Ten-Year Follow-up of 9-Valent Human Papillomavirus Vaccine: Immunogenicity, Effectiveness, and Safety.

Background And Objectives: The 9-valent human papillomavirus (9vHPV) vaccine Phase III immunogenicity study in 9- to 15-year-old boys and girls was extended to assess immunogenicity and effectiveness through 10 years after the last vaccine dose (NCT00943722).

Methods: Boys (n = 301) and girls (n = 971) who received three 9vHPV vaccine doses in the base study (day 1, months 2 and 6) enrolled in the extension. Serum was collected through month 126 for antibody assessments by competitive Luminex immunoassay and immunoglobulin G-Luminex immunoassay.

Efficacy, immunogenicity, and safety of a quadrivalent HPV vaccine in men: results of an open-label, long-term extension of a randomised, placebo-controlled, phase 3 trial.

Background: The quadrivalent human papillomavirus (HPV) vaccine was shown to prevent infections and lesions related to HPV6, 11, 16, and 18 in a randomised, placebo-controlled study in men aged 16-26 years. We assessed the incidences of external genital warts related to HPV6 or 11, and external genital lesions and anal dysplasia related to HPV6, 11, 16, or 18, over 10 years of follow-up.

Methods: The 3-year base study was an international, multicentre, double-blind, randomised, placebo-controlled trial done at 71 sites in 18 countries.

Risk of specific types of ovarian cancer after borderline ovarian tumors in Denmark: A nationwide study.

Population-based evidence regarding risk of ovarian cancer after a borderline ovarian tumor (BOT) is sparse. We aimed to examine the incidence of specific types of ovarian cancer in women with serous or mucinous BOTs in a nationwide cohort study with up to 36 years of follow-up. Using the nationwide Danish Pathology Data Bank, we identified 4,281 women with a BOT (2,058 serous BOTs and 2,223 mucinous BOTs) in Denmark during 1978-2012.

Two types of primary mucinous ovarian tumors can be distinguished based on their origin.

The origin of primary mucinous ovarian tumors is unknown. We explore the hypothesis that they originate from either Brenner tumors or teratomas and examine differences between the tumors that arise in these settings. A total of 104 Brenner tumor-associated mucinous tumors and 58 teratoma-associated mucinous tumors were analyzed.

Clinicopathologic and Molecular Features of Paired Cases of Metachronous Ovarian Serous Borderline Tumor and Subsequent Serous Carcinoma.

Although risk factors have been established for the development of serous carcinoma after a diagnosis of serous borderline tumor (SBT), comprising atypical proliferative serous tumor (APST) (ie, conventional SBT) and noninvasive low-grade serous carcinoma (niLGSC) (ie, micropapillary SBT), subsequent invasive carcinoma still occurs in a subset of women who are not at increased risk. Whether subsequent serous carcinoma in women with a prior SBT represents malignant progression/recurrence or an independent primary tumor is unclear, and the combined clinicopathologic and molecular features of SBTs and their subsequent carcinomas have not been fully characterized. In this study, we analyzed a cohort of 42 women initially diagnosed with SBT who subsequently developed serous carcinoma of a total of 1025 cases of ovarian SBT from a nationwide population-based cohort.

Nine-valent HPV vaccine efficacy against related diseases and definitive therapy: comparison with historic placebo population.

Objective: Nine-valent human papillomavirus (9vHPV) vaccine efficacy against disease and cervical surgeries related to all nine vaccine components was assessed compared with a historic placebo population. This was not assessed in the 9vHPV vaccine efficacy trial since the trial was quadrivalent HPV (qHPV) vaccine-controlled, efficacy was measured for the five HPV types covered only by 9vHPV vaccine (HPV31/33/45/52/58), but not the four types covered by both vaccines (HPV6/11/16/18).

Methods: Three international, randomized, double-blind studies were conducted using the same methodology.

Intratumoral Heterogeneity Accounts for Apparent Progression of Noninvasive Serous Tumors to Invasive Low-grade Serous Carcinoma: A Study of 30 Low-grade Serous Tumors of the Ovary in 18 Patients With Peritoneal Carcinomatosis.

Noninvasive ovarian low-grade serous tumors [atypical proliferative serous tumor (APST)/serous borderline tumor] appear to progress to invasive low-grade serous carcinoma (LGSC) at a low but regular rate. The underlying biology of this phenomenon is unknown. We studied 18 patients with 30 ovarian tumors (12 bilateral), including APST, noninvasive LGSC and invasive LGSC, who also had low-grade serous carcinomatosis.

Fallopian Tube Lesions in Women at High Risk for Ovarian Cancer: A Multicenter Study.

The prognosis of women diagnosed with invasive high-grade serous ovarian carcinoma (HGSC) is poor. More information about serous tubal intraepithelial carcinoma (STIC) and serous tubal intraepithelial lesions (STIL), putative precursor lesions of HGSC, could inform prevention efforts. We conducted a multicenter study to identify risk/protective factors associated with STIC/STILs and characterize p53 signatures in the fallopian tube.

Human Papillomavirus Genotypes From Vaginal and Vulvar Intraepithelial Neoplasia in Females 15-26 Years of Age.

Objective: To estimate the proportion of vulvar and vaginal low-grade and high-grade squamous intraepithelial lesions (LSILs and HSILs) in females 15-26 years of age attributable to 14 human papillomavirus (HPV) genotypes (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59).

Methods: A post hoc analysis of prospectively diagnosed vulvar and vaginal LSILs and HSILs among females 15-26 years of age enrolled in the placebo arms of two phase 3, randomized HPV vaccine trials assessed 14 prespecified HPV genotypes associated with cervical cancers or anogenital warts using a type-specific multiplex polymerase chain reaction assay. The frequency of lesions associated with specific HPV genotypes was estimated by proportional and other attribution methods.

Comprehensive Surgical Staging in Stage 1 Clear Cell and Endometrioid Ovarian Carcinomas: Is it Necessary?

The objective of this article was to evaluate the presence of occult metastasis after comprehensive surgical staging of clear cell ovarian carcinoma (CCC) and endometrioid ovarian carcinoma (EMCA) that appeared to be confined to the ovary at time of surgery. Between 1998 to 2016, 85 patients with CCC and EMCA were identified who were comprehensively staged and felt to be stage 1 intraoperatively. Of the 85 patients who underwent surgical staging, 4 (4.

Evaluation of liquid from the Papanicolaou test and other liquid biopsies for the detection of endometrial and ovarian cancers.

We report the detection of endometrial and ovarian cancers based on genetic analyses of DNA recovered from the fluids obtained during a routine Papanicolaou (Pap) test. The new test, called PapSEEK, incorporates assays for mutations in 18 genes as well as an assay for aneuploidy. In Pap brush samples from 382 endometrial cancer patients, 81% [95% confidence interval (CI), 77 to 85%] were positive, including 78% of patients with early-stage disease.

High grade serous ovarian carcinomas originate in the fallopian tube.

High-grade serous ovarian carcinoma (HGSOC) is the most frequent type of ovarian cancer and has a poor outcome. It has been proposed that fallopian tube cancers may be precursors of HGSOC but evolutionary evidence for this hypothesis has been limited. Here, we perform whole-exome sequence and copy number analyses of laser capture microdissected fallopian tube lesions (p53 signatures, serous tubal intraepithelial carcinomas (STICs), and fallopian tube carcinomas), ovarian cancers, and metastases from nine patients.

Molecular analysis of high-grade serous ovarian carcinoma with and without associated serous tubal intra-epithelial carcinoma.

Many high-grade serous carcinomas (HGSCs) of the pelvis are thought to originate in the distal portion of the fallopian tube. Serous tubal intra-epithelial carcinoma (STIC) lesions are the putative precursor to HGSC and identifiable in ~ 50% of advanced stage cases. To better understand the molecular etiology of HGSCs, we report a multi-center integrated genomic analysis of advanced stage tumors with and without STIC lesions and normal tissues.

Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years: a randomised, double-blind trial.

Background: Primary analyses of a study in young women aged 16-26 years showed efficacy of the nine-valent human papillomavirus (9vHPV; HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine against infections and disease related to HPV 31, 33, 45, 52, and 58, and non-inferior HPV 6, 11, 16, and 18 antibody responses when compared with quadrivalent HPV (qHPV; HPV 6, 11, 16, and 18) vaccine. We aimed to report efficacy of the 9vHPV vaccine for up to 6 years following first administration and antibody responses over 5 years.

Methods: We undertook this randomised, double-blind, efficacy, immunogenicity, and safety study of the 9vHPV vaccine study at 105 study sites in 18 countries.

Atypical Proliferative (Borderline) Serous Tumor in the Brain: A Case Report.

A 59-year-old woman with a remote history of invasive ductal carcinoma of the breast was found on a follow-up computed tomography scan of her brain to have a 1-cm lesion in the right frontal lobe in 2008. In the ensuing years, before her current admission, multiple imaging studies of the brain revealed that the lesion was stable and it was, therefore, interpreted as a small area of encephalomalacia related to a thrombosed cortical vein, a cavernoma, or treated metastatic breast cancer. In 2013, the patient underwent a bilateral salpingo-oophorectomy for ovarian tumors that were diagnosed as bilateral serous cystadenofibromas.

Long-term Behavior of Serous Borderline Tumors Subdivided Into Atypical Proliferative Tumors and Noninvasive Low-grade Carcinomas: A Population-based Clinicopathologic Study of 942 Cases.

Ovarian serous borderline tumors (SBTs) have been the subject of considerable controversy, particularly with regard to terminology and behavior. It has been proposed that they constitute a heterogenous group of tumors composed, for the most part, of typical SBTs that are benign and designated "atypical proliferative serous tumor (APST)" and a small subset of SBTs with micropapillary architecture that have a poor outcome and are designated "noninvasive low-grade serous carcinoma (niLGSC)". It also has been argued that the difference in behavior between the 2 groups is not due to the subtype of the primary tumor but rather the presence of extraovarian disease, specifically invasive implants.

Parity, infertility, oral contraceptives, and hormone replacement therapy and the risk of ovarian serous borderline tumors: A nationwide case-control study.

Objective: Few studies have examined the risk of an ovarian serous borderline tumor (SBT) associated with parity, infertility, oral contraceptives (OCs), or hormone replacement therapy (HRT), which was the study aim.

Methods: This nationwide case-control study included all women with an SBT diagnosis in Denmark, 1978-2002. SBTs were confirmed by centralized expert pathology review.

Steroid hormone synthesis by the ovarian stroma surrounding epithelial ovarian tumors: a potential mechanism in ovarian tumorigenesis.

Epithelial ovarian tumors are responsive to steroid hormone stimulation and the ovarian stroma may have a direct role in this process. We evaluated immunohistochemical markers of sex-steroid differentiation and steroidogenesis (calretinin, inhibin, steroidogenic factor 1), steroid enzymes involved in hormone biosynthesis (CYP17, CYP19, HSD17β1, AKR1C3), and hormone receptors (estrogen receptor, progesterone receptor, and androgen receptor) in 101 epithelial ovarian tumors and in normal structures implicated in ovarian carcinogenesis (ovarian surface epithelium and cortical inclusion cysts) in an attempt to elucidate this process. We hypothesized that ovarian stroma immediately adjacent to tumors express markers of sex-steroid differentiation and steroidogenesis and steroid enzymes whereas the epithelium contains corresponding hormone receptors.

A nationwide study of ovarian serous borderline tumors in Denmark 1978-2002. Risk of recurrence, and development of ovarian serous carcinoma.

Objective: Absolute risk and risk factors for recurrence and ovarian serous carcinoma following ovarian serous borderline tumors (SBTs) is not well-established.

Methods: We included all women with SBTs in Denmark, 1978-2002. Diagnoses were confirmed by centralized pathology review and classified as atypical proliferative serous tumor (APST) or noninvasive low-grade serous carcinoma (LGSC).

CCNE1 amplification and centrosome number abnormality in serous tubal intraepithelial carcinoma: further evidence supporting its role as a precursor of ovarian high-grade serous carcinoma.

Aberration in chromosomal structure characterizes almost all cancers and has profound biological significance in tumor development. It can be facilitated by various mechanisms including overexpression of cyclin E1 and centrosome amplification. As ovarian high-grade serous carcinoma has pronounced chromosomal instability, in this study we sought to determine whether increased copy number of CCNE1 which encodes cyclin E1 and centrosome amplification (>2 copies) occurs in its putative precursor, serous tubal intraepithelial carcinoma.

Diagnostic potential of tumor DNA from ovarian cyst fluid.

We determined whether the mutations found in ovarian cancers could be identified in the patients' ovarian cyst fluids. Tumor-specific mutations were detectable in the cyst fluids of 19 of 23 (83%) borderline tumors, 10 of 13 (77%) type I cancers, and 18 of 18 (100%) type II cancers. In contrast, no mutations were found in the cyst fluids of 18 patients with benign tumors or non-neoplastic cysts.

PD-L1 Expression in Human Placentas and Gestational Trophoblastic Diseases.

One of the major immune checkpoints responsible for immune evasion in cancer cells is the interaction between programmed cell death-1 (PD-1) and its ligand (PD-L1). As human trophoblastic cells display many of the features of malignant cells such as the ability to invade normal tissue including blood vessels and are apparently not eradicated by the host immune system, we undertook the present study to determine whether PD-L1 was upregulated in different types of trophoblastic cells during normal pregnancy and in gestational trophoblastic diseases. Immunohistochemistry using an anti-PD-L1-specific antibody demonstrated that in early and term normal placentas, PD-L1 was highly expressed in syncytiotrophoblast and to a much lower extent in intermediate trophoblastic cells located in the chorion laeve and implantation site.

The Dualistic Model of Ovarian Carcinogenesis: Revisited, Revised, and Expanded.

Since our proposal of a dualistic model of epithelial ovarian carcinogenesis more than a decade ago, a large number of molecular and histopathologic studies were published that have provided important insights into the origin and molecular pathogenesis of this disease. This has required that the original model be revised and expanded to incorporate these findings. The new model divides type I tumors into three groups: i) endometriosis-related tumors that include endometrioid, clear cell, and seromucinous carcinomas; ii) low-grade serous carcinomas; and iii) mucinous carcinomas and malignant Brenner tumors.