survival Rate ; Transcription Factors ; genetics ; metabolism ; Up-Regulation ; Young Adult

OBJECTIVETo investigate the relationship between hepatocellular carcinoma (HCC) recurrence and hepatitis B virus (HBV) recurrence.

METHODSThe clinical data of 340 patients underwent liver transplantation due to HBV related end-stage liver disease and received long-term follow up in our hospital from Jan 2004 to Dec 2008 were retrospectively analyzed. All patients received nucleoside analogues therapy formally before entering into the waiting list and nucleoside analogues combined low-dose HBIG therapy during and after transplantation. Patients were regularly followed up at the outpatient, monitoring the HBV recurrence and survival. Multivariate Cox regression analysis was used to evaluate the risk factors for hepatitis recurrence.

RESULTS33 patients suffered from HBV recurrence post transplantation. The 1-, 3- and 5- year recurrence rates were 7.0%, 10% and 13% respectively. The median HBV recurrence time was 5 months (1-21 months). COX regression analysis revealed that risk factors for HBV recurrence were HCC (HR = 2.98; 95% CI 1.08-8.25; P < 0.05) and pre-transplantation HBV-DNA load over 5 log10 copies/ml (HR = 3.99; 95% CI 1.85-8.62; P < 0.01). Further stratified analysis showed that patients who suffered from carcinoma recurrence had a higher incidence of HBV recurrence than those who did not, which were 27.9% and 8.7% (HR = 4.58;95% CI 1.88-11.12; P < 0.01) respectively. 12 patients suffered from both HCC and HBV recurrence. Spearman correlation analysis demonstrated a strong correlation between HBV and HCC recurrence times (r = 0.583, P < 0.05).

CONCLUSIONSPost transplantation HCC recurrence is a risk factor for HBV recurrence.

Adult ; Carcinoma, Hepatocellular ; pathology ; virology ; Female ; Hepatitis B ; complications ; Hepatitis B virus ; Humans ; Liver Neoplasms ; pathology ; virology ; Liver Transplantation ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; etiology ; Retrospective Studies ; Risk Factors

In the last decade, we have gained significant understanding of the mechanism by which vesicular stomatitis virus (VSV) specifically kills cancer cells. Dysregulation of translation and defective innate immunity are both thought to contribute to VSV oncolysis. Safety and efficacy are important objectives to consider in evaluating VSV as a therapy for malignant disease. Ongoing efforts may enable VSV virotherapy to be considered in the near future to treat drug-resistant ovarian cancer when other options have been exhausted. In this article, we review the development of VSV as a potential therapeutic approach for recurrent or drug-resistant ovarian cancer.
Animals ; Antineoplastic Agents ; pharmacology ; Apoptosis ; Cell Proliferation ; Drug Resistance, Neoplasm ; Female ; Humans ; Neoplasm Recurrence, Local ; Oncolytic Virotherapy ; methods ; Ovarian Neoplasms ; pathology ; therapy ; virology ; Vesicular stomatitis Indiana virus ; physiology ; Virus Replication