Alpha-tocopherol and alpha-tocopheryl quinone levels in cervical intraepithelial neoplasia and cervical cancer.

PubMed

Palan, Prabhudas R; Woodall, Angela L; Anderson, Patrick S; Mikhail, Magdy S

2004-05-01

alpha-Tocopherol is a potent antioxidant that protects cell membranes against oxidative damage. Red blood cell alpha-tocopherol levels reflect membrane alpha-tocopherol concentrations, and altered levels may suggest membrane damage. The objective of this study was to determine the levels of alpha-tocopherol and alpha-tocopheryl quinone, the oxidized product of alpha-tocopherol, in plasma and red blood cells that were obtained from control subjects and patients with cervical intraepithelial neoplasia and cervical cancer. In this cross-sectional study, 72 women, (32 African American and 40 Hispanic) were recruited. Among these subjects, 37 women had cervical intraepithelial neoplasia; 14 women had cervical cancer, and 21 women were considered control subjects, who had normal Papanicolaou test results. alpha-Tocopherol and alpha-tocopheryl quinone levels were determined in red blood cell and plasma by high-pressure liquid chromatography. Plasma levels of alpha-tocopherol and alpha-tocopheryl quinone were decreased significantly (P=.012 and=.005, respectively, by Kruskal-Wallis test) in study groups compared with the control group; red blood cell levels of alpha-tocopherol and alpha-tocopheryl quinone were not altered significantly. The lower alpha-tocopherol level that was observed in this study is consistent with our previous reports of decreased antioxidant concentrations and increased oxidative stress in women with cervical intraepithelial neoplasia. Unaltered red blood cell alpha-tocopherol and alpha-tocopheryl quinone levels suggest undamaged cell membrane. Further studies are needed to investigate the potential role of oxidative stress in cervical intraepithelial neoplasia.

Clinicopathologic analysis of 370 cases of vulvar intraepithelial neoplasia. Italian Study Group on Vulvar Disease.

PubMed

1996-09-01

To investigate epidemiologic, clinical and pathologic aspects of various grades of vulvar intraepithelial neoplasia (VIN). A retrospective, multicenter study of 370 cases of vulvar intraepithelial neoplasia (VIN) was performed by the Italian Study Group on Vulvar Disease. Of the 370 cases, 148 were VIN 1 (40.0%, 53 were VIN 2 (14.3%), and 169 were VIN 3 (45.7%). The mean age of the patients was 52.6 years. During the study period an increase in the rate of human papillomavirus-associated VIN was observed. In addition, while VIN 1 and 2 were associated mostly with squamous cell hyperplasia, VIN 3 was almost equally associated with lichen sclerosus and squamous cell hyperplasia; the difference was statistically significant. Intraepithelial or invasive squamous neoplasia of the lower genital tract was associated in 22% of the cases (82/370). The results of the investigation, although not allowing firm conclusions due to the retrospective and multicentered nature of the study, demonstrate the extreme heterogeneity of VIN lesions.

A Clinical and Pathological Overview of Vulvar Condyloma Acuminatum, Intraepithelial Neoplasia, and Squamous Cell Carcinoma

PubMed Central

Léonard, Boris; Kridelka, Frederic; Delbecque, Katty; Goffin, Frederic; Demoulin, Stéphanie; Doyen, Jean; Delvenne, Philippe

2014-01-01

Condyloma acuminatum, intraepithelial neoplasia, and squamous cell carcinoma are three relatively frequent vulvar lesions. Condyloma acuminatum is induced by low risk genotypes of human papillomavirus (HPV). Vulvar intraepithelial neoplasia (VIN) and squamous cell carcinoma have different etiopathogenic pathways and are related or not with high risk HPV types. The goal of this paper is to review the main pathological and clinical features of these lesions. A special attention has been paid also to epidemiological data, pathological classification, and clinical implications of these diseases. PMID:24719870

Progression From Perianal High-Grade Anal Intraepithelial Neoplasia to Anal Cancer in HIV-Positive Men Who Have Sex With Men.

PubMed

Tinmouth, Jill; Peeva, Valentina; Amare, Henok; Blitz, Sandra; Raboud, Janet; Sano, Marie; Steele, Leah; Salit, Irving E

2016-09-01

High-grade intraepithelial neoplasia is known to progress to invasive squamous-cell carcinoma of the anus. There are limited reports on the rate of progression from high-grade intraepithelial neoplasia to anal cancer in HIV-positive men who have sex with men. The purpose of this study was to describe in HIV-positive men who have sex with men with perianal high-grade intraepithelial neoplasia the rate of progression to anal cancer and the factors associated with that progression. This was a prospective cohort study. The study was conducted at an outpatient clinic at a tertiary care center in Toronto. Thirty-eight patients with perianal high-grade anal intraepithelial neoplasia were identified among 550 HIV-positive men who have sex with men. All of the patients had high-resolution anoscopy for symptoms, screening, or surveillance with follow-up monitoring/treatment. We measured the incidence of anal cancer per 100 person-years of follow-up. Seven (of 38) patients (18.4%) with perianal high-grade intraepithelial neoplasia developed anal cancer. The rate of progression was 6.9 (95% CI, 2.8-14.2) cases of anal cancer per 100 person-years of follow-up. A diagnosis of AIDS, previously treated anal cancer, and loss of integrity of the lesion were associated with progression. Anal bleeding was more than twice as common in patients who progressed to anal cancer. There was the potential for selection bias and patients were offered treatment, which may have affected incidence estimates. HIV-positive men who have sex with men should be monitored for perianal high-grade intraepithelial neoplasia. Those with high-risk features for the development of anal cancer may need more aggressive therapy.

Surgical interventions for high grade vulval intraepithelial neoplasia

PubMed Central

Kaushik, Sonali; Pepas, Litha; Nordin, Andy; Bryant, Andrew; Dickinson, Heather O

2014-01-01

Background Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin. This uncommon chronic skin condition of the vulva is associated with a high risk of recurrence and the potential to progress to vulval cancer. The condition is complicated by its’ multicentric and multifocal nature. The incidence of this condition appears to be rising particularly in the younger age group. There is a lack of consensus on the optimal surgical treatment method. However, the rationale for surgical treatment of VIN has been to treat symptoms and exclude underlying malignancy with the continued aim of preservation of vulval anatomy and function. Repeated treatments affect local cosmesis and cause psychosexual morbidity thus impacting on the patients’ quality of life. Objectives To evaluate the effectiveness and safety of surgical interventions for high grade VIN. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 3, 2010, Cochrane Gynaecological Cancer Group Trials Register, MEDLINE and EMBASE up to September 2010. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that compared surgical interventions, in adult women diagnosed with high grade vulval intraepithelial neoplasia. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Main results We found only one RCT which included 30 women that met our inclusion criteria and this trial reported data on carbon dioxide laser (CO2 laser) versus ultrasonic surgical aspiration (USA). There was no statistically significant difference in the risk of disease recurrence after one year follow-up, pain, presence of scarring, dysuria or burning, adhesions, infection, abnormal discharge and eschar between women who received CO2 laser and those who received USA. The trial

Disease progression and recurrence in women treated for vulvovaginal intraepithelial neoplasia

PubMed Central

Baumann, Marc; Mueller, Michael; Fink, Daniel; Heinzl, Siegfried; Imesch, Patrick; Dedes, Konstantin

2013-01-01

Objective The malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease. Methods Four hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results Of the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality. Conclusion Laser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary. PMID:23875073

A Simple Laparoscopic Procedure to Restore a Normal Vaginal Length After Colpohysterectomy With Large Upper Colpectomy for Cervical and/or Vaginal Neoplasia.

PubMed

Leblanc, Eric; Bresson, Lucie; Merlot, Benjamin; Puga, Marco; Kridelka, Frederic; Tsunoda, Audrey; Narducci, Fabrice

2016-01-01

Colpohysterectomy is sometimes associated with a large upper colpectomy resulting in a shortened vagina, potentially impacting sexual function. We report on a preliminary experience of a laparoscopic colpoplasty to restore a normal vaginal length. Patients with shortened vaginas after a laparoscopic colpohysterectomy were considered for a laparoscopic modified Davydov's procedure to create a new vaginal vault using the peritoneum of the rectum and bladder. From 2010 to 2014, 8 patients were offered this procedure, after informed preoperative consent. Indications were 2 extensive recurrent vaginal intraepithelial neoplasias grade 3 and 6 radical hysterectomies for cervical cancer. Mean vaginal length before surgery was 3.8 cm (standard deviation, 1.6). Median operative time was 50 minutes (range, 45-90). Blood loss was minimal (50-100 mL). No perioperative complications occurred. Median vaginal length at discharge was 11.3 cm (range, 9-13). Sexual intercourse could be resumed around 10 weeks after surgery. At a median follow-up of 33.8 months (range, 2.4-51.3), 6 patients remained sexually active but 2 had stopped. Although this experience is small, this laparoscopic modified Davydov's procedure seems to be an effective procedure, adaptable to each patient's anatomy. If the initial postoperative regular self-dilatation is carefully observed, vaginal patency is durably restored and enables normal sexual function. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

Screening, Surveillance, and Treatment of Anal Intraepithelial Neoplasia.

PubMed

Long, Kevin C; Menon, Raman; Bastawrous, Amir; Billingham, Richard

2016-03-01

The prevalence of anal intraepithelial neoplasia has been increasing, especially in high-risk patients, including men who have sex with men, human immunodeficiency virus positive patients, and those who are immunosuppressed. Several studies with long-term follow-up have suggested that rate of progression from high-grade squamous intraepithelial lesions to invasive anal cancer is ∼ 5%. This number is considerably higher for those at high risk. Anal cytology has been used to attempt to screen high-risk patients for disease; however, it has been shown to have very little correlation to actual histology. Patients with lesions should undergo history and physical exam including digital rectal exam and standard anoscopy. High-resolution anoscopy can be considered as well, although it is of questionable time and cost-effectiveness. Nonoperative treatments include expectant surveillance and topical imiquimod or 5-fluorouracil. Operative therapies include wide local excision and targeted ablation with electrocautery, infrared coagulation, or cryotherapy. Recurrence rates remain high regardless of treatment delivered and surveillance is paramount, although optimal surveillance regimens have yet to be established.

Screening, Surveillance, and Treatment of Anal Intraepithelial Neoplasia

PubMed Central

Long, Kevin C.; Menon, Raman; Bastawrous, Amir; Billingham, Richard

2016-01-01

The prevalence of anal intraepithelial neoplasia has been increasing, especially in high-risk patients, including men who have sex with men, human immunodeficiency virus positive patients, and those who are immunosuppressed. Several studies with long-term follow-up have suggested that rate of progression from high-grade squamous intraepithelial lesions to invasive anal cancer is ∼ 5%. This number is considerably higher for those at high risk. Anal cytology has been used to attempt to screen high-risk patients for disease; however, it has been shown to have very little correlation to actual histology. Patients with lesions should undergo history and physical exam including digital rectal exam and standard anoscopy. High-resolution anoscopy can be considered as well, although it is of questionable time and cost–effectiveness. Nonoperative treatments include expectant surveillance and topical imiquimod or 5-fluorouracil. Operative therapies include wide local excision and targeted ablation with electrocautery, infrared coagulation, or cryotherapy. Recurrence rates remain high regardless of treatment delivered and surveillance is paramount, although optimal surveillance regimens have yet to be established. PMID:26929753

Differentiated Vulvar Intraepithelial Neoplasia-like and Lichen Sclerosus-like Lesions in HPV-associated Squamous Cell Carcinomas of the Vulva.

PubMed

Rakislova, Natalia; Alemany, Laia; Clavero, Omar; Del Pino, Marta; Saco, Adela; Quirós, Beatriz; Lloveras, Belen; Alejo, Maria; Halec, Gordana; Quint, Wim; de Sanjosé, Silvia; Ordi, Jaume

2018-06-01

Most human papillomavirus (HPV)-associated vulvar squamous cell carcinomas (VSCCs) originate from high-grade squamous intraepithelial lesions, also named usual type vulvar intraepithelial neoplasia. However, growing evidence suggests that morphologic studies have limitations in predicting HPV status in vulvar lesions. We aimed to evaluate adjacent intraepithelial lesions in a series of DNA HPV-positive VSCCs, focusing on unusual histologic patterns mimicking differentiated vulvar intraepithelial neoplasia (dVIN) or lichen sclerosus (LS). We identified 326 DNA HPV-positive VSCC with at least 1 cm of skin adjacent to the invasive tumor and analyzed HPV typing, HPV E6*I mRNA, and p16 immunohistochemistry in all cases. A careful histologic evaluation was conducted. A conclusive association with HPV was based on a positive p16 or HPV E6*I mRNA result or both in addition to the HPV DNA, whereas cases negative for both markers were classified as nonconclusively associated with HPV. One hundred twenty-one tumors (37.1%) had normal adjacent skin, 191 (58.6%) had only high-grade squamous intraepithelial lesions, also named usual type vulvar intraepithelial neoplasia, and unusual intraepithelial lesions were identified in 14 (4.3%) tumors. Seven cases showed dVIN-like features, 5 showed adjacent LS-like lesion, and in 2 cases dVIN-like and LS-like lesions were identified simultaneously. Six of them were conclusively associated with HPV (3 dVIN-like, 2 LS-like, 1 with combined dVIN/LS-like features). All 6 tumors were associated with HPV16 and were positive for both p16 and HPV mRNA, and p16 was also positive in the dVIN-like and LS-like lesions. In summary, a small subset of VSCCs conclusively associated with HPV may arise on intraepithelial lesions, mimicking precursors of HPV-independent VSCC.

Keratosis reduces sensitivity of anal cytology in detecting anal intraepithelial neoplasia.

PubMed

ElNaggar, Adam C; Santoso, Joseph T; Xie, Huiwen Bill

2012-02-01

To identify factors that may contribute to poor sensitivity of anal cytology in contrast to the sensitivity of anoscopy in heterosexual women. We analyzed 324 patients with biopsy confirmed diagnosis of genital intraepithelial neoplasia (either vulva, vaginal, or cervical) from 2006 to 2011 who underwent both anal cytology and anoscopy. Cytology, anoscopy, and biopsy results were recorded. Biopsy specimens underwent independent analysis for quality of specimen. Also, biopsy specimens were analyzed for characteristics that may contribute to correlation, or lack thereof, between anal cytology and anoscopic directed biopsy. 133 (41%) patients had abnormal anoscopy and underwent directed biopsy. 120 patients with normal anal cytology had anoscopy directed biopsies, resulting in 58 cases of AIN (sensitivity 9.4%; 0.039-0.199). This cohort was noted to have extensive keratosis covering the entire dysplastic anal lesion. 18 patients yielded abnormal anal cytology. Of these patients, 13 had anoscopic directed biopsies revealing 6 with AIN and absent keratosis (specificity 88.6%; 0.78-0.95). The κ statistic for anal cytology and anoscopy was -0.0213 (95% CI=-0.128-0.086). Keratosis reduces the sensitivity of anal cytology. Furthermore, anal cytology poorly correlates with anoscopy in the detection of AIN (κ statistic=-0.0213). Copyright © 2011 Elsevier Inc. All rights reserved.

Penile intraepithelial neoplasia and other premalignant lesions of the penis.

PubMed

Crispen, Paul L; Mydlo, Jack H

2010-08-01

Invasive penile cancer is an aggressive malignancy that often requires partial or complete penile amputation. Premalignant penile lesions, such as penile intraepithelial neoplasia, will have been present prior to the development of invasive disease in a substantial percentage of patients. Early detection and treatment of premalignant penile lesions may prevent malignant progression while avoiding penile amputation. This review focuses on premalignant penile lesions and the associations of these lesions with the development of invasive penile cancer. Copyright 2010 Elsevier Inc. All rights reserved.

Photodynamic therapy of cervical intraepithelial neoplasia

NASA Astrophysics Data System (ADS)

Inada, Natalia M.; Lombardi, Welington; Leite, Marieli F. M.; Trujillo, Jose R.; Kurachi, Cristina; Bagnato, Vanderlei S.

2014-03-01

Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors, especially in Gynecology. The photodynamic reaction is based on the production of reactive oxygen species after the activation of a photosensitizer. Advantages of the PDT in comparison to the surgical resection are: ambulatory treatment and tissue recovery highly satisfactory, through a non-invasive procedure. The cervical intraepithelial neoplasia (CIN) grades I and II presents potential indications for PDT. The aim of the proposed study is to evaluate the safety and efficacy of the PDT for the diagnostics and treatment of CIN I and II. The equipment and the photosensitizer are produced in Brazil with a representative low cost. It is possible to visualize the fluorescence of the cervix and to treat the lesions, without side effects. The proposed clinical protocol shows great potential to become a public health technique.

[Usefulness of human papillomavirus testing in anal intraepithelial neoplasia screening in a risk behaviour population].

PubMed

Padilla-España, Laura; Repiso-Jiménez, Bosco; Fernández-Sánchez, Fernando; Frieyro-Elicegui, Marta; Fernández-Morano, Teresa; Pereda, Teresa; Rivas-Ruiz, Francisco; Redondo, Maximino; de-Troya Martín, Magdalena

2014-11-01

The incidence of intraepithelial anal neoplasia is increasing in certain risk behaviour groups, and human papillomavirus (HPV) infection is involved in its pathogenesis. The systematic use of anal cytology, and more recently HPV detection by hybrid capture and genotyping, have been introduced into screening programs in recent decades. A retrospective cohort study was carried out on individuals with risk behaviours of developing intraepithelial anal neoplasia and who attended Sexually Transmitted Infections clinics in the Dermatology area of the Hospital Costa del Sol from January 2010 to December 2012. The intraepithelial anal neoplasia screening was performed using anal cytology and HPV genotyping. Half (50%) of the study population were HIV positive. A high frequency of anal dysplasia and presence of HPV in cytology (82.1%) and genotype (79%) was found. A statistically significant association (P<.005) was obtained between the presence of high-risk HPV genotypes and the presence of high-grade dysplasia in the second directed cytology. HPV genotyping enabled 17 cases (22%) of severe dysplasia to be identified that were under-diagnosed in the first cytology. Cases of high-grade dysplasia can be under-diagnosed by a first anal cytology. Detection of HPV can supplement this procedure, leading to the identification of those patients most at risk of developing high-grade anal dysplasia. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Intracellular signaling entropy can be a biomarker for predicting the development of cervical intraepithelial neoplasia.

PubMed

Sato, Masakazu; Kawana, Kei; Adachi, Katsuyuki; Fujimoto, Asaha; Yoshida, Mitsuyo; Nakamura, Hiroe; Nishida, Haruka; Inoue, Tomoko; Taguchi, Ayumi; Ogishima, Juri; Eguchi, Satoko; Yamashita, Aki; Tomio, Kensuke; Wada-Hiraike, Osamu; Oda, Katsutoshi; Nagamatsu, Takeshi; Osuga, Yutaka; Fujii, Tomoyuki

2017-01-01

While the mortality rates for cervical cancer have been drastically reduced after the introduction of the Pap smear test, it still is one of the leading causes of death in women worldwide. Additionally, studies that appropriately evaluate the risk of developing cervical lesions are needed. Therefore, we investigated whether intracellular signaling entropy, which is measured with microarray data, could be useful for predicting the risks of developing cervical lesions. We used three datasets, GSE63514 (histology), GSE27678 (cytology) and GSE75132 (cytology, a prospective study). From the data in GSE63514, the entropy rate was significantly increased with disease progression (normal < cervical intraepithelial neoplasia, CIN < cancer) (Kruskal-Wallis test, p < 0.0001). From the data in GSE27678, similar results (normal < low-grade squamous intraepithelial lesions, LSILs < high-grade squamous intraepithelial lesions, HSILs ≤ cancer) were obtained (Kruskal-Wallis test, p < 0.001). From the data in GSE75132, the entropy rate tended to be higher in the HPV-persistent groups than the HPV-negative group. The group that was destined to progress to CIN 3 or higher had a tendency to have a higher entropy rate than the HPV16-positive without progression group. In conclusion, signaling entropy was suggested to be different for different lesion statuses and could be a useful biomarker for predicting the development of cervical intraepithelial neoplasia.

Intracellular signaling entropy can be a biomarker for predicting the development of cervical intraepithelial neoplasia

PubMed Central

Sato, Masakazu; Adachi, Katsuyuki; Fujimoto, Asaha; Yoshida, Mitsuyo; Nakamura, Hiroe; Nishida, Haruka; Inoue, Tomoko; Taguchi, Ayumi; Ogishima, Juri; Eguchi, Satoko; Yamashita, Aki; Tomio, Kensuke; Wada-Hiraike, Osamu; Oda, Katsutoshi; Nagamatsu, Takeshi; Osuga, Yutaka; Fujii, Tomoyuki

2017-01-01

While the mortality rates for cervical cancer have been drastically reduced after the introduction of the Pap smear test, it still is one of the leading causes of death in women worldwide. Additionally, studies that appropriately evaluate the risk of developing cervical lesions are needed. Therefore, we investigated whether intracellular signaling entropy, which is measured with microarray data, could be useful for predicting the risks of developing cervical lesions. We used three datasets, GSE63514 (histology), GSE27678 (cytology) and GSE75132 (cytology, a prospective study). From the data in GSE63514, the entropy rate was significantly increased with disease progression (normal < cervical intraepithelial neoplasia, CIN < cancer) (Kruskal-Wallis test, p < 0.0001). From the data in GSE27678, similar results (normal < low-grade squamous intraepithelial lesions, LSILs < high-grade squamous intraepithelial lesions, HSILs ≤ cancer) were obtained (Kruskal-Wallis test, p < 0.001). From the data in GSE75132, the entropy rate tended to be higher in the HPV-persistent groups than the HPV-negative group. The group that was destined to progress to CIN 3 or higher had a tendency to have a higher entropy rate than the HPV16-positive without progression group. In conclusion, signaling entropy was suggested to be different for different lesion statuses and could be a useful biomarker for predicting the development of cervical intraepithelial neoplasia. PMID:28453530

Vulvar intraepithelial neoplasia--the need for auditable measures of management.

PubMed

Athavale, Ram; Naik, R; Godfrey, K A; Cross, P; Hatem, M H; de Barros Lopes, A

2008-03-01

Surgical excision is currently the standard treatment for vulvar intraepithelial neoplasia (VIN). To date it has proved difficult to evaluate the management of VIN in reported series due to heterogeneity in datasets. The objective of this study was to justify standardised data presentation to permit comparison between series and facilitate determination of an optimal strategy for management of VIN. We propose auditable indicators of performance to benchmark management and outcomes. This may also enable definition of a surgical control arm for future novel therapy studies. Data from the Northern Gynaecological Oncology Centre (NGOC), UK on women with proven VIN diagnosed between 1989 and 2004 who attended the vulvar review clinic are presented and analysed alongside three large retrospective series by Jones et al. [Jones RW, Rowan DM, Stewart AW. Vulvar intraepithelial neoplasia: aspects of the natural history and outcome in 405 women. Obstet Gynecol 2005;106(6):1319-26], Herod et al. [Herod JJ, Shafi MI, Rollason TP, Jordan JA, Luesley DM. Vulvar intraepithelial neoplasia: long term follow up of treated and untreated women. Br J Obstet Gynaecol 1996;103(5):446-52], McNally et al. [McNally OM, Mulvany NJ, Pagano R, Quinn MA, Rome RM. VIN 3: a clinicopathologic review. Int J Gynecol Cancer 2002;12(5):490-5] against proposed performance indicators to illustrate the deficiencies in current data presentation. Demographics and indicators such as degree of pathological expertise, definition of early stromal invasion and use of International Society for the study of Vulvovaginal Disease (ISSVD) classification were usually well documented. The description of lesions including size and focality were not always documented, nor the proportion examined by co-specialists. Numbers of primary treatments were well described but the indications for treatment, completeness of excision and VIN subclassification were not. Subsequent surgical treatments were inconsistently reported

Vaginal Speculum For Photodynamic Therapy And Method Of Using The Same

DOEpatents

Tadir, Yona; Berns, Michael W.; Monk, Brad J.; Profeta, Glen; Tromberg, Bruce J.

1995-10-17

An improved vaginal speculum for photodynamic therapy of intraepithelial tissue and in particular vaginal, cervical and vulvar neoplasia utilizes a precisely and accurately positionable optic fiber through which a predetermined dose of light in the range of 620 to 700 nanometers is delivered over a controlled area which has been previously treated with photodynamic therapeutic substances. In particular, the neoplastic area has been treated with hematoporphyrin derivatives and other photosensitizers which are selectively taken into the cancerous tissue. Exposure to the appropriate wavelength laser light photoactivates the absorbed hematoporphyrins causing the release of singlet oxygen which internally oxidizes and ultimately causes cell death. The fiber optic tip from which the laser light is transmitted is precisely positioned within the body cavity at a predetermined distance from the intraepithelial neoplasia in order to obtain the appropriate spot size and location to minimize damage to healthy tissue and maximize damage to the selectively impregnated cancerous tissue.

Local cytokine profiles of patients with cervical intraepithelial and invasive neoplasia.

PubMed

Peghini, Bethânea Crema; Abdalla, Douglas Reis; Barcelos, Ana Cristina Macedo; Teodoro, Lívia das Graças Vieito Lombardi; Murta, Eddie Fernando Candido; Michelin, Márcia Antoniazi

2012-09-01

Several studies have suggested that patients with cervical intraepithelial and invasive neoplasia have reduced levels of Th1 cytokines, and increased levels of Th2 cytokines. Thus, the aim of this study was to delineate the immunological profile associated with lesion progression. Biopsies were obtained from 28 patients with low grade cervical intraepithelial lesions (LSILs), 53 patients with high grade cervical intraepithelial lesions (HSILs), 25 patients with invasive cancer (CA), and 20 healthy controls. Levels of IFN-γ, TNF-α, IL-2, IL-4, IL-10, IL-12, TGF-β1 and TGF-β2 were then assayed by RT-PCR and ELISA for each biopsy sample. For LSILs, higher levels of Th1 cytokines were detected, while HSILs were associated with a Th2 cytokine profile. In contrast, CA tissues were associated with the strongest expression of a Treg cytokine profile. In conclusion the most important contribution of these work is identification of the Treg cytokine profile in HPV progression lesions and in combination, these results suggested that tumor progression is dependent on suppression of cellular immunity. Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

[Crosssectional survey of human papilloma virus subtype distribution and cervical intraepithelial neoplasia in Shenzhen].

PubMed

Liang, Ling-yun; Du, Hui; Wang, Chun; Zhang, Wei; Chen, Yun; Qu, Xin-feng; Yang, Bin; Wu, Bo; Wu, Ruo-song; Belinson, Jerome L; Wu, Rui-fang

2013-02-18

To investigate the prevalence of human papilloma virus (HPV) infection and cervical intraepithelial neoplasia (CIN) and pathogenecity of the HPV subtyping and virus loads in Shenzhen district. In the study, 10 000 sexually active women from Shenzhen city and rural areas around were screened for cervical cancer, and all the cases were examined with cytology tests and several kinds of high risk HPV (HR-HPV) tests. Those with cytology ≥atypical squamous cells of undetermined sign (ASC-US) or positive HPV results underwent colposcopy with biopsy for a pathological diagnosis. The average age of this study population was 38.9 years. The total prevalence of HPV infection was 16.6%, with age-specific prevalence increasing with age. The morbidity rate of the low grade cervical intraepithelial neoplasia CIN1 was 17.0%, but that with those aged ≥55 years showed a sharp drop. The morbidity rate of the high grade cervical intraepithelial neoplasia CIN2/3 was 2.6%, and was higher in the 45 to 59 years age group than in the 25 to 44 years age group. HR-HPV infection was an obvious relevant factor of CIN1 and CIN2/3, and the OR values increased as the virus loads increased, but they had different relevant HPV subtypes. We found that HPV-16, -58, -31, -33, -18 were the first five ones for CIN2/3 while HPV-39, -58, -59, -52, -66 for CIN1. There is a high level of HPV infection and CIN in Shenzhen district. The prevalence of HPV infection has a trend to increase with age, and the people aged 45 years and more are key objects for CIN2/3 screening, with the virus load and subtyping of HR-HPV infection as indicative factors.

Clinical and Economic Value of p16INK4a for the Differential Diagnosis of Morphologic Cervical Intraepithelial Neoplasia 2.

PubMed

Fishkel, Vanina S; Monge, Fernando C; von Petery, Felicitas M; Tapper, Karen E; Peña, Teresa M; Torres, Florencia; Poletta, Fernando A; Elgart, Jorge F; Avagnina, Alejandra; Denninghoff, Valeria

2018-05-04

The detection of high-grade intraepithelial lesions requires highly sensitive and specific methods that allow more accurate diagnoses. This contributes to a proper management of preneoplastic lesions, thus avoiding overtreatment. The purpose of this study was to analyze the value of immunostaining for p16 in the morphologic assessment of cervical intraepithelial neoplasia 2 lesions, to help differentiate between low-grade (p16-negative) and high-grade (p16-positive) squamous intraepithelial lesions. The direct medical cost of the treatment of cervical intraepithelial neoplasia 2 morphologic lesions was estimated. A retrospective observational cross-sectional study was carried out. This study analyzed 46 patients treated with excisional procedures because of cervical intraepithelial neoplasia 2 lesions, using loop electrosurgical excision procedures. Immunostaining for the biomarker was performed. For the estimation of overtreatment, percentages (%) and their 95% confidence interval were calculated. Of the 41 patients analyzed, 32 (78%) showed overexpression of p16 and 9 (22%) were negative (95% confidence interval, 11%-38%). Mean follow-up was 2.9 years, using cervical cytology testing (Pap) and colposcopy. High-risk human papillomavirus DNA tests were performed in 83% of patients. These retrospective results reveal the need for larger biopsy samples, which would allow a more accurate prediction of lesion risk. Considering the cost of p16 staining, and assuming the proper management of the low-grade lesion, an average of US$919 could be saved for each patient with a p16-negative result, which represents a global direct cost reduction of 10%.

Secondary prevention of cervical cancer part 3: evidence-based management of women with cervical intraepithelial neoplasia.

PubMed

Guido, Richard; Lonky, Neal M; Diedrich, Justin

2014-06-01

The management of cervical intraepithelial neoplasia has evolved over the last 20 years. Observation has replaced aggressive therapy in many cases. Evidence based guidelines now guide therapy. This chapter presents an overview of various treatment options, as well as the most recent guidelines of therapy.

Carbon dioxide laser management cervical intraepithelial neoplasia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bellina, J.H.; Wright, V.C.; Voros, J.I.

1981-12-01

In this report we describe the use of the carbon dioxide laser for the outpatient management of cervical intraepithelial neoplasia (CIN). A comparison of treatment effectiveness for different grades of CIN is also included. Two hundred fifty-six cases were evaluated by colposcopy, cytology, and histopathology, treated by at least 5 to 6 mm of laser vaporization, and followed up for an average of 10.7 months. Follow-up examinations included cytology, colposcopy, and directed biopsy if a suspicious lesion was discovered. During the follow-up, 18 cases of persistent CIN were identified (7.0%). Most of these were successfully managed with repeat laser treatment.more » Overall success of laser surgery for CIN, one or two applications, was 97.6%. Few complications were encountered. Laser surgery appears to offer acceptable treatment effectiveness, early identification of persistent disease, and easy retreatment when required. (Am. J. Obstet. Gynecol. 141:828, 1981.)« less

A systematic review of the prevalence and attribution of human papillomavirus types among cervical, vaginal, and vulvar precancers and cancers in the United States.

PubMed

Insinga, Ralph P; Liaw, Kai-Li; Johnson, Lisa G; Madeleine, Margaret M

2008-07-01

To describe prevalence and estimated attribution of human papillomavirus (HPV) types in U.S. cervical, vaginal, and vulvar precancers and cancers. U.S. studies reporting HPV typing for cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), and vaginal intraepithelial neoplasia (VaIN) and/or invasive cancers of those sites were gathered from the PubMed database (http://www.ncbi.nlm.nih.gov/sites/entrez/). Selected studies had PCR testing data for > or =10 cases for a disease endpoint. Analytic methods augmented prior reviews of cervical disease with an updated and expanded analysis (including vulvar and vaginal disease), new selection criteria for specimens, and adjustment for histologic type, where possible, among pooled cancer cases. In addition, for analyses of estimated attribution of HPV types, we incorporated accounting methods for lesions infected with multiple HPV types. Data from 22 U.S. studies meeting review eligibility criteria were tabulated. Following adjustment for the presence of multiple HPV types in a single specimen, the top two HPV types contributing to disease were CIN 1 (HPV 16/66; 15.3%), CIN 2/3 (HPV 16/31; 61.9%), cervical cancer (HPV 16/18; 79.2%), VIN 1 (HPV 6/11; 41.7%), VIN 3 (HPV 16/18; 84.0%), vulvar cancer (HPV 16/33; 55.5%), VaIN 3 (HPV 16/18; 65.1%), and vaginal cancer (HPV 16/18; 72.7%). The HPV type distribution and proportion of cases testing positive for any HPV type were observed to vary among U.S. cervical, vulvar, and vaginal neoplasias and by grade of disease. Adjustment for the presence of multitype HPV infections can have an important effect on the estimated attribution of HPV types to disease, particularly for types other than HPV 16.

Effectiveness of cryotherapy treatment for cervical intraepithelial neoplasia.

PubMed

Luciani, Silvana; Gonzales, Miguel; Munoz, Sergio; Jeronimo, Jose; Robles, Sylvia

2008-05-01

To assess the effectiveness of cryotherapy treatment delivered by general practitioners in primary care settings, as part of a screen-and-treat approach for cervical cancer prevention. Women aged between 25 and 49 years residing in San Martin, Peru, who were positive on visual inspection screening were treated, if eligible, with cryotherapy following biopsy. At 12 months post cryotherapy treatment the participants were evaluated for treatment effectiveness and examined by visual inspection and Papanicolaou test and, if positive, referred to a gynecologist for colposcopy and biopsy. Cryotherapy treatment was performed for 1398 women; of these, 531 (38%) had a histology result of cervical intraepithelial neoplasia (CIN). Cryotherapy effectively cured CIN in 418 (88%) women, including 49 (70%) women with a baseline diagnosis of CIN 3. Cryotherapy is an effective treatment for cervical precancerous lesions; it can easily be administered by general practitioners in primary care settings following visual inspection screening.

[Treatment of cervical intraepithelial neoplasia using the CO2 laser].

PubMed

Trejo Solorzano, O; González Iñiguez, R

1991-04-01

The use of laser therapy in CIN, is a practical method that has revolutionized the treatment of a very common pathology, that is the cervical neoplasia in its early stages. 86 patients with different stages of cervical intraepithelial neoplasia, were studied. Patients in groups I (45 patients) y II (28 patients), were submitted to a vaporization crater of the whole transformation zone because of having the cervical canal free of lesion. In group III (13 patients), a cylinder of the cervix was done to perform histological study, whether the cervical canal was compromised or not. The cytology control results for group I were excellent; from (45 patients) who came to 3-month check-up 79.1% of the whole presented negative II. For group II (28 patients), in first pap smear two patients (7.1%) had CIN, the rest of smears were reported 66% negative II, and in the 30.6% negative I. For the group III 14.2% (5 patients) of the whole had abnormal results, the rest of the smears 73.5% of the results reported negative II. The incidence of failure for this procedure is similar to that of hysterectomy with the same therapeutic goal .

Loss of Sirt1 Promotes Prostatic Intraepithelial Neoplasia, Reduces Mitophagy, and Delays Park2 Translocation to Mitochondria

PubMed Central

Di Sante, Gabriele; Pestell, Timothy G.; Casimiro, Mathew C.; Bisetto, Sara; Powell, Michael J.; Lisanti, Michael P.; Cordon-Cardo, Carlos; Castillo-Martin, Mireia; Bonal, Dennis M.; Debattisti, Valentina; Chen, Ke; Wang, Liping; He, Xiaohong; McBurney, Michael W.; Pestell, Richard G.

2016-01-01

Prostatic intraepithelial neoplasia is a precursor to prostate cancer. Herein, deletion of the NAD+-dependent histone deacetylase Sirt1 induced histological features of prostatic intraepithelial neoplasia at 7 months of age; these features were associated with increased cell proliferation and enhanced mitophagy. In human prostate cancer, lower Sirt1 expression in the luminal epithelium was associated with poor prognosis. Genetic deletion of Sirt1 increased mitochondrial superoxide dismutase 2 (Sod2) acetylation of lysine residue 68, thereby enhancing reactive oxygen species (ROS) production and reducing SOD2 activity. The PARK2 gene, which has several features of a tumor suppressor, encodes an E3 ubiquitin ligase that participates in removal of damaged mitochondria via mitophagy. Increased ROS in Sirt1−/− cells enhanced the recruitment of Park2 to the mitochondria, inducing mitophagy. Sirt1 restoration inhibited PARK2 translocation and ROS production requiring the Sirt1 catalytic domain. Thus, the NAD+-dependent inhibition of SOD2 activity and ROS by SIRT1 provides a gatekeeper function to reduce PARK2-mediated mitophagy and aberrant cell survival. PMID:25529796

[Prevalence of HPV-induced lesions in the anal canal among women with cervical intraepithelial neoplasia 2 and 3: cross-sectional study].

PubMed

Heráclio, Sandra de Andrade; de Araujo, Thaís Antunes; Souza, Alex Sandro Rolland; Cahen, Kristiane; Lima Junior, Sergio Ferreira; de Souza, Paulo Roberto Eleutério; Amorim, Melania Maria Ramos

2015-10-01

To determine the prevalence of HPV-induced lesions in the anal canal of women with cervical intraepithelial neoplasia (CIN) grade 2/3. A cross-sectional study was carried out from December 2008 to June 2009, in Pernambuco, northeastern Brazil. Only women with grade 2/3 CIN were included, and those who could not undergo anoscopy during their first visit were excluded. A cyttobrush was used for sample collection in order to identify HPV DNA through PCR and anal cytology. An anal biopsy was obtained in cases of abnormal anal cytology or major alterations in high resolution anoscopy (HRA). Thirty-two percent (n=37/115) of HRA were normal and 63.5% (n=73/115) showed acetowhite epithelium. Twenty-two percent (n=26/115) of anal cytologies were abnormal. Among the latter, 12.2% (n=14/26) were low-grade anal intraepithelial lesions and 3.4% (n=4/26) were high-grade anal intraepithelial lesions. Twenty-two anal biopsies were performed, 13.7% of which (n=3/22) were grade 2 anal intraepithelial neoplasia (AIN2) and 9% (n=2/22) were grade 3 AIN. Th HPV DNA was identified in 72.1% of cases (n=83/115). Women with CIN grade 2/3 showed a high prevalence of anal HPV infection and HPV-induced lesions.

Genetic Progression of High Grade Prostatic Intraepithelial Neoplasia to Prostate Cancer.

PubMed

Jung, Seung-Hyun; Shin, Sun; Kim, Min Sung; Baek, In-Pyo; Lee, Ji Youl; Lee, Sung Hak; Kim, Tae-Min; Lee, Sug Hyung; Chung, Yeun-Jun

2016-05-01

Although high grade prostatic intraepithelial neoplasia (HGPIN) is considered a neoplastic lesion that precedes prostate cancer (PCA), the genomic structures of HGPIN remain unknown. Identification of the genomic landscape of HGPIN and the genomic differences between HGPIN and PCA that may drive the progression to PCA. We analyzed 20 regions of paired HGPIN and PCA from six patients using whole-exome sequencing and array-comparative genomic hybridization. Somatic mutation and copy number alteration (CNA) profiles of paired HGPIN and PCA were measured and compared. The number of total mutations and CNAs of HGPINs were significantly fewer than those of PCAs. Mutations in FOXA1 and CNAs (1q and 8q gains) were detected in both HGPIN and PCA ('common'), suggesting their roles in early PCA development. Mutations in SPOP, KDM6A, and KMT2D were 'PCA-specific', suggesting their roles in HGPIN progression to PCA. The 8p loss was either 'common' or 'PCA-specific'. In-silico estimation of evolutionary ages predicted that HGPIN genomes were much younger than PCA genomes. Our data show that PCAs are direct descendants of HGPINs in most cases that require more genomic alterations to progress to PCA. The nature of heterogeneous HGPIN population that might attenuate genomic signals should further be studied. HGPIN genomes harbor relatively fewer mutations and CNAs than PCA but require additional hits for the progression. In this study, we suggest a systemic diagram from high grade prostatic intraepithelial neoplasia (HGPIN) to prostate cancer (PCA). Our results provide a clue to explain the long latency from HGPIN to PCA and provide useful information for the genetic diagnosis of HGPIN and PCA. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Multiphoton imaging of low grade, high grade intraepithelial neoplasia and intramucosal invasive cancer of esophagus

NASA Astrophysics Data System (ADS)

Xu, Jian; Jiang, Liwei; Kang, Deyong; Wu, Xuejing; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, Jiangbo; Chen, Jianxin

2017-04-01

Esophageal squamous cell carcinoma (ESCC) is devastating because of its aggressive lymphatic spread and clinical course. It is believed to occur through low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and intramucosal invasive cancer (IMC) before transforming to submucosal cancer. In particular, these early lesions (LGIN, HGIN and IMC), which involve no lymph node nor distant metastasis, can be cured by endoscopic treatment. Therefore, early identification of these lesions is important so as to offer a curative endoscopic resection, thus slowing down the development of ESCC. In this work, spectral information and morphological features of the normal esophageal mucosa are first studied. Then, the morphological changes of LGIN, HGIN and IMC are described. Lastly, quantitative parameters are also extracted by calculating the nuclear-to-cytoplasmic ratio of epithelial cells and the pixel density of collagen in the lamina propria. These results show that multiphoton microscopy (MPM) has the ability to identify normal esophageal mucosa, LGIN, HGIN and IMC. With the development of multiphoton endoscope systems for in vivo imaging, combined with a laser ablation system, MPM has the potential to provide immediate pathologic diagnosis and curative treatment of ESCC before the transformation to submucosal cancer in the future.

Rapid spontaneous regression of acute-onset vulvar intraepithelial neoplasia 3 in young women: a case series.

PubMed

Stephenson, Ruth D; Denehy, Thad R

2012-01-01

Vulvar intraepithelial neoplasia 3 (VIN 3)/vulvar carcinoma in situ is currently treated by surgical excision, laser ablation, or topically with 5-fluorouracil or imiquimod. The rate of progression of untreated VIN 3/vulvar carcinoma in situ to invasive cancer is significant, although difficult to assess, because most patients undergo treatment. The peak incidence of invasive carcinoma of the vulva occurs in the sixth decade, which may indicate that human papillomavirus (HPV)-related preinvasive disease in the younger population has a lower progression rate. However, the risk of invasive disease cannot be disregarded. This is a case series of complete spontaneous resolution of untreated VIN 3/vulvar carcinoma in situ in 5 healthy women aged 20 to 36 years from a single community gynecologic oncologist practice from 2006 to 2010. Complete spontaneous regression of acute VIN 3/vulvar carcinoma in situ was reported in 6 healthy young women aged 20 to 36 years. New sexual partners were reported in 2 of the 6 patients preceding the onset of vulvar lesions within 6 months. All patients were nonsmokers, healthy without known immunocompromise, and noted the acute onset of vulvar lesions. Vulvar intraepithelial neoplasia 3/vulvar carcinoma in situ was diagnosed on biopsy and confirmed on independent review. All lesions were multifocal in nature. Time to spontaneous regression was 6, 6, 8, 12, 18, and 20 weeks after initial biopsy. No patient received the HPV vaccine. Recurrence has not been noted in any of the patients within the follow-up period of 6 to 60 months. Short-term follow-up with conservative management of acute-onset VIN 3/vulvar carcinoma in situ in this young patient population correlates with similar treatment strategies for HPV-related cervical intraepithelial neoplasia of the cervix and may prevent disfigurement, pain, and complications associated with the current recommended therapeutic modalities. The timing of intervention for VIN 3/vulvar carcinoma in

Photodynamic therapy of Cervical Intraepithelial Neoplasia (CIN) high grade

NASA Astrophysics Data System (ADS)

Carbinatto, Fernanda M.; Inada, Natalia M.; Lombardi, Welington; da Silva, Eduardo V.; Belotto, Renata; Kurachi, Cristina; Bagnato, Vanderlei S.

2016-02-01

Cervical intraepithelial neoplasia (CIN) is the precursor of invasive cervical cancer and associated with human papillomavirus (HPV) infection. Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors. PDT is based on the accumulation of a photosensitizer in target cells that will generate cytotoxic reactive oxygen species upon illumination, inducing the death of abnormal tissue and PDT with less damaging to normal tissues than surgery, radiation, or chemotherapy and seems to be a promising alternative procedure for CIN treatment. The CIN high grades (II and III) presents potential indications for PDT due the success of PDT for CIN low grade treatment. The patients with CIN high grade that were treated with new clinic protocol shows lesion regression to CIN low grade 60 days after the treatment. The new clinical protocol using for treatment of CIN high grade shows great potential to become a public health technique.

Vulval intraepithelial neoplasia and periungual Bowen's disease concordant for mucosal (HPV-34) and epidermodysplasia verruciformis (HPV-21) human papillomavirus types

PubMed Central

Ekeowa-Anderson, A. L.; Harwood, C. A.; Perrett, C. M.; Sahota, A.; Annan, H.; Ran, H.; Leigh, I. M.; Gibbon, K. L.

2008-01-01

Summary Human papillomavirus (HPV) infection is associated with genital malignancy and specific cutaneous malignancies. We report a case of an HPV-associated concurrent vulval intraepithelial neoplasia and periungual Bowen's disease in a young immunocompetent Afro-Caribbean woman with no known risk factors for either disease. HPV genotyping studies detected multiple α and β papillomaviruses with concordance for HPV-34 [a high-risk (HR) mucosal type], and HPV-21 [an epidermodyslasia verruciformis (EV) type] in both vulval and finger tissue. Although the HR-mucosal viruses detected are likely to have a pathogenic role in vulval intraepithelial neoplasia, this is the first report of concordance for EV HPV types in both genital and nongenital skin premalignancies. This case, in the context of accumulating epidemiological and experimental data in cutaneous SCC, raises the question of whether EV HPV may contribute to vulval malignancy, and further study is merited. PMID:17362236

Oral Progestogens Versus Levonorgestrel-Releasing Intrauterine System for Treatment of Endometrial Intraepithelial Neoplasia.

PubMed

Marnach, Mary L; Butler, Kristina A; Henry, Michael R; Hutz, Catherine E; Langstraat, Carrie L; Lohse, Christine M; Casey, Petra M

2017-04-01

Limited therapeutic guidelines exist regarding medical therapy, ideal dosing, duration of therapy, or recommendations for timing of endometrial reassessment for women with endometrial intraepithelial neoplasia (EIN) who desire fertility preservation or who are not optimal surgical candidates. We aimed to determine the effectiveness of oral progestogens (OP) versus the levonorgestrel-releasing intrauterine system (LNG IUS) in the medical treatment of EIN. We retrospectively identified women with EIN at our institution from 2007 through 2014 and compared the outcomes of those treated with OP versus LNG IUS. Among 390 women, 296 were initially treated with OP and 94 with LNG IUS. Baseline characteristics of the patient groups were comparable, except for higher median body mass index in the LNG IUS group versus the OP group (37 kg/m 2 vs. 31 kg/m 2 ; p < 0.001). Among 332 women with follow-up endometrial biopsies (263 OP and 69 LNG IUS), EIN subcategory 1 (benign endometrial hyperplasia) resolved in 83% and 87% of patients, respectively (p = 0.31). Rates of resolution of EIN subcategory 2 (endometrial intraepithelial neoplasia) were also similar between groups (68% vs. 62%; p = 0.82). In women with EIN subcategory 3 (endometrial adenocarcinoma), 22% of those using LNG IUS and one of two women treated with OP had resolution of disease as of last follow-up. OP and LNG IUS offer similar endometrial protection for women with EIN. LNG IUS offers convenience, minimal adverse effects, reversibility, and long-term endometrial protection.

Anal cancer and intraepithelial neoplasia screening: A review

PubMed Central

Leeds, Ira L; Fang, Sandy H

2016-01-01

This review focuses on the early diagnosis of anal cancer and its precursor lesions through routine screening. A number of risk-stratification strategies as well as screening techniques have been suggested, and currently little consensus exists among national societies. Much of the current clinical rationale for the prevention of anal cancer derives from the similar tumor biology of cervical cancer and the successful use of routine screening to identify cervical cancer and its precursors early in the disease process. It is thought that such a strategy of identifying early anal intraepithelial neoplasia will reduce the incidence of invasive anal cancer. The low prevalence of anal cancer in the general population prevents the use of routine screening. However, routine screening of selected populations has been shown to be a more promising strategy. Potential screening modalities include digital anorectal exam, anal Papanicolaou testing, human papilloma virus co-testing, and high-resolution anoscopy. Additional research associating high-grade dysplasia treatment with anal cancer prevention as well as direct comparisons of screening regimens is necessary to develop further anal cancer screening recommendations. PMID:26843912

Intraepithelial and invasive neoplasia of the vulva in association with human papillomavirus infection.

PubMed

Planner, R S; Hobbs, J B

1988-06-01

Colposcopic examination of 335 women with cytologically detected human papillomavirus (HPV) revealed involvement of the cervix in 316 patients (94%), vagina in 276 (82%) and vulva in 148 (44%). A symptom complex of pruritus and superficial dyspareunia was found in 98 of the 148 patients with vulvar infection (66%). Histologic examination revealed HPV-associated vulvar intraepithelial neoplasia (VIN) in 11 of 148 biopsies (7.4%). Follow-up of the patients with HPV infection with or without VIN showed a spontaneous regression rate of 56% but also demonstrated progression to VIN 3 in two patients and to invasive carcinoma of the vulva in one.

Multicentric intraepithelial neoplasia involving the vulva. Clinical features and association with human papillomavirus and herpes simplex virus.

PubMed

Bornstein, J; Kaufman, R H; Adam, E; Adler-Storthz, K

1988-10-15

Sixteen of 46 patients (35%) with Grade 3 vulvar intraepithelial neoplasia (VIN 3) were found to have an additional site of lower genital tract squamous cell neoplasia, primarily in the cervix. The frequency of multicentricity decreased significantly with age. In addition, patients with multicentric disease (involving the vagina and/or cervix in addition to the vulva) had a significantly higher frequency of multifocal disease involving the vulva (involving more than one location on the vulva) and of recurrence than patients without multicentric disease. Human papillomavirus (HPV) DNA was detected by in situ hybridization in 81% of the women with multicentric squamous cell neoplasia. No significant difference was noticed between patients with multicentric and unicentric squamous cell neoplasia in the detection rate of papillomavirus antigen, HPV DNA, the various HPV types, herpes simplex virus Type 2 (HSV2)-related antigen, type-specific antibodies to HSV, and dual HPV and HSV2 infections. These findings suggest that HPV and HSV2, although strongly associated with VIN 3, do not influence the development pattern of squamous cell neoplasia, and that all patients with VIN 3, especially if they are younger than 50 years of age, should be evaluated periodically for additional centers of lower genital tract squamous cell neoplasia.

Phase II Trial of β-All-trans-Retinoic Acid for Cervical Intraepithelial Neoplasia Delivered via a Collagen Sponge and Cervical Cap

PubMed Central

Graham, Vivian; Surwit, Earl S.; Weiner, Sheldon; Meyskens, Frank L.

1986-01-01

Retinoids are effective suppressors of the phenotypic development of cancer in many animal systems, whether the process is initiated by chemical, physical or viral carcinogens. Cases of cervical intraepithelial neoplasia are excellent for studying the effectiveness of retinoids as chemopreventive agents because the process can be closely followed by serial colposcopic and pathologic (cytology or biopsy) means and changes in the condition safely monitored. We have previously conducted a phase I study of trans-retinoic acid (Tretinoin) given topically by a collagen sponge and cervical cap. A dose of 0.372% was selected for phase II trial. We have treated 20 patients with topical retinoic acid, and a complete response with total regression of disease was obtained in 50%. Systemic and cervical side effects were mild and vaginal side effects moderate but tolerable. These results provide a clinical basis for a randomized, double-blind phase III study to definitely answer the question of whether retinoic acid is an effective chemopreventive agent for cervical cancer. ImagesFigure. 1. PMID:3765597

Differentiating between endocervical glandular neoplasia and high grade squamous intraepithelial lesions in endocervical crypts: cytological features in ThinPrep and SurePath cervical cytology samples.

PubMed

Thiryayi, Sakinah A; Marshall, Janet; Rana, Durgesh N

2009-05-01

A recent audit at our institution revealed a higher number of cases diagnosed as endocervical glandular neoplasia on ThinPrep (TP) cervical cytology samples (9 cases) as opposed to SurePath (SP) (1 case), which on histology showed only high-grade cervical intraepithelial neoplasia (CIN) with endocervical crypt involvement (CI). We attempted to ascertain the reasons for this finding by reviewing the available slides of these cases, as well as slides of cases diagnosed as glandular neoplasia on cytology and histology; cases diagnosed as high-grade squamous intraepithelial lesions (HSIL) on cytology which had CIN with CI on histology and cases with mixed glandular and squamous abnormalities diagnosed both cytologically and histologically. Single neoplastic glandular cells and short pseudostratified strips were more prevalent in SP than TP with the cell clusters in glandular neoplasia 3-4 cells thick, in contrast to the dense crowded centre of cell groups in HSIL with CI. The cells at the periphery of groups can be misleading. Cases with HSIL and glandular neoplasia have a combination of the features of each entity in isolation. The diagnosis of glandular neoplasia remains challenging and conversion from conventional to liquid based cervical cytology requires a period of learning and adaptation, which can be facilitated by local audit and review of the cytology slides in cases with a cytology-histology mismatch. (c) 2009 Wiley-Liss, Inc.

Multicolor immunofluorescence reveals that p63- and/or K5-positive progenitor cells contribute to normal breast epithelium and usual ductal hyperplasia but not to low-grade intraepithelial neoplasia of the breast.

PubMed

Boecker, Werner; Stenman, Göran; Schroeder, Tina; Schumacher, Udo; Loening, Thomas; Stahnke, Lisa; Löhnert, Catharina; Siering, Robert Michael; Kuper, Arthur; Samoilova, Vera; Tiemann, Markus; Korsching, Eberhard; Buchwalow, Igor

2017-05-01

We contend that knowledge about the cellular composition of normal breast epithelium is a prerequisite for understanding proliferative breast disease. Against this background, we used multicolor immunofluorescence to study normal breast epithelium and two types of intraepithelial proliferative breast lesion for expression of the p63, basal keratin K5, glandular keratin K8/18, SMA, ER-alpha, and Ki67. We studied eight normal breast epithelium samples, 12 cases of usual ductal hyperplasia, and 33 cases of low-grade intraepithelial neoplasia (9 flat epithelial atypia, 14 low-grade ductal carcinoma in situ and 10 cases of lobular neoplasia). Usual ductal hyperplasia showed striking similarity to normal luminal breast epithelium including p63+ and/or K5+ luminal progenitor cells and the full spectrum of luminal progeny cells. In normal breast epithelium and usual ductal hyperplasia, expression of ER-alpha was associated with lack of expression of the proliferation antigen Ki67. In contrast, we found in both types of low-grade intraepithelial neoplasia robust expression of keratin K8/18 and a positive association between ER-alpha and Ki67 expression. However, these lesions were consistently negative for p63 and/or K5. Our observational study supports the view that usual ductal hyperplasia and low-grade intraepithelial neoplasia are different entities rather than part of a spectrum of the same disease. We propose a new operational model of cell differentiation that may serve to better understand correlations between normal breast epithelium and proliferative breast diseases. From our data we conclude that p63+ and/or K5+ progenitor cells contribute to maintenance of normal epithelium and usual ductal hyperplasia, but not to low-grade intraepithelial neoplasia of the breast.

Development of surrogate endpoint biomarkers for clinical trials of cancer chemopreventive agents: relationships to fundamental properties of preinvasive (intraepithelial) neoplasia.

PubMed

Boone, C W; Kelloff, G J

1994-01-01

The tissue changes offering the greatest immediate potential for development as surrogate endpoint biomarkers (SEBs) to be used in Phase II trials of cancer chemopreventive agents are those derived from the microscopic tissue changes pathologists use to make the diagnosis of preinvasive (intraepithelial) neoplasia. These changes comprise four categories: proliferative index, ploidy, nuclear morphometry (size, shape, texture, and pleomorphism), and nucleolar morphometry (number, size, shape, position, and pleomorphism). Computer-assisted image analysis (CIA) permits dozens of additional morphometric parameters to be developed. Other categories of candidate SEBs are: DNA and chromosomal structural changes associated with genomic instability, activation of oncogenes and inactivation of tumor suppressor genes, structural changes in differentiated molecules, and aberrations of growth factor/receptor structure and function. Self-perpetuating DNA breakage with secondary mutator mutations in genomic stability genes is a major mechanism by which the genomic instability characteristic of neoplasia occurs, and from which stem other basic neoplastic properties, including clonal evolution, along multiple pathways of genetic variation that are stochastically determined, continuously increasing proliferation, rate and extent of phenotypic heterogeneity. SEBs resulting from genomic instability include homogeneously staining regions, double minute chromosomes, micronuclei, dicentrics, gene amplification, loss of heterozygosity, and alterations in chromosome number. Newly developed assays for detecting genomic instability include comparative genomic hybridization using fluorescence in situ hybridization on > 20 micron-thick sections monitored by confocal laser scanning microscopy, assays for microsatellite instability, and restriction landmark genomic scanning. These assays offer promise for detecting the earliest molecular changes of neoplasia in normal-appearing epithelium prior

Diagnostic and Treatment Reproducibility of Cervical Intraepithelial Neoplasia / Squamous Intraepithelial Lesion and Factors Affecting the Diagnosis.

PubMed

Sağlam, Arzu; Usubütün, Alp; Dolgun, Anıl; Mutter, George L; Salman, M Coşkun; Kurtulan, Olcay; Akyol, Aytekin; Özkan, Eylem Akar; Baykara, Sema; Bülbül, Dilek; Calay, Zerrin; Eren, Funda; Gümürdülü, Derya; Haberal, Nihan; Ilvan, Şennur; Karaveli, Şeyda; Koyuncuoğlu, Meral; Müezzinoğlu, Bahar; Müftüoğlu, Kamil Hakan; Özen, Özlem; Özdemir, Necmettin; Peştereli, Elif; Ulukuş, Çağnur; Zekioğlu, Osman

2017-01-01

Inter-observer differences in the diagnosis of HPV related cervical lesions are problematic and response of gynecologists to these diagnostic entities is non-standardized. This study evaluated the diagnostic reproducibility of "cervical intraepithelial neoplasia" (CIN) and "squamous intraepithelial lesion" (SIL) diagnoses. 19 pathologists evaluated 66 cases once using H&E slides and once with immunohistochemical studies (p16, Ki-67 and Pro-ExC). Management response to diagnoses was evaluated amongst 12 gynecologists. Pathologists and gynecologists were also given a questionnaire about how additional information like smear results and age modify diagnosis and management. We show moderate interobserver diagnostic reproducibility amongst pathologists. The overall kappa value was 0.50 and 0.59 using the CIN and SIL classifications respectively. Impact of immunohistochemical evaluation on interpretation of cases differed and there was lack of statistically significant improvement of interobserver diagnostic reproducibility with the addition of immunohistochemistry. We saw that choice of treatment methods amongst gynecologists varied and overall concordance was only fair to moderate. The CIN2 diagnostic category was seen to have the lowest percentage agreement amongst both pathologists and gynecologists. We showed that pathologists had diagnostic "styles" and gynecologists had management "styles". In summary each pathologist had different diagnostic tendencies which were affected not only by histopathology and marker studies, but also by the patient management tendencies of the gynecologist that the pathologist worked with. The two-tiered modified Bethesda system improved diagnostic agreement. We concluded that immunohistochemistry should be used only to resolve problems in select cases and not for every case.

[New histological terminology of vulvar intraepithelial neoplasia].

PubMed

Bergeron, C

2008-01-01

The International Society for the Study of Vulvar Disease (ISSVD) recommends not to use a grading any more and to include in the term vulvar intraepithelial neoplasia (VIN), usual type, the previously called VIN 2 where the nuclear atypia and mitotic figures are confined to the basal half of the epithelium and VIN 3 where nuclear abnormalities and abnormal mitotic figures are present throughout most or all of the thickness of the epithelium. VIN, usual type, is related to a human papillomavirus (HPV) high-risk type infection in most of the cases. The histologic changes previously encompassed within the term VIN 1 will be described as flat condyloma or HPV effect. The less common type of VIN lesion is termed VIN, differentiated type, previously called "high grade" differentiated type or VIN simplex type. This type of VIN is a highly differentiated lesion. The atypia is confined to the basal and parabasal layers of the epithelium, where the cells have abundant cytoplasm and form abortive pearls and the nuclei are relatively uniform in size and contain coarse chromatin and prominent nucleoli. The epithelium does not contain koilocytosis because it is not associated with HPV. It is seen primarily in older women, with a previous history of lichen sclerosus. The diagnosis is often made late in association with keratinising squamous cell carcinomas.

Differentiated intraepithelial neoplasia of the vulva.

PubMed

Mulvany, Nicholas J; Allen, David G

2008-01-01

We present the clinical and pathological findings of 6 women with intraepithelial neoplasia of differentiated or simplex type (DVIN). The mean age was 68 years (range 55-82). One lesion was still in situ, whereas 5 were associated with squamous carcinoma, 4 of well-differentiated keratinizing type and 1 of poorly differentiated spindle-cell type. The invasive depth of the squamous carcinomas ranged from 0.6 to 8 mm and the surgical margins of all of the resection specimens were uninvolved by neoplastic cells. In contrast, DVIN involved the surgical margins in 5 specimens while the remaining specimen had normal surgical margins. In all 6 vulvar specimens, DVIN showed intense immunoreactivity for Ki-67 in the basal and parabasal cells while only 4 specimens showed reactivity for p53. In 5 surgical specimens with DVIN the number of CD1a cells was increased but little if any immunoreactivity could be found amongst the corresponding invasive neoplastic cells. Four squamous carcinomas also showed diffuse p53 reactivity. There was little difference in the pattern of Ki-67 expression between DVIN and squamous carcinoma. For a number of reasons, DVIN present diagnostic difficulty and considerable interobserver variation also exists. Our study suggests that Ki-67 and p16 are useful for distinguishing DVIN and classical VIN 3, whereas p53 and CD1a are useful for distinguishing DVIN and invasive squamous carcinoma. Furthermore, p53 appears to have higher specificity than sensitivity for distinguishing DVIN from normal squamous epithelium.

Frequency of invasive cancer in surgically excised vulvar lesions with intraepithelial neoplasia (VIN 3).

PubMed

Husseinzadeh, N; Recinto, C

1999-04-01

The aim of this study was to determine the frequency of invasive cancer found from specimens removed by surgical excision on patients with diagnosis of VIN 3. Seventy-eight patients with biopsy-proven vulvar intraepithelial neoplasia 3 (VIN 3) were treated by surgical excision. Sixteen patients (20.5%) were found to have invasion in the excised surgical specimen. Superficial invasion was seen in 7 patients (9%), 9 were noted to have >1 mm invasion (11.5%), and 1 patient had in situ Paget's disease (1.3%). Surgical excision should be considered a preferable method in management of patients with VIN 3. Copyright 1999 Academic Press.

Pathologic audit of 164 consecutive cases of vulvar intraepithelial neoplasia.

PubMed

Scurry, James; Campion, Michael; Scurry, Bonnie; Kim, Soo Nyung; Hacker, Neville

2006-04-01

There are 2 types of vulvar intraepithelial neoplasia (VIN): warty-basaloid and differentiated. Differentiated VIN is uncommon and seldom diagnosed prior to carcinoma and, traditionally, is not graded. There are currently 3 grading systems for warty-basaloid VIN: the World Health Organization (WHO) 3 grade system of VIN 1-3, a 2 grade system of low and high grade vulvar intraepithelial lesions, and the revised International Society for the Study of Vulvovaginal Disease (ISSVD) classification which has no grading of VIN. According to the ISSVD, VIN 1 should be abolished and VIN 2 and 3 combined into a single category, simply termed warty-basaloid VIN. To determine the best system for grading warty-basaloid VIN and learn more about differentiated VIN, we reviewed the pathology of 164 consecutive women with VIN. Of these, 134 (82.3%) had warty-basaloid VIN, 29 (18.2%) had differentiated VIN, and 1 had both. Of warty-basaloid VIN cases, 4 had VIN 1, 13 VIN 2, and 118 VIN 3 when graded according to the WHO. All VIN 1 occurred in condylomata acuminata. VIN 2 and 3 were distinguished only by degree of abnormality. Differentiated VIN was diagnosed before SCC in only 7 cases (26.7%). Because the only VIN 1 cases seen were in condylomata acuminata and because VIN 2 and 3 were difficult to distinguish and there appears little clinical reason to do so, our study supports the ISSVD proposal that VIN 1 be abolished and VIN 2 and 3 be combined. There needs to be more clinical awareness of vulvar conditions, so that differentiated VIN is biopsied before cancer has supervened.

A case of usual (basaloid)-type vulvar intraepithelial neoplasia that failed to respond to imiquimod cream: clinical implications.

PubMed

Shiozaki, Takaya; Tabata, Tsutomu; Toriyabe, Kuniaki; Motohashi, Takashi; Kondo, Eiji; Tanida, Kouji; Okugawa, Toshiharu; Sagawa, Norimasa

2011-10-01

The authors report a case of usual-type (basaloid-type) vulvar intraepithelial neoplasia (VIN) 3 that failed to respond to imiquimod cream. A 51-year-old Japanese woman visited her local gynecologist complaining of vulvar itching. Atypical cells were noted in cytology smears, but nine vulvar biopsy specimens showed benign proliferation of epithelial tissue. The patient was placed under careful observation for 8 months, when the vulvar smears once again showed atypical cells and biopsy specimens revealed VIN3. The patient was then referred to our hospital where she was given a diagnosis of VIN 3, basaloid type of usual type. The biopsy specimens were positive for p16 and the lesions were confirmed to be human papilloma virus (HPV)-related. We recommended simple vulvectomy but the patient requested conservative treatment with imiquimod cream. With her written informed consent, we prescribed imiquimod cream to be self-administered 3 times a week. Colposcopy and pap smear test were performed every 2 weeks. Four weeks after the start of treatment, a fingertip-sized papule was detected at the patient's vaginal introitus. By 6 weeks, the lesion had enlarged, and biopsy specimens revealed invasive squamous cell carcinoma. At 7 weeks, we performed simple vulvectomy. The surgical specimen showed stage pT1b keratinizing-type squamous cell carcinoma. HPV-16 DNA was detected in the specimen.

Prior human papillomavirus-16/18 AS04-adjuvanted vaccination prevents recurrent high grade cervical intraepithelial neoplasia after definitive surgical therapy: Post-hoc analysis from a randomized controlled trial.

PubMed

Garland, Suzanne M; Paavonen, Jorma; Jaisamrarn, Unnop; Naud, Paulo; Salmerón, Jorge; Chow, Song-Nan; Apter, Dan; Castellsagué, Xavier; Teixeira, Júlio C; Skinner, S Rachel; Hedrick, James; Limson, Genara; Schwarz, Tino F; Poppe, Willy A J; Bosch, F Xavier; de Carvalho, Newton S; Germar, Maria Julieta V; Peters, Klaus; Del Rosario-Raymundo, M Rowena; Catteau, Grégory; Descamps, Dominique; Struyf, Frank; Lehtinen, Matti; Dubin, Gary

2016-12-15

We evaluated the efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in preventing HPV-related disease after surgery for cervical lesions in a post-hoc analysis of the PApilloma TRIal against Cancer In young Adults (PATRICIA; NCT00122681). Healthy women aged 15-25 years were randomized (1:1) to receive vaccine or control at months 0, 1 and 6 and followed for 4 years. Women were enrolled regardless of their baseline HPV DNA status, HPV-16/18 serostatus, or cytology, but excluded if they had previous or planned colposcopy. The primary and secondary endpoints of PATRICIA have been reported previously; the present post-hoc analysis evaluated efficacy in a subset of women who underwent an excisional procedure for cervical lesions after vaccination. The main outcome was the incidence of subsequent HPV-related cervical intraepithelial neoplasia grade 2 or greater (CIN2+) 60 days or more post-surgery. Other outcomes included the incidence of HPV-related CIN1+, and vulvar or vaginal intraepithelial neoplasia (VIN/VaIN) 60 days or more post-surgery. Of the total vaccinated cohort of 18,644 women (vaccine = 9,319; control = 9,325), 454 (vaccine = 190, control = 264) underwent an excisional procedure during the trial. Efficacy 60 days or more post-surgery for a first lesion, irrespective of HPV DNA results, was 88.2% (95% CI: 14.8, 99.7) against CIN2+ and 42.6% (-21.1, 74.1) against CIN1+. No VIN was reported and one woman in each group had VaIN2+ 60 days or more post-surgery. Women who undergo surgical therapy for cervical lesions after vaccination with the HPV-16/18 vaccine may continue to benefit from vaccination, with a reduced risk of developing subsequent CIN2+. © 2016 UICC.

Biologic behavior of vulvar intraepithelial neoplasia. Histologic and clinical parameters.

PubMed

Barbero, M; Micheletti, L; Preti, M; Valentino, M C; Nicolaci, P; Canní, M; Ghiringhello, B; Borgno, G

1993-02-01

The aim of this study was to evaluate the role by which different factors, such as human papillomavirus (HPV) infection, age, dystrophic alterations, focal nature and size of the lesion, influence the biologic behavior of vulvar intraepithelial neoplasia (VIN). Sixty-nine cases of VIN were investigated (28 VIN 1, 9 VIN 2, 32 VIN 3). Follow-up was possible in 58 cases, with a mean of 31 months; no treatment was given to 3 patients, while 55 were treated either medically or surgically. Eighty-four percent of the patients were cured, recurrences were found in 11%, and 5% of the patients showed progression of the disease to carcinoma. The ratio between medical and surgical treatment was the same among the cured, recurred and progressed groups of patients. No differences with regard to focal nature of the lesion, presence of HPV infection or dystrophic alterations were observed between the three groups of patients. Only the mean age was higher in patients who showed progression of the lesion to carcinoma.

Targeting Human Papillomavirus to Reduce the Burden of Cervical, Vulvar and Vaginal Cancer and Pre-Invasive Neoplasia: Establishing the Baseline for Surveillance

PubMed Central

Nygård, Mari; Hansen, Bo Terning; Dillner, Joakim; Munk, Christian; Oddsson, Kristján; Tryggvadottir, Laufey; Hortlund, Maria; Liaw, Kai-Li; Dasbach, Erik J.; Kjær, Susanne Krüger

2014-01-01

Background Infection with high-risk human papillomavirus (HPV) is causally related to cervical, vulvar and vaginal pre-invasive neoplasias and cancers. Highly effective vaccines against HPV types 16/18 have been available since 2006, and are currently used in many countries in combination with cervical cancer screening to control the burden of cervical cancer. We estimated the overall and age-specific incidence rate (IR) of cervical, vulvar and vaginal cancer and pre-invasive neoplasia in Denmark, Iceland, Norway and Sweden in 2004–2006, prior to the availability of HPV vaccines, in order to establish a baseline for surveillance. We also estimated the population attributable fraction to determine roughly the expected effect of HPV16/18 vaccination on the incidence of these diseases. Methods Information on incident cervical, vulvar and vaginal cancers and high-grade pre-invasive neoplasias was obtained from high-quality national population-based registries. A literature review was conducted to define the fraction of these lesions attributable to HPV16/18, i.e., those that could be prevented by HPV vaccination. Results Among the four countries, the age-standardised IR/105 of cervical, vaginal and vulvar cancer ranged from 8.4–13.8, 1.3–3.1 and 0.2–0.6, respectively. The risk for cervical cancer was highest in women aged 30–39, while vulvar and vaginal cancers were most common in women aged 70+. Age-standardised IR/105 of cervical, vulvar and vaginal pre-invasive neoplasia ranged between 138.8−183.2, 2.5−8.8 and 0.5−1.3, respectively. Women aged 20−29 had the highest risk for cervical pre-invasive neoplasia, while vulvar and vaginal pre-invasive neoplasia peaked in women aged 40−49 and 60−69, respectively. Over 50% of the observed 47,820 incident invasive and pre-invasive cancer cases in 2004−2006 can be attributed to HPV16/18. Conclusion In the four countries, vaccination against HPV 16/18 could prevent approximately 8500 cases of

Prognostic scores after surgical treatment for cervical intraepithelial neoplasia: a proposed model and possible implications for post-operative follow-up.

PubMed

Andrade, Carlos E M C; Scapulatempo-Neto, Cristovam; Longatto-Filho, Adhemar; Vieira, Marcelo A; Tsunoda, Audrey T; Da Silva, Ismael D C G; Fregnani, José Humberto T G

2014-09-01

To develop a prognostic model for women who underwent surgical treatment for cervical intraepithelial neoplasia. Cohort study. Patient inclusion and follow-up occurred retrospectively and prospectively. Barretos Cancer Hospital, Barretos, São Paulo, Brazil. Women (n = 242) diagnosed with cervical intraepithelial neoplasia who were submitted to conization. Immediately prior to surgical treatment, a cervical cytology sample was collected from each individual included in the study by endocervical brushing and stored in a preservative solution with methanol. A human papilloma virus-DNA test was conducted using an aliquot of the endocervical brushings. The surgical specimens were subjected to immunohistochemical analysis of p16 (immunohistochemical analysis 4a) protein expression. Two-year disease-free survival rates calculated for each study variable. Identified variables in the multivariate Cox model were used for elaboration of prognostic scores. Variables associated with outcome included age (p = 0.033), tobacco use (p < 0.001), final histopathological diagnosis (p = 0.007), surgical margins (p < 0.001), high-risk human papilloma virus status (p = 0.008), human papilloma virus-16 status (p < 0.001) and immunoexpression of p16 in the cytoplasm (p = 0.049). By the Cox model, independent risk factors for disease recurrence/persistence were: tobacco use (hazard risk = 3.0; 95% confidence interval 1.6-5.6), positive surgical margins (hazard risk = 3.2; 95% confidence interval 1.6-6.1), human papilloma virus-16 (hazard risk = 3.3; 95% confidence interval 1.6-6.9) and age over 45 years (hazard risk = 2.7; 95% confidence interval 1.1-6.6). Establishment of a prognostic score can represent a valuable tool for determining the risk of cervical intraepithelial neoplasia recurrence after conization. The use of clinical (age and tobacco use), pathological (surgical margins) and molecular (human papilloma virus-16 genotyping) factors can facilitate more

Medical Devices; Hematology and Pathology Devices; Classification of a Cervical Intraepithelial Neoplasia Test System. Final order.

PubMed

2018-01-03

The Food and Drug Administration (FDA or we) is classifying the cervical intraepithelial neoplasia (CIN) test system into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the CIN test system's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

High-resolution anoscopy or expectant management for anal intraepithelial neoplasia for the prevention of anal cancer: is there really a difference?

PubMed

Crawshaw, Benjamin P; Russ, Andrew J; Stein, Sharon L; Reynolds, Harry L; Marderstein, Eric L; Delaney, Conor P; Champagne, Bradley J

2015-01-01

High-resolution anoscopy has been shown to improve identification of anal intraepithelial neoplasia but a reduction in progression to anal squamous-cell cancer has not been substantiated when serial high-resolution anoscopy is compared with traditional expectant management. The aim of this study was to compare high-resolution anoscopy versus expectant management for the surveillance of anal intraepithelial neoplasia and the prevention of anal cancer. This is a retrospective review of all patients who presented with anal squamous dysplasia, positive anal Pap smears, or anal squamous-cell cancer from 2007 to 2013. This study was performed in the colorectal department of a university-affiliated, tertiary care hospital. Included patients had biopsy-proven anal intraepithelial neoplasia from 2007 to 2013. Patients were treated with high-resolution anoscopy with ablation or standard anoscopy with ablation. Both groups were treated with imiquimod and followed every 6 months indefinitely. The incidence of anal squamous-cell cancer in each group was the primary end point. From 2007 to 2013, 424 patients with anal squamous dysplasia were seen in the clinic (high-resolution anoscopy, 220; expectant management, 204). Three patients (high-resolution anoscopy, 1; expectant management, 2) progressed to anal squamous-cell cancer; 2 were noncompliant with follow-up and with HIV treatment, and the third was allergic to imiquimod and refused to take topical 5-fluorouracil. The 5-year progression rate was 6.0% (95% CI, 1.5-24.6) for expectant management and 4.5% (95% CI, 0.7-30.8) for high-resolution anoscopy (p = 0.37). This was a retrospective review. There is potential for selection and referral bias. Because of the rarity of the outcome, the study may be underpowered. Patients with squamous-cell dysplasia followed with expectant management or high-resolution anoscopy rarely develop squamous-cell cancer if they are compliant with the protocol. The cost, morbidity, and value of high

Vulvar Intraepithelial Neoplasia 3 in Women Less Than 35 Years

PubMed Central

Kesterson, Joshua P.; Lele, Shashikant

2016-01-01

Objective To examine the outcome of women diagnosed with vulvar intraepithelial neoplasia (VIN) 3 at less than 35 years. Materials and Methods All cases of VIN 3 treated in women less than 35 years treated at Roswell Park Cancer Institute between January 1973 and January 2008 were reviewed. Medical records were reviewed for year of diagnosis, treatment modality, recurrence and/or progression, associated medical conditions, history of genital condyloma, smoking status, history of cervical pathology, and treatment. Results Thirty-one women were identified. The mean age at diagnosis was 29 years. Smoking status was available in 28 patients, of which 82% (23/28) were current or former smokers. Eighty-one percent (25/31) of the women had cervical disease. Fifty-two percent (16/31) had a history of genital condyloma. Ten of the 31 women (32%) were diagnosed with persistence or recurrence of VIN 3. Three women (9.7%) progressed to invasive carcinoma. Conclusions Women diagnosed with VIN 3 at less than 35 years are at risk for persistence and/or recurrence of their disease as well as progression to carcinoma, warranting frequent and prolonged follow-up with liberal utilization of directed biopsies of suspicious lesions. PMID:27942201

Vulvar Intraepithelial Neoplasia 3 in Women Less Than 35 Years.

PubMed

Kesterson, Joshua P; Lele, Shashikant

2009-10-01

To examine the outcome of women diagnosed with vulvar intraepithelial neoplasia (VIN) 3 at less than 35 years. All cases of VIN 3 treated in women less than 35 years treated at Roswell Park Cancer Institute between January 1973 and January 2008 were reviewed. Medical records were reviewed for year of diagnosis, treatment modality, recurrence and/or progression, associated medical conditions, history of genital condyloma, smoking status, history of cervical pathology, and treatment. Thirty-one women were identified. The mean age at diagnosis was 29 years. Smoking status was available in 28 patients, of which 82% (23/28) were current or former smokers. Eighty-one percent (25/31) of the women had cervical disease. Fifty-two percent (16/31) had a history of genital condyloma. Ten of the 31 women (32%) were diagnosed with persistence or recurrence of VIN 3. Three women (9.7%) progressed to invasive carcinoma. Women diagnosed with VIN 3 at less than 35 years are at risk for persistence and/or recurrence of their disease as well as progression to carcinoma, warranting frequent and prolonged follow-up with liberal utilization of directed biopsies of suspicious lesions.

Reconstituting development of pancreatic intraepithelial neoplasia from primary human pancreas duct cells

PubMed Central

Lee, Jonghyeob; Snyder, Emily R.; Liu, Yinghua; Gu, Xueying; Wang, Jing; Flowers, Brittany M.; Kim, Yoo Jung; Park, Sangbin; Szot, Gregory L.; Hruban, Ralph H.; Longacre, Teri A.; Kim, Seung K.

2017-01-01

Development of systems that reconstitute hallmark features of human pancreatic intraepithelial neoplasia (PanINs), the precursor to pancreatic ductal adenocarcinoma, could generate new strategies for early diagnosis and intervention. However, human cell-based PanIN models with defined mutations are unavailable. Here, we report that genetic modification of primary human pancreatic cells leads to development of lesions resembling native human PanINs. Primary human pancreas duct cells harbouring oncogenic KRAS and induced mutations in CDKN2A, SMAD4 and TP53 expand in vitro as epithelial spheres. After pancreatic transplantation, mutant clones form lesions histologically similar to native PanINs, including prominent stromal responses. Gene expression profiling reveals molecular similarities of mutant clones with native PanINs, and identifies potential PanIN biomarker candidates including Neuromedin U, a circulating peptide hormone. Prospective reconstitution of human PanIN development from primary cells provides experimental opportunities to investigate pancreas cancer development, progression and early-stage detection. PMID:28272465

[Local treatment of cervical intraepithelial neoplasia with a 5 percent fluorouracil ointment].

PubMed

Barten, G

1987-01-01

The results of treatment of histologically proven cervical intraepithelial neoplasia (CIN) in 10 women are described. Two of them had CIN I and 8 CIN III. All patients had a application of 5 g 5 per cent 5-fluorouracil cream in a cervical cup daily over a period of 12 hours for one week. All 10 patients have been examined colposcopically, cytological and by biopsy following therapy. In 8 women cone biopsie were done 6-12 months afterwards for having a final diagnosis 2 patients having CIN I pretherapeutically were follow up for 16 months with cytology, colposcopy and punch biopsy. In 6 cases we found better findings (Twice complete healing, twice only CIN I and twice CIN II as residues). In 4 cases severe dysplasia and carcinoma in situ could be found in endocervix. Based on these results were recommended more (not only one) treatment cycles for local efficient chemotherapy using 5 per cent 5-fluorouracil cream.

Hyperspectral wide gap second derivative analysis for in vivo detection of cervical intraepithelial neoplasia

NASA Astrophysics Data System (ADS)

Zheng, Wenli; Wang, Chaojian; Chang, Shufang; Zhang, Shiwu; Xu, Ronald X.

2015-12-01

Hyperspectral reflectance imaging technique has been used for in vivo detection of cervical intraepithelial neoplasia. However, the clinical outcome of this technique is suboptimal owing to multiple limitations such as nonuniform illumination, high-cost and bulky setup, and time-consuming data acquisition and processing. To overcome these limitations, we acquired the hyperspectral data cube in a wavelength ranging from 600 to 800 nm and processed it by a wide gap second derivative analysis method. This method effectively reduced the image artifacts caused by nonuniform illumination and background absorption. Furthermore, with second derivative analysis, only three specific wavelengths (620, 696, and 772 nm) are needed for tissue classification with optimal separability. Clinical feasibility of the proposed image analysis and classification method was tested in a clinical trial where cervical hyperspectral images from three patients were used for classification analysis. Our proposed method successfully classified the cervix tissue into three categories of normal, inflammation and high-grade lesion. These classification results were coincident with those by an experienced gynecology oncologist after applying acetic acid. Our preliminary clinical study has demonstrated the technical feasibility for in vivo and noninvasive detection of cervical neoplasia without acetic acid. Further clinical research is needed in order to establish a large-scale diagnostic database and optimize the tissue classification technique.

Hyperspectral wide gap second derivative analysis for in vivo detection of cervical intraepithelial neoplasia.

PubMed

Zheng, Wenli; Wang, Chaojian; Chang, Shufang; Zhang, Shiwu; Xu, Ronald X

2015-12-01

Hyperspectral reflectance imaging technique has been used for in vivo detection of cervical intraepithelial neoplasia. However, the clinical outcome of this technique is suboptimal owing to multiple limitations such as nonuniform illumination, high-cost and bulky setup, and time-consuming data acquisition and processing. To overcome these limitations, we acquired the hyperspectral data cube in a wavelength ranging from 600 to 800 nm and processed it by a wide gap second derivative analysis method. This method effectively reduced the image artifacts caused by nonuniform illumination and background absorption. Furthermore, with second derivative analysis, only three specific wavelengths (620, 696, and 772 nm) are needed for tissue classification with optimal separability. Clinical feasibility of the proposed image analysis and classification method was tested in a clinical trial where cervical hyperspectral images from three patients were used for classification analysis. Our proposed method successfully classified the cervix tissue into three categories of normal, inflammation and high-grade lesion. These classification results were coincident with those by an experienced gynecology oncologist after applying acetic acid. Our preliminary clinical study has demonstrated the technical feasibility for in vivo and noninvasive detection of cervical neoplasia without acetic acid. Further clinical research is needed in order to establish a large-scale diagnostic database and optimize the tissue classification technique.

Self-administered topical imiquimod treatment of vulvar intraepithelial neoplasia. A report of four cases.

PubMed

Davis, G; Wentworth, J; Richard, J

2000-08-01

Vulvar intraepithelial neoplasia (VIN) generally can be classified into viral and nonviral etiologies. The histopathologic diagnosis is often separable into basaloid and warty types. A large percentage of VIN lesions have been shown to harbor human papillomavirus (HPV), principally type 16. Imiquimod, an immune response modifier, has been shown to be safe and effective for the treatment of external and perianal genital warts caused by HPV. Four cases occurred of clinical and histopathologically diagnosed viral VIN 3. An imiquimod treatment protocol, previously used in a study of this drug for the treatment of external genital warts, was followed. Imiquimod 5% cream was patient applied three times per week until all lesions cleared, for a maximum of 16 weeks. Imiquimod may be an effective treatment modality for viral VIN 3 in the future.

Association between aerobic vaginitis, bacterial vaginosis and squamous intraepithelial lesion of low grade.

PubMed

Jahic, Mahira; Mulavdic, Mirsada; Hadzimehmedovic, Azra; Jahic, Elmir

2013-01-01

To determine frequency of HPV infection, aerobic vaginitis and bacterial vaginosis in respondents with squamous intraepithelial lesion of lower grade comparing to respondents with normal PAP test results. Prospective research of 100 respondents has been conducted at University-Clinic Center Tuzla and Gynecology and Obstetrics Department at Primary Health Care Center Tuzla in period from May 2011 untill January 2012. Examination program included: anamnesis, clinical gynecological examination, HPV typization, microbiological examination of vaginal and cervical smear and PAP test. High risk HPV group has been found more frequently among the respondents with LG SIL 46% (23) than in those with normal PAP result 14% (7) p < 0.05. Aerobic vaginitis has been found in the respondents with LG SIL in 28% (14) and there is statistically significant difference of this vaginitis comparing to the respondents with normal PAP result (p < 0.05). Bacterial vaginosis has been found in 12% (6) of the respondents with LG SIL and in 4% (2) of those with normal PAP result which is not statistically significant. In women with LG SIL and aerobic vaginitis in 9 cases E. coli has been isolated, in 4 E. faecalis and in 1 Staphylococcus aureus, while in women with normal PAP test results 3 cases of E.coli have been isolated. Examining changes in pH value of vaginal environment, higher measured values have been found in the respondents with LG SIL- 5.26 while in the respondents with normal PAP test result was 4.94 (p < 0.05). There is also statistically significant increase in the number of leukocytes in the respondents with LG SIL in relation to those with normal result. In women with LG SIL aerobic vaginitis is very common but is not an indicator of HPV infection. An adequate treatment of aerobic vaginitis would decrease the frequency of LG SIL and number of precancerous lesions which may

Age-related changes in pre- and post-conization HPV genotype distribution among women with high-grade cervical intraepithelial neoplasia.

PubMed

Giannella, Luca; Fodero, Cristina; Boselli, Fausto; Rubino, Teresa; Mfuta, Kabala; Prandi, Sonia

2017-04-01

To assess the effect of age on pre- and post-conization HPV genotype distribution. The present retrospective observational study included consecutive women with high-grade cervical intraepithelial neoplasia who underwent conization at the Cervical Cancer Screening Centre of Reggio Emilia, Italy, and University Hospital of Modena, Italy, between February 1, 2012, and October 31, 2014. Pre-conization and 6-month post-conization HPV genotyping results were compared between four age groups (<30, 30-39, 40-49, and ≥50 years) and age-related changes in the HPV genotypes present were evaluated. There were 162 patients included. The lowest occurrence of pre-conization high-risk and probable high-risk HPV genotypes was observed among patients aged at least 50 years when compared with younger patients (P=0.017). Conversely, women aged at least 50 years exhibited the highest level of post-conization high-risk and probable high-risk HPV genotypes (P=0.043). Additionally, an increasing incidence of recording identical pre- and post-conization HPV genotypes was associated with increasing age (P=0.024), as was increasing post-treatment recurrence of cervical intraepithelial neoplasia grade 2+ (P=0.030). The presence of high-risk and probable high-risk HPV genotypes was lowest among older patients before conization and was highest among these patients post-conization; post-treatment HPV clearance decreased with age and increasing age could be a risk factor for post-conization recurrence. © 2017 International Federation of Gynecology and Obstetrics.

Number of fragments, margin status and thermal artifacts of conized specimens from LLETZ surgery to treat cervical intraepithelial neoplasia.

PubMed

Bittencourt, Dulcimary Dias; Zanine, Rita Maira; Sebastião, Ana Martins; Taha, Nabiha Saadi; Speck, Neila Góis; Ribalta, Julisa Chamorro Lascasas

2012-01-01

Large loop excision of the transformation zone (LLETZ) is a nontraumatic cut and coagulation method with several advantages, but it induces thermal artifacts in the cut region. The aim here was to assess the correlations of age, number of fragments, lesion grade and degree of thermal artifacts with margin quality in conized specimens from LLETZ for cervical intraepithelial neoplasia (CIN). Cross-sectional study at Universidade Federal de São Paulo (Unifesp). The records and histopathology findings of 118 women who underwent LLETZ between 1999 and 2007 were reviewed. Age, number of fragments, lesion grade, degree of thermal artifacts and margin quality were assessed. The patients' mean age was 27.14 years; 63.6% had been diagnosed with CIN II and 36.4% with CIN III. The lesion was removed as a single fragment in 79.6% of the cases. The margins were free from intraepithelial neoplasia in 85.6% and compromised in the endocervical margin in 6.8%. Fragment damage due to artifacts occurred in 2.5%. Severe artifacts occurred in 22.8%. Women aged 30 years or over presented more cases of CIN III (P < 0.0004). Neoplastic compromising of surgical margins and severe artifacts occurred more often in cases in which two or more fragments were removed, and in patients aged 30 years or over. CIN III in women aged 30 or over, when removed in two or more fragments during LLETZ, presented a greater number of compromised margins and greater severity of thermal artifacts.

Increased incidence of cervical intraepithelial neoplasia in young women in the Mitte district, Berlin, Germany.

PubMed

Blohmer, J U; Schmalisch, G; Klette, I; Grineisen, Y; Kohls, A; Guski, H; Lichtenegger, W

1999-01-01

To investigate whether the incidence of cervical intraepithelial neoplasia (CIN), in particular of high grade CIN, increased in Berlin during the period 1970-1989 and whether the ages of women with CIN had decreased. In the former German Democratic Republic, which had a highly centralized public health system, all gynecologic operations performed on women living in the Mitte district of Berlin were carried out during the period 1970-1989 (when the Berlin Wall fell) in the gynecologic clinic of the Charité Hospital. The incidence of all CIN increased from year to year over the observation period: 0.04% (1970-1971), 0.10% (1980-1981), 0.39% (1988-1989). There was a particularly high increase in the incidence of high grade intraepithelial neoplasms (CIN 3): 0.016% (1970-1971), 0.056% (1980-1981), 0.25% (1988-1989). With a virtually unchanged age distribution for women in the Mitte district of Berlin, the median age of women with CIN 3 decreased significantly from 1970 to 1989, from 39.5 (1970) to 33 (1989) (P < .001). The increase in the incidence of CIN, especially of high grade CIN, as well as the reduction in age for onset of the disease, makes high participation in screening necessary, above all among young women.

Mutational spectrum of intraepithelial neoplasia in pancreatic heterotopia.

PubMed

Ma, Changqing; Gocke, Christopher D; Hruban, Ralph H; Belchis, Deborah A

2016-02-01

Heterotopic pancreatic parenchyma recapitulates the normal pancreas in extrapancreatic locations and, on rare occasions, can even give rise to pancreatic adenocarcinoma. The genetic signatures of pancreatic adenocarcinoma and its precursor lesions are well characterized. We explored the genetic alterations in precursor lesions (intraductal papillary mucinous neoplasms [IPMN], pancreatic intraepithelial neoplasia [PanIN]) in patients with pancreatic heterotopias but without concomitant pancreatic ductal adenocarcinomas. This allowed us to determine whether the stereotypical dysplasia--infiltrating carcinoma sequence also occurs in these extrapancreatic foci. Seven cases of heterotopic pancreas with ductal precursor lesions were identified. These included 2 IPMNs with focal high-grade dysplasia and 5 PanINs with low- to moderate-grade dysplasia (PanIN grades 1-2). Neoplastic epithelium was microdissected and genomic DNA was extracted. Sequencing of commonly mutated hotspots (KRAS, TP53, CDKN2A, SMAD4, BRAF, and GNAS) in pancreatic ductal adenocarcinoma and its precursor lesions was performed. Both IPMNs were found to have KRAS codon 12 mutations. The identification of KRAS mutations suggests a genetic pathway shared with IPMN of the pancreas. No mutations were identified in our heterotopic PanINs. One of the possible mechanisms for the development of dysplasia in these lesions is field effect. At the time of these resections, there was no clinical or pathologic evidence of a prior or concomitant pancreatic lesion. However, a clinically undetectable lesion is theoretically possible. Therefore, although a field effect cannot be excluded, there was no evidence for it in this study. Copyright © 2015 Elsevier Inc. All rights reserved.

Laboratory management of cervical intraepithelial neoplasia: proposing a new paradigm.

PubMed

Herfs, Michael; Crum, Christopher P

2013-03-01

Since the discovery of human papillomavirus (HPV) type 16 in early 80s, the link between HPV and cervical cancer has been established with certainty, a function of the discovery and cloning of a range of HPV types associated with both cancer precursors (cervical intraepithelial neoplasia or CIN) and carcinomas and extensive epidemiologic, clinical, pathologic, and experimental data. These accumulated results have culminated in new paradigms of cancer prevention through screening and triage. Despite this, the management of women with CIN is still suboptimal and the overtreatment of these conditions still occurs, largely due to the lack of clarity regarding which precancerous lesions are most likely to progress in grade. Recently, a discrete population of cuboidal cells was discovered at the cervical squamocolumnar junction, the anatomic site where the large majority of HPV-related (pre)neoplastic lesions develop. These cells seem to be embryonic in nature and participate both in benign metaplasias and the initial phase of precancer development. This review summarizes the historical evolution of precursor management, assesses the potential role of this and other discoveries in segregating lower from higher-risk precursors, and examines their potential impact on the management of women with real or potential cervical cancer precursors.

Phenotypic relationships of prostatic intraepithelial neoplasia to invasive prostatic carcinoma.

PubMed Central

Nagle, R. B.; Brawer, M. K.; Kittelson, J.; Clark, V.

1991-01-01

Thirty-one snap-frozen human prostate specimens containing examples of benign hyperplasia, prostatic intraepithelial neoplasia (PIN), and invasive carcinoma were analyzed using a panel of 24 antibodies and one lectin. Twenty-seven additional routinely processed radical prostatectomy specimens were studied using selected probes known to work on formalin-fixed paraffin-embedded material. Three probes, anticytokeratin KA4, anti-vimentin V9, and the lectin from Ulex europaeus (UEA-1), demonstrated phenotypic similarities between PIN and invasive carcinoma. Whereas the luminal cells of normal or hyperplastic prostatic epithelium are minimally reactive with KA4 (4%) or UEA-1 (0%) and strongly reactive with anti-vimentin (91%), both the PIN and invasive carcinoma are reactive with KA4 (89% and 93%, respectively) and UEA-1 (96% and 93%, respectively) and minimally reactive with anti-vimentin (15% and 0%, respectively). The increased KA4 staining was shown to be in part due to detection of cytokeratin 19, by using cytokeratin-19-specific antibodies, 4.62 and LP2K. The reasons for the increased expression of this cytokeratin and the decreased expression of vimentin are unclear but seem to indicate a phenotypic relationship between the PIN lesions and invasive carcinoma. Images Figure 4 Figure 1 Figure 2 Figure 3 PMID:1987760

Squamous vulvar intraepithelial neoplasia: 2004 modified terminology, ISSVD Vulvar Oncology Subcommittee.

PubMed

Sideri, Mario; Jones, Ronald W; Wilkinson, Edward J; Preti, Mario; Heller, Debra S; Scurry, James; Haefner, Hope; Neill, Sallie

2005-11-01

In the current classification, squamous vulvar intraepithelial neoplasia (VIN) is categorized as VIN 1, 2 and 3 according to the degree of abnormality. There is neither evidence that the VIN 1-3 morphologic spectrum reflects a biologic continuum nor that VIN 1 is a cancer precursor. The VIN 2 and 3 category includes 2 types of lesion, which differ in morphology, biology and clinical features. VIN, usual type (warty, basaloid and mixed), is HPV related in most cases. Invasive squamous carcinomas of warty or basaloid type is associated with VIN, usual type. VIN, differentiated type, is seen particularly in older women with lichen sclerosus and/or squamous cell hyperplasia in some cases. Neither VIN, differentiated type, nor associated keratinizing squamous cell carcinoma is HPV related. The term VIN should apply only to histologically high grade squamous lesions (former terms, VIN 2 and VIN 3 and differentiated VIN 3). The term VIN 1 will no longer be used. Two categories should describe squamous VIN: VIN, usual type (encompassing former VIN 2 and 3 of warty, basaloid and mixed types) and VIN, differentiated type (VIN 3, differentiated type).

Differentiating vulvar intraepithelial neoplasia from nonneoplastic epithelial disorders. The toluidine blue test.

PubMed

Joura, E A; Zeisler, H; Lösch, A; Sator, M O; Müllauer-Ertl, S

1998-08-01

To determine the effectiveness of the toluidine blue test in the differentiation of vulvar intraepithelial neoplasia (VIN) and nonneoplastic epithelial disorders (NNEDs). This retrospective clinical study included all women with VIN (n = 24) and NNED (n = 72) referred to a vulvar clinic at a university hospital during a two-year period. Vulvoscopy, staining of vulvar epithelium with 1% toluidine blue and punch biopsy were performed. Vulvar epithelium demonstrated toluidine blue staining in 100% of the patients with VIN 3, in 83% of women with VIN 1-2, in 50% of the women with squamous cell hyperplasia and in 10% of the women with lichen sclerosus. The differences in staining between the groups were statistically significant (P < .001). The sensitivity of toluidine blue staining for the detection of VIN was 92%; the negative predictive value 96% in teh investigated cohort. The specificity for strong staining was 88%. The toluidine blue test is an inexpensive and reliable method of separating VIN from hyperplastic NNED areas and choosing a biopsy site on the vulva.

The effects of 5% imiquimod cream on high-grade vulval intraepithelial neoplasia.

PubMed

Todd, Richard W; Etherington, Ian J; Luesley, David M

2002-04-01

The aim of this study was to investigate the effects of topical 5% Imiquimod (3M Pharmaceuticals, St. Paul, Minnessota) on high-grade vulval intraepithelial neoplasia (VIN). A prospective uncontrolled observational study was performed. Fifteen patients with histologically confirmed VIN 3 were asked to self-administer 5% Imiquimod cream to their vulval lesions up to three times weekly for 16 weeks. Review was conducted at 1, 2, 3, 4, 6, and 9 months postrecruitment. Lesions were photodocumented and at 4 months any areas demonstrating a clinical response were biopsied. Of 15 patients recruited, 4 demonstrated a clinical improvement in their disease, 3 of whom had negative biopsies posttreatment. Local side effects limited the frequency of application such that 7 patients applied the cream once weekly, 6 twice weekly, and 2 three times weekly. 5% Imiquimod cream appears to have an effect when used on high-grade VIN. The frequency of application was limited by local side effects which may have reduced the clinical responses seen. Measures to alleviate local side effects may allow more aggressive use of Imiquimod and lead to improved responses.

Treatment of bowenoid and basaloid vulvar intraepithelial neoplasia 2/3 with imiquimod 5% cream.

PubMed

Marchitelli, Claudia; Secco, Graciela; Perrotta, Myriam; Lugones, Leonor; Pesce, Romina; Testa, Roberto

2004-11-01

To evaluate the effectiveness and safety of imiquimod 5% for the treatment of bowenoid and basaloid vulvar intraepithelial neoplasia (VIN) and to evaluate recurrences following treatment. Eight patients <55 years old (range, 32-51; mean, 39.7), with bowenoid or basaloid VIN 2/3 diagnosed by biopsy were treated with imiquimod 5%. Women with other types of intraepithelial neoplasia of the lower genital tract, immunosuppressed women, pregnant women and women with other types of vulvar pathology were excluded. Two patients previously treated for VIN 3 (surgical resection, resection by loop electrosurgical excision procedure) had recurrences. Patients applied imiquimod cream 3 times a week until total clearance of the lesions or up to a maximum of 16 weeks. Responses were categorized as total when there was no colposcopic evidence of a lesion, partial when the lesion area diminished >50% and progressive when there was an increase in the lesion area. A biopsy was performed at the end of treatment. Follow-up was carried out monthly (10-30 months). Total clearance of lesions was observed in 6 patients after 10-16 weeks. Two patients had a partial response (1 with 75% and the other with 50% reduction of the lesions). Posttreatment histopathology showed the absence of precancerous lesions in 7 patients (87.5%). Biopsy was positive for VIN 3 (12.5%) only in the patient showing a clinical response of 50%. Of the 7 patients with biopsies negative for VIN, 2 (25%) were positive for viral infection; 1 gave a negative reading after 2 months after treatment, and the other 1 remained positive for human papillomavirus. The patient with persistent VIN received surgical treatment. The side effects were as follows: erythema in 8 patients (100%), erosions in 1 patient (12.5%) and edema in 1 patient (12.5%). No relapses occurred after treatment during 10-30 months of follow-up. In this initial series, imiquimod proved to be effective for the treatment of bowenoid and basaloid VIN 2/3 in a

Anal cytology as a predictor of anal intraepithelial neoplasia in HIV-positive men and women.

PubMed

Betancourt, Eve M; Wahbah, Mary M; Been, Laura C; Chiao, Elizabeth Y; Citron, Deborah R; Laucirica, Rodolfo

2013-08-01

Human immunodeficiency virus (HIV)-infected individuals have increased risk of anal intraepithelial neoplasia (AIN) and squamous cell carcinoma (SCC). Cytologic screening is invaluable in the detection of cervical neoplasia, therefore many clinicians have adopted anal cytology as part of anal cancer screening in patients at high-risk for anal neoplasia. The purpose of this study is to determine whether anal cytology is a valuable screening test for identifying AIN in HIV+ patients. The cohort included 228 HIV+ patients who underwent anal cancer screening with collection of 318 anal cytology specimens between January 2006 and December 2009. Of this group, 74 (32.5%) patients had associated anal biopsies within a 6-month period, with a total of 89 comparison cases. The anal cytology samples were classified using the 2001 Bethesda System terminology. The sensitivity of anal cytology in detecting ASC-US, AIN 1-3 or SCC was 93%. Cytology was 88% sensitive for detecting low-grade AIN (AIN 1), but only 20% sensitive for detecting high-grade AIN (AIN 2-3) or SCC. Atypical squamous cells of undetermined significance cases were distributed evenly between low- and high-grade AIN, with two cases having normal histology. Only six cases had negative cytology, all of which were associated with AIN on biopsy, for a false negative rate of 7%. Anal cytology is a good predictor of AIN, as confirmed by the high degree of sensitivity. However, there is poor correlation between the cytological and histological grade of AIN. Cytology underestimates the grade of dysplasia compared to the corresponding biopsy. Copyright © 2012 Wiley Periodicals, Inc., a Wiley company.

Treatment failure in patients with HPV 16-induced vulvar intraepithelial neoplasia: understanding different clinical responses to immunotherapy.

PubMed

van Esch, Edith M G; Welters, Marij J P; Jordanova, Ekaterina S; Trimbos, J Baptist M Z; van der Burg, Sjoerd H; van Poelgeest, Mariëtte I E

2012-07-01

Failure of the immune system to launch a strong and effective immune response to high-risk HPV is related to viral persistence and the development of anogenital (pre)malignant lesions such as vulvar intraepithelial neoplasia (VIN). Different forms of immunotherapy, aimed at overcoming the inertia of the immune system, have been developed and met with clinical success. Unfortunately these, in principal successful, therapeutic approaches also fail to induce clinical responses in a substantial number of cases. In this review, the authors summarize the traits of the immune response to HPV in healthy individuals and in patients with HPV-induced neoplasia. The potential mechanisms involved in the escape of HPV-induced lesions from the immune system indicate gaps in our knowledge. Finally, the interaction between the immune system and VIN is discussed with a special focus on the different forms of immunotherapy applied to treat VIN and the potential causes of therapy failure. The authors conclude that there are a number of pre-existing conditions that determine the patients' responsiveness to immunotherapy. An immunotherapeutic strategy in which different aspects of immune failure are attacked by complementary approaches, will improve the clinical response rate.

Lobular intraepithelial neoplasia arising within breast fibroadenoma

PubMed Central

2013-01-01

Background Fibroadenomas are the second most common breast pathology occurring in young women under the age of 35 years old. Fibroadenomas can be classified as simple or complex according to histological features. Complex fibroadenomas differ from simple fibroadenomas because of the presence of cysts (3 mm), sclerosing adenosis, epithelial calcifications, or papillary apocrine changes. Most fibroadenomas are clinically identifiable. In 25% of cases, fibroadenomas are non-palpable and are diagnosed with mammography and ultrasound. Differential diagnosis with well differentiated breast cancer is often necessary, particularly with medullary or mucinous tumors. Calcification findings within fibroadenomas by mammogram have to be investigated. The age of a lump is usually reflected by calcifications. Microcalcification can hide foci of carcinoma in situ when they are small, branching type, and heterogeneous. However, many morphological possibilities may not be reliable for deciding whether a certain calcification is the product of a malignant or a benign process. From a radiological point of view, fibroadenomas containing foci of carcinoma in situ can be indistinguishable from benign lesions, even if the incidence of carcinoma within fibroadenomas is estimated as 0.1–0.3%, and it could be a long-term risk factor for invasive breast cancer. Case presentation A 44-year-old woman presented with a 1.5-cm palpable, smooth, mobile lump in the lower-inner quadrant of her right breast. Standard mediolateral oblique and craniocaudal mammograms showed a cluster of eccentric popcorn-like calcifications within the fibroadenoma. After lumpectomy, a definitive histological examination confirmed the intra-operative diagnosis of a benign mass. However, lobular intraepithelial neoplasia foci were found, surrounded by atypical lobular hyperplasia. Conclusions The possibility of an old benign breast lump might be supported by fine needle aspiration biopsy or core biopsy before initiating

World Health Organization Guidelines: Use of cryotherapy for cervical intraepithelial neoplasia.

PubMed

Santesso, Nancy; Schünemann, Holger; Blumenthal, Paul; De Vuyst, Hugo; Gage, Julia; Garcia, Francisco; Jeronimo, Jose; Lu, Ricky; Luciani, Silvana; Quek, Swee C; Awad, Tahany; Broutet, Nathalie

2012-08-01

In 2008, cervical cancer was responsible for 275000 deaths, of which approximately 88% occurred in low- and middle-income countries. In 2009, the World Health Organization (WHO) committed to updating recommendations for use of cryotherapy for cervical intraepithelial neoplasia (CIN). We followed the WHO Handbook for Guidelines Development to develop present guidelines. An expert panel was established, which included clinicians, researchers, program directors, and methodologists. An independent group conducted systematic reviews and produced evidence summaries following the GRADE approach. GRADE evidence profiles were created for 16 key questions about the effects of cryotherapy in the presence of histologically confirmed CIN compared with no treatment and with loop electrosurgical excision procedure, as well as the use of different cryotherapy techniques. We identified a small number of randomized controlled trials or independently controlled observational studies. Surrogate outcomes were reported when evidence about outcomes critical to decision making were not available. The panel made 14 recommendations and documented factors that determined the strength and direction of the recommendations in decision tables. The present document summarizes new evidence-based WHO recommendations about the use of cryotherapy in women with histologically confirmed CIN for low-, middle-, and high-income countries. Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia

NASA Astrophysics Data System (ADS)

Liou, Geou-Yarh; Döppler, Heike; Braun, Ursula B.; Panayiotou, Richard; Scotti Buzhardt, Michele; Radisky, Derek C.; Crawford, Howard C.; Fields, Alan P.; Murray, Nicole R.; Wang, Q. Jane; Leitges, Michael; Storz, Peter

2015-02-01

The transdifferentiation of pancreatic acinar cells to a ductal phenotype (acinar-to-ductal metaplasia, ADM) occurs after injury or inflammation of the pancreas and is a reversible process. However, in the presence of activating Kras mutations or persistent epidermal growth factor receptor (EGF-R) signalling, cells that underwent ADM can progress to pancreatic intraepithelial neoplasia (PanIN) and eventually pancreatic cancer. In transgenic animal models, ADM and PanINs are initiated by high-affinity ligands for EGF-R or activating Kras mutations, but the underlying signalling mechanisms are not well understood. Here, using a conditional knockout approach, we show that protein kinase D1 (PKD1) is sufficient to drive the reprogramming process to a ductal phenotype and progression to PanINs. Moreover, using 3D explant culture of primary pancreatic acinar cells, we show that PKD1 acts downstream of TGFα and Kras, to mediate formation of ductal structures through activation of the Notch pathway.

Possible etiologic heterogeneity of vulvar intraepithelial neoplasia. A correlation of pathologic characteristics with human papillomavirus detection by in situ hybridization and polymerase chain reaction.

PubMed

Park, J S; Jones, R W; McLean, M R; Currie, J L; Woodruff, J D; Shah, K V; Kurman, R J

1991-03-15

A correlated histopathologic and molecular virologic study of 30 cases of vulvar intraepithelial neoplasia Grade 3 (VIN 3) and six associated invasive vulvar carcinomas was performed. Paraffin sections were examined for human papillomavirus (HPV) types 6, 11, 16, and 18 by in situ hybridization for viral transcripts and by polymerase chain reaction (PCR) for amplification of HPV and of the beta-globin gene. Vulvar intraepithelial neoplasia Grade 3 was histologically subclassified into warty (bowenoid) (20 cases) and basaloid (undifferentiated) (ten cases) types. Warty VIN characteristically was composed of squamous cells displaying abnormal proliferation and maturation and an undulating or spiked surface creating a "condylomatous" appearance whereas basaloid VIN had a smooth surface and was composed of undifferentiated basaloid cells resembling carcinoma in situ of the cervix. Human papillomavirus-16 was the only type detected in 16 of 30 VIN 3 and in five of six invasive carcinomas. The HPV-positive women were younger than HPV-negative women (mean age at diagnosis, 49 versus 60 years), their lesions more frequently demonstrated koilocytotic atypia (94% versus 43%), and they were more likely to have warty compared with basaloid VIN lesions (65% versus 30%). These findings suggest that there are at least two different types of VIN which have differing clinical, pathologic, and viral profiles.

Detection of microinvasion in vulvar and cervical intraepithelial neoplasia using double immunostaining for cytokeratin and basement membrane components.

PubMed

Rush, Demaretta; Hyjek, Elizabeth; Baergen, Rebecca N; Ellenson, Lora H; Pirog, Edyta C

2005-06-01

Identification of early invasion in vulvar intraepithelial neoplasia 3 (VIN 3) and cervical intraepithelial neoplasia 3 (CIN 3) may be difficult with the use of routine hematoxylin-eosin staining. Presence of obscuring inflammation and tangential tissue sectioning are the most common diagnostic pitfalls. To examine the utility of double immunostaining for cytokeratin-collagen IV or cytokeratin-laminin in the detection of early invasion in VIN 3 and CIN 3. The study group consisted of 10 cases of "VIN 3, suspicious for invasion" and 10 cases of "CIN 3, suspicious for invasion." The negative control group consisted of VIN 3 (n = 15) and CIN 3 (n = 10). The positive control group consisted of cases of invasive vulvar carcinoma (n = 11) and invasive cervical carcinoma (n = 25). All cases were double immunostained for cytokeratin and collagen IV and, in a separate reaction, for cytokeratin and laminin. The continuity of the basement membrane and the presence of stromal invasion were assessed in the stained sections. The staining for collagen IV and laminin yielded identical results. A well-defined, continuous basement membrane was visualized in all cases of VIN 3 and CIN 3. A discontinuous or absent basement membrane was observed around the malignant cells on the invasive tumor front in all cases of vulvar and cervical carcinoma. In 2 of 10 cases of VIN 3, suspicious for invasion and in 4 of 10 cases of CIN 3, suspicious for invasion definitive foci of microinvasion were identified with the use of double immunostaining. A well-defined, continuous basement membrane was present in the remaining cases "suspicious for invasion." Double immunostaining for cytokeratin- collagen IV or cytokeratin-laminin is useful for evaluation of early invasion in equivocal cases of VIN 3 and CIN 3.

Anal Cytology and Human Papillomavirus Genotyping in Women With a History of Lower Genital Tract Neoplasia Compared With Low-Risk Women.

PubMed

Robison, Katina; Cronin, Beth; Bregar, Amy; Luis, Christine; DiSilvestro, Paul; Schechter, Steven; Pisharodi, Latha; Raker, Christina; Clark, Melissa

2015-12-01

To compare the prevalence of abnormal anal cytology and high-risk human papillomavirus (HPV) among women with a history of HPV-related genital neoplasia with women without a history of HPV-related genital neoplasia. A cross-sectional cohort study was performed from December 2012 to February 2014. Women were recruited from outpatient clinics at an academic medical center. Women with a history of high-grade cervical, vulvar, or vaginal cytology, dysplasia, or cancer were considered the high-risk group. Women with no history of high-grade anogenital dysplasia or cancer were considered the low-risk group. Human immunodeficiency virus-positive women were excluded. Anal cytology and HPV genotyping were performed. Women with abnormal anal cytology were referred for high-resolution anoscopy. There were 190 women in the high-risk group and 83 in the low-risk group. The high-risk group was slightly older: 57 years compared with 47 years (P=.045); 21.7% of low-risk women had abnormal anal cytology compared with 41.2% of high-risk women (P=.006). High-risk HPV was detected in the anal canal of 1.2% of the low-risk group compared with 20.8% of the high-risk group (P<.001). Among women who underwent anoscopy, no anal dysplasia was detected in the low-risk group, whereas 13.4% in the high-risk group had anal dysplasia with 4.2% having anal intraepithelial neoplasia 2 or greater (P<.001). Human immunodeficiency virus-negative women with a history of lower genital tract neoplasia are more likely to have positive anal cytology, anal high-risk HPV, and anal intraepithelial neoplasia. Anal cancer screening should be considered for these high-risk women. II.

Disparities in the Clinical Evolution of Anal Neoplasia in an HIV-Infected Cohort.

PubMed

Cachay, Edward R; Agmas, Wollelaw; Christopher Mathews, Wm

2018-02-01

A recent meta-analysis suggested that anal intraepithelial neoplasia and invasive anal cancer are more prevalent among black men having sex with men (MSM). We conducted a retrospective cohort of HIV-infected adult patients under care between 2001 and 2012. Disparities in clinical evolution of anal intraepithelial neoplasia to high-grade squamous intraepithelial lesion (HSIL) and invasive anal cancer were evaluated in a three-state Markov model adjusted for cytology misclassification. We studied sociodemographic covariate effects for each state transition using multivariable models controlling for antiretroviral therapy and infrared coagulation treatment of HSIL. Among 2804 patients with a median age of 40 years, 78% were MSM and 38% non-white. There were no disparities in HSIL prevalence (14%) by age, sex, race, or risk group. After 4.0 years of follow-up, 23 patients developed invasive anal cancer. Females and black patients had lower transition rates from 40 had lower rates of both intraepithelial neoplasia nor with post-baseline progression of anal intraepithelial neoplasia.

Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia without colposcopic tissue information; a step toward automation for low resource settings

PubMed Central

Zewdie, Getie A.; Cox, Dennis D.; Neely Atkinson, E.; Cantor, Scott B.; MacAulay, Calum; Davies, Kalatu; Adewole, Isaac; Buys, Timon P. H.; Follen, Michele

2012-01-01

Abstract. Optical spectroscopy has been proposed as an accurate and low-cost alternative for detection of cervical intraepithelial neoplasia. We previously published an algorithm using optical spectroscopy as an adjunct to colposcopy and found good accuracy (sensitivity=1.00 [95% confidence interval (CI)=0.92 to 1.00], specificity=0.71 [95% CI=0.62 to 0.79]). Those results used measurements taken by expert colposcopists as well as the colposcopy diagnosis. In this study, we trained and tested an algorithm for the detection of cervical intraepithelial neoplasia (i.e., identifying those patients who had histology reading CIN 2 or worse) that did not include the colposcopic diagnosis. Furthermore, we explored the interaction between spectroscopy and colposcopy, examining the importance of probe placement expertise. The colposcopic diagnosis-independent spectroscopy algorithm had a sensitivity of 0.98 (95% CI=0.89 to 1.00) and a specificity of 0.62 (95% CI=0.52 to 0.71). The difference in the partial area under the ROC curves between spectroscopy with and without the colposcopic diagnosis was statistically significant at the patient level (p=0.05) but not the site level (p=0.13). The results suggest that the device has high accuracy over a wide range of provider accuracy and hence could plausibly be implemented by providers with limited training. PMID:22559693

Cervical Intraepithelial Neoplasia Is Associated With Genital Tract Mucosal Inflammation

PubMed Central

Mhatre, Mohak; McAndrew, Thomas; Carpenter, Colleen; Burk, Robert D.; Einstein, Mark H.; Herold, Betsy C.

2013-01-01

Background Clinical studies demonstrate increased prevalence of human papillomavirus (HPV)-associated disease in HIV-infected individuals and an increased risk of HIV acquisition in HPV-infected individuals. The mechanisms underlying this synergy are not defined. We hypothesize that women with cervical intraepithelial neoplasia (CIN) will exhibit changes in soluble mucosal immunity that may promote HPV persistence and facilitate HIV infection. Methods The concentrations of immune mediators and endogenous anti-Escherichia coli activity in genital tract secretions collected by cervicovaginal lavage were compared in HIV-negative women with high-risk HPV-positive (HRHPV+) CIN-3 (n = 37), HRHPV+ CIN-1 (n = 12), or PAP-negative control subjects (n = 57). Results Compared with control subjects, women with CIN-3 or CIN-1 displayed significantly higher levels of proinflammatory cytokines including interleukin (IL)-1α, IL-1β, and IL-8 (P < 0.002) and significantly lower levels of anti-inflammatory mediators and antimicrobial peptides, including IL-1 receptor antagonist, secretory leukocyte protease inhibitor (P < 0.01), and human β defensins 2 and 3 (P < 0.02). There was no significant difference in endogenous anti-E. coli activity after controlling for age and sample storage time. Conclusion HRHPV+ CIN is characterized by changes in soluble mucosal immunity that could contribute to HPV persistence. The observed mucosal inflammation suggests a mechanism that may also contribute to the epidemiologic link between persistent HPV and HIV. PMID:22801340

Grading of cervical intraepithelial neoplasia using spatial frequency for optical histology

NASA Astrophysics Data System (ADS)

Pu, Yang; Jagtap, Jaidip; Pradhan, Asima; Alfano, Robert R.

2014-03-01

It is important to detect cervical dysplasia, Cervical Intraepithelial Neoplasia (CIN). CIN is the potentially premalignant and abnormal squamous cells on surface of cervix. In this study, the spatial frequency spectra of pre-cancer cervical tissues are used to detect differences among different grades of human cervical tissues. Seven sets of thick tissue sections of human cervix of normal, CIN 1, CIN 2, and CIN 3 tissues are studied. The confocal microscope images of the stromal region of normal and CIN human tissues were analyzed using Fast Fourier Transform (FFT) to generate the spatial spectra. It is observed that higher frequency components exist in CIN tissues than those in normal tissue, as well as those in higher grade CIN tissue than those in lower grade CIN tissue. The width of the spatial frequency of different types of tissues is used to create a criterion for CIN grading by training a support vector machine (SVM) classifier. The results show that the randomness of tissue structures from normal to different stages of precancer in cervical tissue can be recognized by fingerprints of the spatial frequency. The efficacy of spatial frequency analysis for CIN grading is evaluated as excellent since high AUC (area under the ROC curve), sensitivity and specificity are obtained by the statistics study. This works lays the foundation of using spatial frequency spectra for a histology evaluation.

[Behavior of cervical intraepithelial neoplasia in pregnant adolescents and its persistence after an obstetric event].

PubMed

Machain-Loera, Alfredo; Jiménez-Rodríguez, Antonio; Huerta-Casillas, Félix Rafael; Barajas-Serrano, Tanya Lizbeth; Barrera-de León, Juan Carlos

2014-12-01

To observe the behavior of cervical intraepithelial neoplasia in pregnant adolescents and the persistence before the delivery. A cross-sectional study including 47 pregnant adolescents with NIC-positive results diagnosed by colposcopy during pregnancy with subsequent evaluation before the delivery. Nonrandom sampling of consecutive cases. Descriptive statistics with central and dispersal measures. In total, 156 pregnant adolescents were studied, of which 30% (n = 47) had positive results to NIC with subsequent evaluation. Ages 18 ± 1.5 years, primiparous 77%, sexual activity initiation 15.6 ± 1.6 years old, sexual partners 1 (1-6), smoking and alcoholism 21%. At the beginning of pregnancy, 98% had NIC I results and 2% had NIC II by colposcopy. After delivery, 13% had normal results and 87% remained in NIC I. The findings suggest that in pregnant adolescents there exists a natural dysplasia history as in pregnant women. Most of the lesions are NIC I and don't modify the evolution, with some regressing after the delivery.

Population-Based Incidence Rates of Cervical Intraepithelial Neoplasia in the Human Papillomavirus Vaccine Era.

PubMed

Benard, Vicki B; Castle, Philip E; Jenison, Steven A; Hunt, William C; Kim, Jane J; Cuzick, Jack; Lee, Ji-Hyun; Du, Ruofei; Robertson, Michael; Norville, Scott; Wheeler, Cosette M

2017-06-01

A substantial effect of human papillomavirus (HPV) vaccines on reducing HPV-related cervical disease is essential before modifying clinical practice guidelines in partially vaccinated populations. To determine the population-based cervical intraepithelial neoplasia (CIN) trends when adjusting for changes in cervical screening practices that overlapped with HPV vaccination implementation. The New Mexico HPV Pap Registry, which captures population-based estimates of both cervical screening prevalence and CIN, was used to compute CIN trends from January 1, 2007, to December 31, 2014. Under New Mexico Administrative Code, the New Mexico HPV Pap Registry, a statewide public health surveillance program, receives mandatory reporting of all cervical screening (cytologic and HPV testing) and any cervical, vulvar, and vaginal histopathological findings for all women residing in New Mexico irrespective of outcome. Prespecified outcome measures included low-grade CIN (grade 1 [CIN1]) and high-grade CIN (grade 2 [CIN2] and grade 3 [CIN3]). From 2007 to 2014, a total of 13 520 CIN1, 4296 CIN2, and 2823 CIN3 lesions were diagnosed among female individuals 15 to 29 years old. After adjustment for changes in cervical screening across the period, reductions in the CIN incidence per 100 000 women screened were significant for all grades of CIN among female individuals 15 to 19 years old, dropping from 3468.3 to 1590.6 for CIN1 (annual percentage change [APC], -9.0; 95% CI, -12.0 to -5.8; P < .001), from 896.4 to 414.9 for CIN2 (APC, -10.5; 95% CI, -18.8 to -1.2; P = .03), and from 240.2 to 0 for CIN3 (APC, -41.3; 95% CI, -65.7 to 0.3; P = .05). Reductions in the CIN2 incidence were also significant for women 20 to 24 years old, dropping from 1027.7 to 627.1 (APC, -6.3; 95% CI, -10.9 to -1.4; P = .02). Population-level decreases in CIN among cohorts partially vaccinated for HPV may be considered when clinical practice guidelines for cervical cancer screening are

[Shall all lobular intraepithelial neoplasia diagnosed on image-guided biopsy require a surgical management?].

PubMed

Fischer-Hunsinger, Maeva; Guinebretière, Jean-Marc; Lasry, Serge; Langer, Adriana; Berment, Hélène; Nekka, Ibtissem; Nodiot, Philippe; Cherel, Pascal

2016-05-01

Lobular intraepithelial neoplasia (LIN) diagnosed on image-guided biopsy may be associated with an undiagnosed cancer. This is called under-diagnosis. The consequence is that management of these lesions is often surgical. But many surgeries finally are unnecessary. The aim of our study was to define criteria to avoid unnecessary surgery. This is a single-center, retrospective after a database collected prospectively study. Fourteen thousand biopsies were analyzed, including 456 diagnosed NLI. Under-diagnosis rates were analyzed according to many criteria. The average duration of following was 45 months. For atypical lobular hyperplasia (ALH), we obtained 7.6% under-diagnosis and combining several criteria, we got a low risk of cancer (2%). For LCIS, this rate was 23% and any low-risk group could be identified. ALH with calcifications≤20 mm, without any atypical lesion associated, histologically focal and whose removal is representative may be safely observed. For other LIN, surgery remains indicated. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Protective effect of zinc on N-methyl-N-nitrosourea and testosterone-induced prostatic intraepithelial neoplasia in the dorsolateral prostate of Sprague Dawley rats.

PubMed

Banudevi, Sivanantham; Elumalai, Perumal; Sharmila, Govindaraj; Arunkumar, Ramachandran; Senthilkumar, Kalimuthu; Arunakaran, Jagadeesan

2011-09-01

Previous studies have suggested that zinc exerts anticarcinogenic and antiproliferative effects against prostate cancer both in vitro and in rat ventral prostate. Zinc accumulation diminishes early in the course of prostate malignancy and it inhibits the growth of several carcinoma cells through induction of cell cycle arrest and apoptosis. In this study, we have investigated the influence of zinc on N-methyl-N-nitrosourea (MNU) and testosterone (T)-induced prostatic intraepithelial neoplasia in the dorsolateral prostate of Sprague Dawley (SD) rats. The results indicate that zinc plays an important role in prostate carcinogenesis. Increased tumor incidence was accompanied by a decrease in prostatic acid phosphatase activity, citrate, zinc, glutathione-S-transferase, reduced glutathione, p53, B-cell lymphoma protein (Bcl-2)-associated X protein and caspase-3 levels in MNU + T-treated rats. On the contrary, significantly increased phase I drug metabolizing enzyme activities, lipid peroxide, hydrogen peroxide, proliferating cell nuclear antigen, Bcl-2 and Bcl-X(L) protein levels were observed in the dorsolateral prostate of MNU + T-treated rats. Simultaneous zinc supplementation significantly reversed these effects in MNU + T-treated rats. Signs of dysplasia, a characteristic of prostatic intraepithelial neoplasia, were evident in the dorsolateral prostatic tissue sections by MNU + T administration. However, zinc supplementation has reversed these effects in the dorsolateral prostatic histoarchitecture. These results suggest that zinc may act as an essential trace element against MNU and testosterone-induced prostatic preneoplastic progression in SD rats.

Photodynamic therapy of vulvar intraepithelial neoplasia using 5-aminolevulinic acid.

PubMed

Hillemanns, P; Untch, M; Dannecker, C; Baumgartner, R; Stepp, H; Diebold, J; Weingandt, H; Pröve, F; Korell, M

2000-03-01

Photodynamic (PDT) therapy is a relatively new technique with unique properties that make it attractive for the local treatment of superficial epithelial disorders. The objective of this study was to investigate the clinical response of PDT with the photosensitizing agent 5-aminolevulinic acid (5-ALA) in patients with vulvar intraepithelial neoplasia (VIN) grades 1 to 3. Twenty-five patients with 111 lesions of VIN 1-3 were topically sensitized with 10 ml of a 20% solution of 5-ALA and treated with 57 cycles of laser light at 635 nm (100 J/cm(2)). Seventy (64%) of the 111 VIN lesions regressed after various PDT cycles. A complete response was achieved in 13 patients (52%) with 27 lesions. All patients with VIN 1 and mono- and bifocal VIN 2-3 showed complete clearance. However, a complete response could be achieved in only 4 (27%) of 15 women with multifocal VIN 2-3, whereas a partial response was noted in 9 of these patients with a total of 70 lesions, out of which 44 (63%) lesions disappeared. No response was seen in 2 patients with multifocal VIN 3. Histological assessment of the fluorescence-directed biopsies revealed that increased pigmentation and hyperkeratosis of the lesions were associated with low response rates. PDT using 5-ALA represents an alternative treatment modality for VIN which is easy to perform and has the advantage of minimal tissue destruction, low side effects and excellent cosmetic results. However, multifocal VIN disease with pigmented and hyperkeratinic lesions remains difficult to treat. Copyright 2000 Wiley-Liss, Inc.

Do clinical data and human papilloma virus genotype influence spontaneous regression in grade I cervical intraepithelial neoplasia?

PubMed

Cortés-Alaguero, Caterina; González-Mirasol, Esteban; Morales-Roselló, José; Poblet-Martinez, Enrique

2017-03-15

To determine whether medical history, clinical examination and human papilloma virus (HPV) genotype influence spontaneous regression in cervical intraepithelial neoplasia grade I (CIN-I). We retrospectively evaluated 232 women who were histologically diagnosed as have CIN-I by means of Kaplan-Meier curves, the pattern of spontaneous regression according to the medical history, clinical examination, and HPV genotype. Spontaneous regression occurred in most patients and was influenced by the presence of multiple HPV genotypes but not by the HPV genotype itself. In addition, regression frequency was diminished when more than 50% of the cervix surface was affected or when an abnormal cytology was present at the beginning of follow-up. The frequency of regression in CIN-I is high, making long-term follow-up and conservative management advisable. Data from clinical examination and HPV genotyping might help to anticipate which lesions will regress.

Restricted surgical management of vulvar intraepithelial neoplasia 3: Focus on exclusion of invasion and on relief of symptoms.

PubMed

van Beurden, M.; van Der Vange, N.; ten Kate, F. J. W.; de Craen, A. J. M.; Schilthuis, M. S.; Lammes, F. B.

1998-01-01

van Beurden M, van der Vange N, ten Kate FJW, de Craen AJM, Schilthuis MS, Lammes FB. Restricted surgical management of vulvar intraepithelial neoplasia 3: Focus on exclusion of invasion and on relief of symptoms. Int J Gynecol Cancer 1998; 8: 73-77. A study was undertaken to determine the effectiveness of extensive and restricted surgery for vulvar intraepithelial neoplasia (VIN) 3. All consecutive patients with VIN 3 admitted to a tertiary referral hospital were included. The main outcome measures were relief and recurrence of symptoms and progression to invasive disease in patients with VIN 3 after extensive or restricted surgery. Of every vulvoscopic visible lesion a biopsy was taken to establish extent and grade of VIN and to rule out invasive carcinoma. Patients with unifocal VIN 3 underwent extensive surgery. Patients with multifocal VIN 3 underwent extensive or restricted surgery or an expectant management was adopted, depending on the existence of symptoms and the presence of invasive vulvar carcinoma. Forty-seven patients were evaluated. Eighty-three percent of patients had a long history of symptoms. Eight patients (17%) had unifocal VIN 3. In 9% of the patients a superficially invasive vulvar carcinoma was found, ie with a depth of invasion of 1 mm or less. Only 20% of the extensively operated patients had free surgical margins. There was recurrence of symptoms in all of the extensively operated patients, in contrast to a 26% persistence or recurrence rate of symptoms in the restrictedly operated patients. In patients with multifocal VIN 3 who underwent restricted surgery, young age of the patient (P = 0.02) and large extension of VIN 3 (P = 0.02) were significant factors in predicting persistence or recurrence of symptoms. Only once was a superficially invasive vulvar carcinoma diagnosed during follow-up, and this was in an extensively operated patient. Vulvoscopically directed biopsies in VIN 3 are a safe method to exclude invasive disease. Restricted

Anal intraepithelial neoplasia: A review of diagnosis and management

PubMed Central

Roberts, Joseph R; Siekas, Lacey L; Kaz, Andrew M

2017-01-01

Anal intraepithelial neoplasia (AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the United States, and among certain high risk populations the incidence of anal cancer may exceed that of colon cancer. Risk factors for AIN and anal cancer consist of clinical factors and behaviors that are associated with the acquisition and persistence of human papilloma virus (HPV) infection. The strongest HPV-associated risk factors are HIV infection, receptive anal intercourse, and high risk sexual behavior. A history of HPV-mediated genital cancer, which suggests infection with an oncogenic HPV strain, is another risk factor for AIN/anal cancer. Because progression of AIN to anal cancer is known to occur in some individuals over several years, screening for AIN and early anal cancer, as well as treatment of advanced AIN lesions, is reasonable in certain high-risk populations. Although randomized controlled trials evaluating screening and treatment outcomes are lacking, experts support routine screening for AIN in high risk populations. Screening is performed using anal cytological exams, similar to those performed in cervical cancer screening programs, along with direct tissue evaluation and biopsy via high resolution anoscopy. AIN can be treated using topical therapies such as imiquimod, 5-flurouracil, and trichloroacetic acid, as well as ablative therapies such as electrocautery and laser therapy. Reductions in AIN and anal cancer rates have been shown in studies where high-risk populations were vaccinated against the oncogenic strains of HPV. Currently, the CDC recommends both high-risk and average-risk populations be vaccinated against HPV infection using the quadrivalent or nonavalent vaccines. It is important for clinicians to be familiar with AIN and the role of HPV vaccination, particularly in high risk populations. PMID:28255426

Anal intraepithelial neoplasia: A review of diagnosis and management.

PubMed

Roberts, Joseph R; Siekas, Lacey L; Kaz, Andrew M

2017-02-15

Anal intraepithelial neoplasia (AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the United States, and among certain high risk populations the incidence of anal cancer may exceed that of colon cancer. Risk factors for AIN and anal cancer consist of clinical factors and behaviors that are associated with the acquisition and persistence of human papilloma virus (HPV) infection. The strongest HPV-associated risk factors are HIV infection, receptive anal intercourse, and high risk sexual behavior. A history of HPV-mediated genital cancer, which suggests infection with an oncogenic HPV strain, is another risk factor for AIN/anal cancer. Because progression of AIN to anal cancer is known to occur in some individuals over several years, screening for AIN and early anal cancer, as well as treatment of advanced AIN lesions, is reasonable in certain high-risk populations. Although randomized controlled trials evaluating screening and treatment outcomes are lacking, experts support routine screening for AIN in high risk populations. Screening is performed using anal cytological exams, similar to those performed in cervical cancer screening programs, along with direct tissue evaluation and biopsy via high resolution anoscopy. AIN can be treated using topical therapies such as imiquimod, 5-flurouracil, and trichloroacetic acid, as well as ablative therapies such as electrocautery and laser therapy. Reductions in AIN and anal cancer rates have been shown in studies where high-risk populations were vaccinated against the oncogenic strains of HPV. Currently, the CDC recommends both high-risk and average-risk populations be vaccinated against HPV infection using the quadrivalent or nonavalent vaccines. It is important for clinicians to be familiar with AIN and the role of HPV vaccination, particularly in high risk populations.

Clinical approach to vaginal/vestibular masses in the bitch.

PubMed

Manothaiudom, K; Johnston, S D

1991-05-01

The most common causes of vaginal/vestibular masses in the bitch are vaginal prolapse, vaginal neoplasia, and urethral neoplasia protruding into the vaginal vault. Other possible causes are clitoral enlargement, vaginal polyps, uterine prolapse, and vaginal abscessation or hematoma. Vaginal prolapse usually can be distinguished from neoplasia by the age of the patient, the time of occurrence during the estrous cycle, and the site of origin of the mass. Prolapse usually occurs in bitches under 4 years of age during proestrus, estrus, or at the end of diestrus and usually arises from the floor of the vagina, except for urethral tumors that protrude from the external urethral orifice. Appropriate diagnostic workup of bitches with vaginal vestibular masses includes complete history and physical examination, vaginal cytologic and vaginoscopic examination, retrograde vaginography or urethrocystography, serum progesterone and estradiol concentrations, and, in the case of suspect neoplasms, surgical or excision biopsy of the mass.

The Human Papillomavirus Vaccine: Current Perspective and Future Role in Prevention and Treatment of Anal Intraepithelial Neoplasia and Anal Cancer

PubMed Central

Mehta, Mudresh R.; Lewis, James S.; Lockhart, A. Craig

2016-01-01

The incidences of human papillomavirus (HPV)-related anal cancer and its precursor lesion, anal intraepithelial neoplasia, are rising in the U.S. and globally. Five-year survival rates with current modalities of treatment for anal cancer are generally favorable for localized and regional disease. For metastatic disease, the relative survival rate is poor. Major contributing factors for the increase in anal cancer incidence include increasing receptive anal intercourse (hetero- and homosexual), increasing HPV infections, and longer life expectancy of treated people who are seropositive for human immunodeficiency virus. Because treatment outcomes with systemic therapy in patients with advanced disease are so poor, prevention may be the best approach for reducing disease burden. The association of a major causative agent with anal cancer provides an excellent opportunity for prevention and treatment. The advent of the HPV vaccine for anal cancer prevention and treatment is a significant milestone and has the potential to greatly impact these cancers. The data regarding potential use of the HPV vaccine in anal cancer prevention and treatment are reviewed. Implications for Practice: The incidences of human papillomavirus (HPV)-related anal cancer and its precursor lesion, anal intraepithelial neoplasia, are on the rise in the U.S. and globally. Based on recent studies, the HPV vaccine is approved for prevention of the infection and development of HPV-related anal cancer. In addition, several small studies have shown that the vaccine may be useful as adjuvant therapy for anal cancer. There is a need for public health strategies aimed at education of both patients and practitioners to improve the use of the vaccine for prevention of HPV-related anal cancer. The development of a therapeutic vaccine is a work in progress. PMID:26961923

IL2RG, identified as overexpressed by RNA-seq profiling of pancreatic intraepithelial neoplasia, mediates pancreatic cancer growth

PubMed Central

Ayars, Michael; O’Sullivan, Eileen; Macgregor-Das, Anne; Shindo, Koji; Kim, Haeryoung; Borges, Michael; Yu, Jun; Hruban, Ralph H.; Goggins, Michael

2017-01-01

Pancreatic ductal adenocarcinoma evolves from precursor lesions, the most common of which is pancreatic intraepithelial neoplasia (PanIN). We performed RNA-sequencing analysis of laser capture microdissected PanINs and normal pancreatic duct cells to identify differentially expressed genes between PanINs and normal pancreatic duct, and between low-grade and high-grade PanINs. One of the most highly overexpressed transcripts identified in PanIN is interleukin-2 receptor subunit gamma (IL2RG) encoding the common gamma chain, IL2Rγ. CRISPR-mediated knockout of IL2RG in orthotopically implanted pancreatic cancer cells resulted in attenuated tumor growth in mice and reduced JAK3 expression in orthotopic tumors. These results indicate that IL2Rγ/JAK3 signaling contributes to pancreatic cancer cell growth in vivo. PMID:29137350

In vivo and in vitro hyperspectral imaging of cervical neoplasia

NASA Astrophysics Data System (ADS)

Wang, Chaojian; Zheng, Wenli; Bu, Yanggao; Chang, Shufang; Tong, Qingping; Zhang, Shiwu; Xu, Ronald X.

2014-02-01

Cervical cancer is a prevalent disease in many developing countries. Colposcopy is the most common approach for screening cervical intraepithelial neoplasia (CIN). However, its clinical efficacy heavily relies on the examiner's experience. Spectroscopy is a potentially effective method for noninvasive diagnosis of cervical neoplasia. In this paper, we introduce a hyperspectral imaging technique for noninvasive detection and quantitative analysis of cervical neoplasia. A hyperspectral camera is used to collect the reflectance images of the entire cervix under xenon lamp illumination, followed by standard colposcopy examination and cervical tissue biopsy at both normal and abnormal sites in different quadrants. The collected reflectance data are calibrated and the hyperspectral signals are extracted. Further spectral analysis and image processing works are carried out to classify tissue into different types based on the spectral characteristics at different stages of cervical intraepithelial neoplasia. The hyperspectral camera is also coupled with a lab microscope to acquire the hyperspectral transmittance images of the pathological slides. The in vivo and the in vitro imaging results are compared with clinical findings to assess the accuracy and efficacy of the method.

Large loop excision of the transformation zone for treating cervical intraepithelial neoplasia: a 12-year experience.

PubMed

Paraskevaidis, E; Koliopoulos, G; Malamou-Mitsi, V; Zikopoulos, K; Paschopoulos, M; Pappa, L; Agnantis, N J; Loli, D E

2001-01-01

Although the existing evidence suggests that there is no obviously superior conservative method for treating cervical intraepithelial neoplasia (CIN), one of the most widely used is the large loop excision of the transformation zone (LLETZ). A total of 897 women who were treated with LLETZ at our colposcopy clinic from 1989 to 2000 were retrospectively studied. Forty women did not have significant cervical pathology (4.5% over-treatment rate). Clear margins of excision were obtained in 748 (88.5%) of the 845 cases of CIN or microinvasive cancers. Treatment failure rates were 4.7% for clear margins and 26.8% for involved or uncertain. LLETZ is a fast and reliable method of treating CIN and microinvasive carcinoma. Generalized cauterization of the resulting crater should be avoided and satellite HPV lesions ablated. Involved margins have a higher treatmentfailure rate, therefore a larger excision is recommended as cervical craters regenerate. Treatment in pregnant women can be delayed until postpartum provided they have adequate surveillance during pregnancy.

Human papillomavirus in invasive cervical cancer and cervical intraepithelial neoplasia 2 and 3 in Venezuela: a cross-sectional study.

PubMed

Sánchez-Lander, Jorge; Cortiñas, Paula; Loureiro, Carmen Luisa; Pujol, Flor Helene; Medina, Francisco; Capote-Negrín, Luis; Bianchi, Gino; García-Barriola, Victoria; Ruiz-Benni, Angela; Avilán-Rovira, José; Acosta, Humberto

2012-10-01

This study investigated the distribution of human papillomavirus (HPV) types in invasive cervical cancer (ICC), cervical intraepithelial neoplasia 2 (CIN2) and cervical intraepithelial neoplasia 3 (CIN3) in Venezuela. Paraffin-embedded samples from 329 women from 29 medical centers of the 24 states of Venezuela were analyzed to determine the distribution of HPV types for ICC, CIN2, and CIN3, the prevalence of single and multiple infection, and the association of HPV types with severity of lesion, comparing CIN2 versus CIN3+ (CIN3 and ICC). The samples were analyzed with the polymerase chain reaction (PCR) followed by reverse hybridization for the identification of HPV types. HPV was identified in 95/96 ICC specimens (98.9%), in 142/149 CIN3 (95.3%) and in 78/84 CIN2 samples (92.8%). The most common types for ICC and CIN3 were: HPV16, 18, 31, and 33, and for CIN2 were HPV16, 31, 51, 52, and 18. HPV single infection was found in 82.1% of ICC cases, in 79.4% of CIN2 cases, and in 77.4% of CIN3 cases. HPV16 was identified as a single infection more frequently in women with CIN3+ than in those with CIN2 (68.6% versus 46.7%, P=0.002), and HPV16 or HPV18 types were more prevalent in CIN3+ than in CIN2 (73.4% versus 50%, P=0.0006). this is the first study of the distribution of HPV types in ICC, CIN2, and CIN3 conducted throughout the territory of Venezuela. HPV16 and HPV18 were the most frequent HPV types identified in single and multiple infections in both ICC and CIN3 groups, and are associated with severity of lesion. The knowledge of the distribution of HPV types would allow organization of an HPV-DNA-based screening test, and consideration of the implementation of prophylactic vaccination in Venezuela. Copyright © 2012 Elsevier Ltd. All rights reserved.

Discrepant HPV/cytology cotesting results: Are there differences between cytology-negative versus HPV-negative cervical intraepithelial neoplasia?

PubMed

Tracht, Jessica M; Davis, Antoinette D; Fasciano, Danielle N; Eltoum, Isam-Eldin A

2017-10-01

The objective of this study was to compare cervical high-grade squamous intraepithelial lesions subcategorized as cervical intraepithelial neoplasia-3 (CIN-3)-positive after a negative cytology result but positive for high-risk human papillomavirus (HR-HPV) testing to those with a negative HR-HPV test but positive cytology (atypical squamous cells of undetermined significance [ASCUS]-positive/HPV-negative) and to assess reasons for discrepancies. The authors retrospectively analyzed women who underwent screening with cytology and HPV testing from 2010 through 2013. After a review of surgical specimens and cytology, discrepancies were classified as sampling or interpretation error. Clinical and pathologic findings were compared. In total, 15,173 women (age range, 25-95 years; 7.1% were aged < 30 years) underwent both HPV and cytologic testing, and 1184 (8.4%) underwent biopsy. Cytology was positive in 19.4% of specimens, and HPV was positive in 14.5%. Eighty-four CIN-3-positive specimens were detected, including 55 that tested ASCUS-positive/HPV-positive, 11 that tested negative for intraepithelial lesion or malignancy (NILM)/HPV-positive, 10 that tested ASCUS-positive/HPV-negative, 3 that tested NILM/HPV-negative, and 5 tests that were unsatisfactory. There was no significant difference between NILM/HPV-positive and ASCUS-positive/HPV-negative CIN-3 in terms of size, time to occurrence, the presence of a cytopathic effect, screening history, race, or age. Six of 11 NILM/HPV-positive cases were reclassified as ASCUS, indicating an interpreting error of 55% and a sampling error of 45%. No ASCUS-positive/HPV-negative cases were reclassified. Seven cases of CIN-3 with positive cytology were HPV-negative. There are no significant clinical or pathologic differences between NILM/HPV-positive and ASCUS-positive/HPV-negative CIN-3-positive specimens. Cytologic sampling or interpretation remains the main reason for discrepancies. However, HPV-negative CIN-3 with positive

Vulvar Cancer—Patient Version

Cancer.gov

Vulvar cancer usually forms slowly, most often on the vaginal lips or the sides of the vaginal opening. Having vulvar intraepithelial neoplasia or human papillomavirus (HPV) infection can increase the risk of developing vulvar cancer. Start here to find information on vulvar cancer treatment, research, and statistics.

The 2015 International Society for the Study of Vulvovaginal Disease (ISSVD) Terminology of Vulvar Squamous Intraepithelial Lesions.

PubMed

Bornstein, Jacob; Bogliatto, Fabrizio; Haefner, Hope K; Stockdale, Colleen K; Preti, Mario; Bohl, Tanja G; Reutter, Jason

2016-02-01

The impact of terminology for vulvar intraepithelial lesions has been significant over the years, because it has affected diagnosis, treatment, and research. The introduction of the Lower Anogenital Squamous Terminology (LAST) in 2012 raised 2 concerns in relation to vulvar lesions: firstly, the absence of reference to "differentiated vulvar intraepithelial neoplasia" (differentiated VIN) could lead to its being overlooked by health care providers, despite its malignant potential. Secondly, including the term "low-grade squamous intraepithelial lesion" (LSIL) in LAST recreated the potential for overdiagnosis and overtreatment for benign, self-limiting lesions. The International Society for the Study of Vulvovaginal Disease (ISSVD) assigned the terminology committee the task of developing a terminology to take these issues into consideration. The committee reviewed the development of terminology for vulvar SILs with the previous 2 concerns in mind and reviewed several new terminology options. The final version accepted by the ISSVD contains the following: 1) Low-grade SIL of the vulva or vulvar LSIL, encompassing flat condyloma or human papillomavirus effect. 2) High-grade SIL or vulvar HSIL (which was termed "vulvar intraepithelial neoplasia usual type" in the 2004 ISSVD terminology). 3) Vulvar intraepithelial neoplasia, differentiated type. The advantage of the new terminology is that it includes all types of vulvar SILs, it provides a solution to the concerns in relation to the application of LAST to vulvar lesion, and it is in accordance with the World Health Organization classification as well as the LAST, creating unity among clinicians and pathologists.

The 2015 International Society for the Study of Vulvovaginal Disease (ISSVD) Terminology of Vulvar Squamous Intraepithelial Lesions.

PubMed

Bornstein, Jacob; Bogliatto, Fabrizio; Haefner, Hope K; Stockdale, Colleen K; Preti, Mario; Bohl, Tanja G; Reutter, Jason

2016-01-01

The impact of terminology for vulvar intraepithelial lesions has been significant over the years, because it has affected diagnosis, treatment, and research. The introduction of the Lower Anogenital Squamous Terminology (LAST) in 2012 raised 2 concerns in relation to vulvar lesions: firstly, the absence of reference to "differentiated vulvar intraepithelial neoplasia" (differentiated VIN) could lead to its being overlooked by health care providers, despite its malignant potential. Secondly, including the term "low-grade squamous intraepithelial lesion" (LSIL) in LAST recreated the potential for overdiagnosis and overtreatment for benign, self-limiting lesions. The International Society for the Study of Vulvovaginal Disease (ISSVD) assigned the terminology committee the task of developing a terminology to take these issues into consideration. The committee reviewed the development of terminology for vulvar SILs with the previous 2 concerns in mind and reviewed several new terminology options. The final version accepted by the ISSVD contains the following:•Low-grade SIL of the vulva or vulvar LSIL, encompassing flat condyloma or human papillomavirus effect.•High-grade SIL or vulvar HSIL (which was termed "vulvar intraepithelial neoplasia usual type" in the 2004 ISSVD terminology).•Vulvar intraepithelial neoplasia, differentiated type. The advantage of the new terminology is that it includes all types of vulvar SILs, it provides a solution to the concerns in relation to the application of LAST to vulvar lesion, and it is in accordance with the World Health Organization classification as well as the LAST, creating unity among clinicians and pathologists.

Population-Based Incidence Rates of Cervical Intraepithelial Neoplasia in the Human Papillomavirus Vaccine Era

PubMed Central

Benard, Vicki B.; Castle, Philip E.; Jenison, Steven A.; Hunt, William C.; Kim, Jane J.; Cuzick, Jack; Lee, Ji-Hyun; Du, Ruofei; Robertson, Michael; Norville, Scott; Wheeler, Cosette M.

2018-01-01

IMPORTANCE A substantial effect of human papillomavirus (HPV) vaccines on reducing HPV-related cervical disease is essential before modifying clinical practice guidelines in partially vaccinated populations. OBJECTIVE To determine the population-based cervical intraepithelial neoplasia (CIN) trends when adjusting for changes in cervical screening practices that overlapped with HPV vaccination implementation. DESIGN, SETTING, AND PARTICIPANTS The New Mexico HPV Pap Registry, which captures population-based estimates of both cervical screening prevalence and CIN, was used to compute CIN trends from January 1, 2007, to December 31, 2014. Under New Mexico Administrative Code, the New Mexico HPV Pap Registry, a statewide public health surveillance program, receives mandatory reporting of all cervical screening (cytologic and HPV testing) and any cervical, vulvar, and vaginal histopathological findings for all women residing in New Mexico irrespective of outcome. MAIN OUTCOME MEASURES Prespecified outcome measures included low-grade CIN (grade 1 [CIN1]) and high-grade CIN (grade 2 [CIN2] and grade 3 [CIN3]). RESULTS From 2007 to 2014, a total of 13 520 CIN1, 4296 CIN2, and 2823 CIN3 lesions were diagnosed among female individuals 15 to 29 years old. After adjustment for changes in cervical screening across the period, reductions in the CIN incidence per 100 000 women screened were significant for all grades of CIN among female individuals 15 to 19 years old, dropping from 3468.3 to 1590.6 for CIN1 (annual percentage change [APC], −9.0; 95% CI, −12.0 to −5.8; P < .001), from 896.4 to 414.9 for CIN2 (APC, −10.5; 95% CI, −18.8 to −1.2; P = .03), and from 240.2 to 0 for CIN3 (APC, −41.3; 95% CI, −65.7 to 0.3; P = .05). Reductions in the CIN2 incidence were also significant for women 20 to 24 years old, dropping from 1027.7 to 627.1 (APC, −6.3; 95% CI, −10.9 to −1.4; P = .02). CONCLUSIONS AND RELEVANCE Population-level decreases in CIN among cohorts

Local expression of interferon-alpha and interferon receptors in cervical intraepithelial neoplasia.

PubMed

Tirone, Nelson R; Peghini, Bethanea C; Barcelos, Ana Cristina M; Murta, Eddie F C; Michelin, Marcia A

2009-12-01

The present study evaluated mRNA expression of interferon-alpha (IFN-alpha), IFN-alpha receptor subunits (IFNAR-1 and IFNAR-2) and an IFN-stimulated gene encoding the enzyme 2',5'-oligoadenylate synthetase (2'5'OAS) in biopsies on patients with varying grades of cervical intraepithelial neoplasia (CIN I, II and III). Uterine cervix biopsies were collected from women with CIN I, II and III (n = 28) and controls without CIN lesions or human papilloma virus (HPV) infection (n = 17). The presence of high and low-risk HPV DNA was determined using hybrid capture. The mRNA levels of IFNAR-1, IFNAR-2, IFN-alpha and 2'5'OAS were determined by RT-PCR with specific primers. The control group exhibited a greater frequency of IFNAR-1 expression (10/17; 58.3%) than the CIN samples (4/28; 14.2%) (P = 0.0018), while, the expression of IFNAR-2 was also greater in the control samples (11/17; 64.7%) than in the patients with lesions (2/28; 7.1%) (P = 0.0018). Importantly, simultaneous expression of both receptors was observed only in the control group (8/17; 47.0%) (P = 0.0001). Among the CIN samples, there was one case of low expression of mRNA of IFNAR-1 and IFNAR-2. IFN-alpha was present in 14.2% (4/28) of the CIN samples but was not expressed in the control group. mRNA 2'5'OAS were expressed in 28.5% (8/28) of the CIN samples and 11.7% (2/17) of the control samples (not statistically significant). Fifty percent (14/28) of the CIN samples were positive for HPV DNA. Cervical biopsy samples from control women or those without neoplasia or HPV infection displayed higher IFN-alpha receptor expression than those with CIN, while simultaneous expression of both IFN-alpha receptor subunits was found only in the control group. There was no significant difference in mRNA expression of IFN-alpha and 2'5'OAS between the control and CIN groups. Then we concluded that the samples obtained from patients with CIN present low levels of the IFN-alpha receptor mRNA.

Circulating Soluble Neuropilin-1 in Patients with Early Cervical Cancer and Cervical Intraepithelial Neoplasia Can Be Used as a Valuable Diagnostic Biomarker

PubMed Central

Yang, Shouhua; Cheng, Henghui; Huang, Zaiju; Wang, Xiaoling; Wan, Yinglu; Cai, Jing; Wang, Zehua

2015-01-01

Objective. To investigate soluble neuropilin-1 (sNRP-1) in circulating and NRP-1 protein in cervical tissues from patients with cervical cancer or cervical intraepithelial neoplasia (CIN). Methods. sNRP-1 was measured in 64 preoperative patients and 20 controls. NRP-1 protein in cervical tissue was detected in 56 patients and 20 controls. Results. Both sNRP-1 and NRP-1 proteins were correlated with stage. sNRP-1 presented a high diagnostic ability of cervical cancer and CIN, with a sensitivity of 70.97% and a specificity of 73.68%. Conclusions. sNRP-1 in circulating can serve as a possible valuable diagnostic biomarker for cervical cancer and CIN. PMID:25873749

An update on vulvar intraepithelial neoplasia: terminology and a practical approach to diagnosis.

PubMed

Reyes, M Carolina; Cooper, Kumarasen

2014-04-01

There are two distinct types of vulvar intraepithelial neoplasia (VIN), which differ in their clinical presentation, aetiology, pathogenesis and histological/immunophenotypical features. One form driven by high-risk human papilloma virus infection usually occurs in young women and has been termed classic or usual VIN (uVIN). The other, not related to viral infection, occurs in postmenopausal women with chronic skin conditions such as lichen sclerosus and lichen simplex chronicus and is termed differentiated or simplex-type VIN. The latter is the precursor lesion of the most common type of squamous cell carcinoma (SCC) in the vulva, namely keratinizing SCC (representing 60% of cases). In contrast, uVIN usually gives rise to basaloid or warty SCC (40% of cases). The histological features of uVIN are similar to those of high grade lesions encountered in other lower anogenital tract sites (hyperchomatic nuclei with high nuclear to cytoplasmic ratios and increased mitotic activity). However, differentiated VIN has very subtle histopathological changes and often escapes diagnosis. Since uVIN is driven by high-risk human papilloma virus infections, p16 immunohistochemistry is diffusely positive in these lesions and is characterized with a high Ki-67 proliferation index. In contrast, differentiated or simplex-type VIN is consistently negative for p16 and the majority of the cases harbour TP53 mutations, correlating with p53 positivity by immunohistochemistry.

Comparison between two portable devices for widefield PpIX fluorescence during cervical intraepithelial neoplasia treatment

NASA Astrophysics Data System (ADS)

Carbinatto, Fernanda M.; Inada, Natalia Mayumi; Lombardi, Welington; Cossetin, Natália Fernandez; Varoto, Cinthia; Kurachi, Cristina; Bagnato, Vanderlei Salvador

2015-06-01

The use of portable electronic devices, in particular mobile phones such as smartphones is increasing not only for all known applications, but also for diagnosis of diseases and monitoring treatments like topical Photodynamic Therapy. The aim of the study is to evaluate the production of the photosensitizer Protoporphyrin IX (PpIX) after topical application of a cream containing methyl aminolevulinate (MAL) in the cervix with diagnosis of Cervical Intraepithelial Neoplasia (CIN) through the fluorescence images captured after one and three hours and compare the images using two devices (a Sony Xperia® mobile and an Apple Ipod®. Was observed an increasing fluorescence intensity of the cervix three hours after cream application, in both portable electronic devices. However, because was used a specific program for the treatment of images using the Ipod® device, these images presented better resolution than observed by the Sony cell phone without a specific program. One hour after cream application presented a more selective fluorescence than the group of three hours. In conclusion, the use of portable devices to obtain images of PpIX fluorescence shown to be an effective tool and is necessary the improvement of programs for achievement of better results.

Regeneration of cervix after excisional treatment for cervical intraepithelial neoplasia: a study of collagen distribution.

PubMed

Phadnis, S V; Atilade, A; Bowring, J; Kyrgiou, M; Young, M P A; Evans, H; Paraskevaidis, E; Walker, P

2011-12-01

To study the distribution of collagen in the regenerated cervical tissue after excisional treatment for cervical intraepithelial neoplasia (CIN). Cohort study. A large tertiary teaching hospital in London. Women who underwent repeat excisional treatment for treatment failure or persistent CIN. Eligible women who underwent a repeat excisional treatment for treatment failure, including hysterectomy, between January 2002 and December 2007 in our colposcopy unit were identified by the Infoflex(®) database and SNOMED encoded histopathology database. Collagen expression was assessed using picro-Sirius red stain and the intensity of staining was compared in paired specimens from the first and second treatments. Differences in collagen expression were examined in the paired excisional treatment specimens. A total of 17 women were included. Increased collagen expression in the regenerated cervical tissue of the second cone compared with the first cone was noted in six women, decreased expression was noted in five women, and the pattern of collagen distribution was equivocal in six women. There is no overall change in collagen distribution during regeneration following excisional treatment for CIN. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

[Research on sexually transmitted infections in asymptomatic heterosexual males whose partners have cervical intraepithelial neoplasia].

PubMed

Varela, José A; Otero, Luis; Junquera, Maria Luisa; Melón, Santiago; del Valle, Asunción; Vázquez, Fernando

2006-06-01

Human papillomaviruses (HPV) are the etiological agents of genital warts and of cervical intraepithelial neoplasia (CIN), and they are sexually transmitted. The aim of this study is to determine the prevalence of sexually transmitted infections (STI) in asymptomatic heterosexual males who consult their physicians seeking advice after their partners have been diagnosed with CIN. 181 asymptomatic males whose partners were women diagnosed with CIN were studied at the STI unit in Gijón over a five-year period (1999-2003). The same diagnostic protocol was used in all cases: clinical exam, genitoscopy and the taking of samples for bacterial, fungus and Trichomonas cultures, as well as samples for the genomic detection of Chlamydia, and syphilis, HIV and viral hepatitis serology. 101 infections were diagnosed in 85 patients (47 %). By order of greatest prevalence, these were: urethritis from Ureaplasma urealyticum (35/181; 19.3 %), genital warts (31/181; 17.1 %), Haemophilus spp. (12 de 181; 6.6 %) and mycotic balanoposthitis (10/181; 5.5 %). The prevalence of STI in the partners of women with CIN is high, and in these cases it is necessary to establish STI detection and control programs in both members of the couple.

In vivo Diagnosis of Cervical Intraepithelial Neoplasia Using 337-nm- Excited Laser-Induced Fluorescence

NASA Astrophysics Data System (ADS)

Ramanujam, N.; Mitchell, M. F.; Mahadevan, A.; Warren, S.; Thomsen, S.; Silva, E.; Richards-Kortum, R.

1994-10-01

Laser-induced fluorescence at 337-nm excitation was used in vivo to differentiate neoplastic [cervical intraepithelial neoplasia (CIN)], nonneoplastic abnormal (inflammation and human papilloma viral infection), and normal cervical tissues. A colposcope (low-magnification microscope used to view the cervix with reflected light) was used to identify 66 normal and 49 abnormal (5 inflammation, 21 human papilloma virus infection, and 23 CIN) sites on the cervix in 28 patients. These sites were then interrogated spectroscopically. A two-stage algorithm was developed to diagnose CIN. The first stage differentiated histologically abnormal tissues from colposcopically normal tissues with a sensitivity, specificity, and positive predictive value of 92%, 90%, and 88%, respectively. The second stage differentiated preneoplastic and neoplastic tissues from nonneoplastic abnormal tissues with a sensitivity, specificity, and positive predictive value of 87%, 73%, and 74%, respectively. Spectroscopic differences were consistent with a decrease in the absolute contribution of collagen fluorescence, an increase in the absolute contribution of oxyhemoglobin attenuation, and an increase in the relative contribution of reduced nicotinamide dinucleotide phosphate [NAD(P)H] fluorescence as tissue progresses from normal to abnormal in the same patient. These results suggest that in vivo fluorescence spectroscopy of the cervix can be used to diagnose CIN at colposcopy.

Adverse Psychosexual Impact Related to the Treatment of Genital Warts and Cervical Intraepithelial Neoplasia

PubMed Central

Campaner, Adriana Bittencourt; Vespa Junior, Nelson; Giraldo, Paulo César; Leal Passos, Mauro Romero

2013-01-01

Objective. To compare the psychosexual impact related to the treatment of genital warts and cervical intraepithelial neoplasia (CIN) in women. Methods. 75 patients presenting with HPV-induced genital lesions, belonging to one of two patient groups, were included in the study: 29 individuals with genital warts (GWs) and 46 individuals with CIN grades 2 or 3 (CIN 2/3). Initially, medical charts of each woman were examined for extraction of data on the type of HPV-induced infection and treatment administered. Subjects were interviewed to collect sociodemographic data as well as personal, gynecologic, obstetric, and sexual history. After this initial anamnesis, the Sexual Quotient-Female Version (SQ-F) questionnaire was applied to assess sexual function. After application of the questionnaire, patients answered specific questions produced by the researchers, aimed at assessing the impact of the disease and its treatment on their sexual lives. Results. It is noteworthy that patients with CIN 2/3 had statistically similar classification of sexual quotient to patients with GWs (P = 0.115). However, patients with GWs more frequently gave positive answers to the specific questions compared to patients with CIN 2/3. Conclusion. Based on these findings, it is clear that GWs have a greater impact on sexual behavior compared to CIN 2/3. PMID:26316956

Evolution of terminology for human-papillomavirus-infection-related vulvar squamous intraepithelial lesions.

PubMed

Wilkinson, Edward J; Cox, J Thomas; Selim, Maria Angelica; O'Connor, Dennis M

2015-01-01

The aim of this study was to review the nearly 100-year evolution of terminology applicable to oncogenic human papillomavirus (HPV)-related vulvar intraepithelial squamous lesions and present current consensus terminology. An extensive literature search of the English language was performed, which included articles that reviewed French and German publications, from 1922 to 2012. The database search was assisted by representatives of the American Society for Colposcopy and the College of American Pathologists as part of a comprehensive study and consensus effort to achieve unified terminology among gynecologists, dermatologists, pathologists, and other related experts to develop for reporting female and male lower genital and anal HPV related squamous lesions. This was done by the committee referred to as the "LAST" Committee. Some of the results and conclusions have been previously presented and published. This presentation is specifically related to vulvar squamous intraepithelial lesion (SIL)/vulvar intraepithelial neoplasia terminology. This work will review past terminology related to HPV-related vulvar SIL, beginning in 1922. The most current terminology will be presented as proposed by the LAST Committee and considered by the World Health Organization this year in accord with the US-Canadian Academy of Pathology. A consensus of terminology for HPV-related vulvar SIL has been sought for some time, and currently, some consensus has been achieved. The term "squamous intraepithelial lesion" is favored over "intraepithelial neoplasia." A 2-tier classification, of "high grade (HSIL)" or "low grade (LSIL)," is favored over a 3- or 4-tier classification. The application of this terminology will be discussed.

The effectiveness of electrocautery ablation for the treatment of high-grade anal intraepithelial neoplasia in HIV-infected men who have sex with men.

PubMed

Burgos, J; Curran, A; Landolfi, S; Navarro, J; Tallada, N; Guelar, A; Crespo, M; Ocaña, I; Ribera, E; Falcó, V

2016-08-01

Electrocautery is one of the main treatment options for high-grade anal intraepithelial neoplasia (HGAIN). However, data regarding its efficacy are scarce. The aim of the study was to evaluate the effectiveness of electrocautery for the treatment of HGAIN. An observational study of HIV-infected men who have sex with men (MSM) who underwent screening for anal dysplasia was carried out. The on-treatment effectiveness of electrocautery was evaluated (according to biopsy findings measured 6-8 weeks after treatment) in patients with HGAIN. A complete response was defined as resolution of anal intraepithelial neoplasia (AIN), a partial response as regression to low-grade AIN and recurrence as biopsy-proven HGAIN during follow-up. From May 2009 to November 2014, 21.9% (126 of 576) of patients screened were found to have HGAIN. Electrocautery effectiveness was evaluated in 83 patients. A complete response was observed in 27 patients [32.5%; 95% confidence interval (CI) 23.4-53.2%], a partial response in 28 patients (33.7%; 95% CI 24.5-44.4%) and persistence in 28 patients (33.7%; 95% CI 24.5-44.4%). The patients with the most successful results (81.8%) required two to four sessions of electrocautery. After a mean follow-up of 12.1 months, 14 of 55 patients with a response (25.4%; 95% CI 15.8-38.3%) developed recurrent HGAIN within a mean time of 29.9 months (95% CI 22-37.7 months). No patient progressed to invasive cancer during the study or developed serious adverse events after treatment. No factors associated with poor response or recurrences were observed. Although electrocautery is the standard treatment for anal dysplasia, almost 50% of patients with HGAIN in our study did not respond or relapsed. New treatment strategies are necessary to optimize the management of anal dysplasia. © 2015 British HIV Association.

Clinical responses to focused ultrasound applied to women with vulval intraepithelial neoplasia.

PubMed

Jia, Ying; Wu, Jin; Xu, Man; Tang, Liangdan; Li, Chengzhi; Luo, Ming; Lou, Meng

2014-11-01

Focused ultrasound waves penetrate superficial tissues and are aimed toward the target tissues at specific depths to exert their biological effects. Focused ultrasound has been applied for a number of clinical indications, including vulval dystrophies and low-grade vulval disease. This study aimed to assess the efficacy and safety of focused ultrasound treatment of high-grade vulval intraepithelial neoplasia (VIN). Eighteen women with high-grade VIN were recruited and treated with focused ultrasound. During each posttreatment follow-up, the safety of, side effects of, and clinical responses to focused ultrasound were evaluated by a standardized protocol, including symptoms, clinical appearance, and histologic findings. All patients completed the designed follow-ups. In most cases, superficial mild to moderate swelling and blisters were seen in the focused ultrasound-treated skin but not in adjacent normal skin. Of the 18 patients, 16 showed complete histologic regression and resolution of symptoms 6 months after treatment. Of the other 2 patients, 1 showed complete regression after a second focused ultrasound treatment. The other patient did not respond to the focused ultrasound treatment and underwent a partial vulvectomy 6 months after treatment. None of the patients developed invasive carcinoma of the vulva during the follow-up period. One patient had local pruritus that was not alleviated by anti-inflammatory medication and local care. The complete responses observed in women with high-grade VIN treated by focused ultrasound, together with the preservation of adjacent normal tissue, suggest that focused ultrasound may be considered for treatment of high-grade VIN. © 2014 by the American Institute of Ultrasound in Medicine.

CO2 laser total superficial vulvectomy: an outpatient treatment for wide multifocal vulvar intraepithelial neoplasia grade 3.

PubMed

Fallani, Maria Grazia; Fambrini, Massimiliano; Lozza, Virginia; Bianchi, Claudia; Pieralli, Annalisa

2012-01-01

The ideal treatment of large multifocal vulvar intraepithelial neoplasia grade 3 (VIN 3) in young patients is still debated. The goal is to prevent development of invasive vulvar cancer while preserving normal vulvar anatomy and function. The authors describe the case of a 37-year-old woman affected by a biopsy-proven VIN 3 involving the entire external genitalia. A total superficial vulvectomy was carried out in 2 closer sessions by CO(2) laser used in an excisional way. Both procedures were performed in an outpatient setting with the patient under local anesthesia and without suturing stitches or skin flaps. Definitive pathologic analysis confirmed VIN 3 with free margins. No intraoperative and postoperative complications were documented. Functional and anatomic outcomes were optimal, and no relapse occurred after 12 months of follow-up. Use of CO(2) laser total superficial vulvectomy shows promise of a safe and adequate treatment in selected young patients with VIN 3 involving the entire external genitalia. Copyright © 2012 AAGL. Published by Elsevier Inc. All rights reserved.

Human papillomavirus DNA detection in menstrual blood from patients with cervical intraepithelial neoplasia and condyloma acuminatum.

PubMed

Wong, Sze Chuen Cesar; Au, Thomas Chi Chuen; Chan, Sammy Chung Sum; Chan, Charles Ming Lok; Lam, Money Yan Yee; Zee, Benny Chung Ying; Pong, Wei Mei; Chan, Anthony Tak Cheung

2010-03-01

The Papanicolaou test generates pain and embarrassment, and cytology screening has limited sensitivity for detection of cervical neoplasia. These factors urge the use of another screening test that can overcome these limitations. We explore a completely noninvasive method using detection of human papillomavirus (HPV) DNA in women's menstrual blood (MB). The participants were divided into 3 cohorts: (i) 235 patients with cervical intraepithelial neoplasia 3 (CIN 3) (n = 48), CIN 2 (n = 60), CIN 1 (n = 58), or condyloma acuminatum (CAC) (n = 69) before treatment or remission; (ii) from the first cohort of patients, 108 CIN 3 or CIN 2 patients after treatment and 62 CIN 1 or CAC patients after remission; and (iii) 323 apparently normal subjects (ANS) without any cervical disease. The HPV genotypes of the infected patients were confirmed by direct sequencing. Quantitative real-time PCR (QRT-PCR) was used to measure the MB HPV16 load for 15 infected patients. Results showed that the sensitivity, specificity, and positive and negative predictive values for detection of MB HPV DNA in samples from patients with CIN or CAC were 82.8%, 93.1%, 90.0%, and 87.9%, respectively. Moreover, MB HPV DNA was found in samples from 22.2% of CIN 3 or CIN 2 patients after treatment, 0.0% of CIN 1 or CAC patients after remission, and 8.1% of ANS, 4 of whom were found to have CIN 1 or CAC. Furthermore, QRT-PCR showed that the normalized MB HPV16 DNA copy numbers in samples from patients with CIN 1 to CIN 3 were significantly increased. These preliminary results suggested that MB HPV DNA is a potential noninvasive marker for these premalignant cervical diseases.

Concordance of gross surgical and final fixed margins in vulvar intraepithelial neoplasia 3 and vulvar cancer.

PubMed

DeSimone, Christopher P; Crisp, Meredith P; Ueland, Frederick R; DePriest, Paul D; van Nagell, John R; Lele, Subodh M; Modesitt, Susan C

2006-08-01

To prospectively evaluate the concordance of initial surgical vulvar margins and final fixed margins and to determine the amount of microscopic pathology of grossly negative margins in women with vulvar intraepithelial neoplasia (VIN) 3 or vulvar carcinoma. Women with VIN 3 or vulvar carcinoma undergoing surgical excision were identified. Prior to excision, acetic acid was used to highlight the lesions, and 2 sutures were placed, 1 at the edge of gross disease and another 1 cm distal from the first. After specimen removal and fixation, the distance between sutures and microscopic involvement of VIN was determined. Twenty-seven women were enrolled; however, only 19 had final fixed specimens that could be accurately measured. The median fixed distance of the vulvar margin was 0.85 cm (mean, 0.83; SD, 0.19) as compared to the gross, 1-cm margin (p = 0.001). Three subjects (16%) had microscopic involvement by VIN 3 in the grossly negative epithelium between the 2 sutures, but none had a positive peripheral margin. The gross surgical margin after vulvar resection is reduced by 15% when measured in its final fixed state, and a grossly negative 1-cm margin will seldom harbor significant disease.

Large contribution of human papillomavirus in vaginal neoplastic lesions: a worldwide study in 597 samples.

PubMed

Alemany, L; Saunier, M; Tinoco, L; Quirós, B; Alvarado-Cabrero, I; Alejo, M; Joura, E A; Maldonado, P; Klaustermeier, J; Salmerón, J; Bergeron, C; Petry, K U; Guimerà, N; Clavero, O; Murillo, R; Clavel, C; Wain, V; Geraets, D T; Jach, R; Cross, P; Carrilho, C; Molina, C; Shin, H R; Mandys, V; Nowakowski, A M; Vidal, A; Lombardi, L; Kitchener, H; Sica, A R; Magaña-León, C; Pawlita, M; Quint, W; Bravo, I G; Muñoz, N; de Sanjosé, S; Bosch, F X

2014-11-01

This work describes the human papillomavirus (HPV) prevalence and the HPV type distribution in a large series of vaginal intraepithelial neoplasia (VAIN) grades 2/3 and vaginal cancer worldwide. We analysed 189 VAIN 2/3 and 408 invasive vaginal cancer cases collected from 31 countries from 1986 to 2011. After histopathological evaluation of sectioned formalin-fixed paraffin-embedded samples, HPV DNA detection and typing was performed using the SPF-10/DNA enzyme immunoassay (DEIA)/LiPA25 system (version 1). A subset of 146 vaginal cancers was tested for p16(INK4a) expression, a cellular surrogate marker for HPV transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance. HPV DNA was detected in 74% (95% confidence interval (CI): 70-78%) of invasive cancers and in 96% (95% CI: 92-98%) of VAIN 2/3. Among cancers, the highest detection rates were observed in warty-basaloid subtype of squamous cell carcinomas, and in younger ages. Concerning the type-specific distribution, HPV16 was the most frequently type detected in both precancerous and cancerous lesions (59%). p16(INK4a) overexpression was found in 87% of HPV DNA positive vaginal cancer cases. HPV was identified in a large proportion of invasive vaginal cancers and in almost all VAIN 2/3. HPV16 was the most common type detected. A large impact in the reduction of the burden of vaginal neoplastic lesions is expected among vaccinated cohorts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Vulvar intraepithelial neoplasia with superficially invasive carcinoma of the vulva.

PubMed

Herod, J J; Shafi, M I; Rollason, T P; Jordan, J A; Luesley, D M

1996-05-01

To investigate the long-term outcome of patients presenting with vulvar intraepithelial neoplasia (VIN) with superficially invasive carcinoma of the vulva (SICa). A retrospective study using information obtained from patient case notes. Twenty-six women found at presentation to have VIN in association with superficially invasive carcinoma were identified during a 15-year period. Pruritus vulvae was the most frequent presenting symptom in 18 patients (69%). Sixteen women (61.5%) had multiple symptoms. Features noted at vulvar examination were variable and none were pathognomonic of either VIN or of superficial invasion. All patients had VIN 3 in association with a superficially invasive carcinoma. Histological changes associated with human papillomavirus were found in 19 (73%) women. Half had a co-existent or previous abnormality of the lower genital tract. Local excision was the most frequent initial treatment (n = 9 [35%]). Mean follow up time was 65 months (range 12-174). Disease persisted after primary treatment in five women (19%). Both histological recurrence (of either VIN or SICa) or symptomatic recurrence occurred in 10 patients (38%). All patients who experienced recurrence did so within 36 months of treatment. Overall, 12 patients (46%) relapsed (histological or symptomatic recurrence); the mean time was 18 months. Fourteen patients (54%) were managed satisfactorily by their initial treatment. One patient died of recurrent cervical cancer. Three progressed to frankly invasive disease: two (aged 31 and 39 years) with carcinoma of the vulva and one aged 34 years with carcinoma of the perianal margin. All are alive and well after treatment. One patient had recurrence of superficially invasive carcinoma treated by local excision with no further problems. No episode of metastasis via lymphatic or vascular channels has been seen. Patients with superficially invasive carcinoma of the vulva may be safely treated by local excisional methods without recourse to

[Nomenclature of squamous cell precursor lesions of the lower female genital tract : Current aspects].

PubMed

Horn, L-C; Brambs, C E; Handzel, R; Mehlhorn, G; Schmidt, D; Schierle, K

2016-11-01

The majority of precancerous lesions of the lower female genital tract (intraepithelial neoplasia, IN) are caused by human papillomavirus (HPV) infections resulting in cellular atypia and in turn an altered tissue architecture. Depending on the pathogenesis, a distinction is made between vulvar intraepithelial neoplasia (VIN) classified as classical VIN associated with high-risk HPV infections (u-VIN) and differentiated VIN (d-VIN), which is associated with lichen sclerosus et atrophicus and p53 alterations. In the current World Health Organization (WHO) classification a novel grading system for squamous cell precancerous lesions of the lower female genital tract has been proposed, differentiating low grade squamous intraepithelial lesions (L-SIL) including condyloma and HPV-associated alterations plus VIN 1, vaginal intraepithelial neoplasia (VaIN 1) and cervical intraepithelial neoplasia (CIN 1) from high grade squamous intraepithelial lesions (H-SIL) with VIN 2 and 3, VaIN 2 and 3 as well as CIN 2 and 3. The use of p16 immunohistochemistry can assist the differentiation. The new binary classification, however, contradicts the German cytological nomenclature (Munich nomenclature III), which differentiated three grades of dysplasia in order to avoid overtreatment of patients with moderate IN. The individual nomenclatures are compared to each other. It is recommended to report the grade of precancerous lesions in addition to the SIL classification of the WHO.

Clonal evolution in paired endometrial intraepithelial neoplasia/atypical hyperplasia and endometrioid adenocarcinoma.

PubMed

Russo, Mariano; Broach, James; Sheldon, Kathryn; Houser, Kenneth R; Liu, Dajiang J; Kesterson, Joshua; Phaeton, Rebecca; Hossler, Carrie; Hempel, Nadine; Baker, Maria; Newell, Jordan M; Zaino, Richard; Warrick, Joshua I

2017-09-01

Endometrial intraepithelial neoplasia (EIN) and atypical endometrial hyperplasia (AH) are histomorphologically defined precursors to endometrioid adenocarcinoma, which are unified as EIN/AH by the World Health Organization. EIN/AH harbors a constellation of molecular alterations similar to those found in endometrioid adenocarcinoma. However, the process of clonal evolution from EIN/AH to carcinoma is poorly characterized. To investigate, we performed next-generation sequencing, copy number alteration (CNA) analysis, and immunohistochemistry for mismatch repair protein expression on EIN/AH and endometrioid adenocarcinoma samples from 6 hysterectomy cases with spatially distinct EIN/AH and carcinoma. In evaluating all samples, EIN/AH and carcinoma did not differ in mutational burden, CNA burden, or specific genes mutated (all P>.1). All paired EIN/AH and carcinoma samples shared at least one identical somatic mutation, frequently in PI(3)K pathway members. Large CNAs (>10 genes in length) were identified in 83% of cases; paired EIN/AH and carcinoma samples shared at least one identical CNA in these cases. Mismatch repair protein expression matched in all paired EIN/AH and carcinoma samples. All paired EIN/AH and carcinoma samples had identical The Cancer Genome Atlas subtype, with 3 classified as "copy number low endometrioid" and 3 classified as "microsatellite instability hypermutated." Although paired EIN/AH and carcinoma samples were clonal, private mutations (ie, present in only one sample) were identified in EIN/AH and carcinoma in all cases, frequently in established cancer-driving genes. These findings indicate that EIN/AH gives rise to endometrioid adenocarcinoma by a complex process of subclone evolution, not a linear accumulation of molecular events. Copyright © 2017 Elsevier Inc. All rights reserved.

Medical interventions for high grade vulval intraepithelial neoplasia

PubMed Central

Pepas, Litha; Kaushik, Sonali; Bryant, Andrew; Nordin, Andy; Dickinson, Heather O

2014-01-01

Background Vulval intraepithelial neoplasia (VIN) is a pre-malignant condition of the vulval skin; its incidence is increasing in women under 50 years. VIN is graded histologically as low grade or high grade. High grade VIN is associated with infection with human papilloma virus (HPV) infection and may progress to invasive disease. There is no consensus on the optimal management of high grade VIN. The high morbidity and high relapse rate associated with surgical interventions call for a formal appraisal of the evidence available for less invasive but effective interventions for high grade VIN. Objectives To evaluate the effectiveness and safety of medical interventions for high grade VIN. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE (up to September 2010). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that assessed medical interventions, in adult women diagnosed with high grade VIN. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Where possible the data were synthesised in a meta-analysis. Main results Four trials met our inclusion criteria: three assessed the effectiveness of topical imiquimod versus placebo in women with high grade VIN; one examined low versus high dose indole-3-carbinol in similar women. Meta-analysis of three trials found that the proportion of women who responded to treatment at 5 to 6 months was much higher in the group who received topical imiquimod than in the group who received placebo (relative risk (RR) = 11.95, 95% confidence interval (CI) 3.21 to 44.51). A single trial showed similar results at 12 months in (RR = 9.10, 95% CI 2.38 to 34.77). Only one trial reported

ThinPrep Pap-smear and cervical intraepithelial neoplasia in reproductive-aged Thai women.

PubMed

Rugpao, S; Koonlertkit, S; Ruengkrist, T; Lamlertkittikul, S; Pinjaroen, S; Limtrakul, A; Werawatakul, Y; Sinchai, W

2009-06-01

To estimate the incidence of abnormal cervical cytology by ThinPrep Pap-tests and cervical intraepithelial neoplasia (CIN) in young adult reproductive-aged Thai women. A total of 1254 women distributed in all regions of Thailand were monitored from 2002 through 2004. Women were screened for abnormal cervical cytology using the ThinPrep method every 6 months. Interpretation of cervical cytology was based on the Bethesda system, version 2001. Women who had the ThinPrep Pap results as atypical squamous cells of undetermined significance or worse underwent colposcopic examination. The ThinPrep and all cervical tissue samples obtained from diagnostic or therapeutic procedures were analyzed and reviewed by Covance Central Laboratory Service, Inc., Indianapolis, USA. The cumulative incidence of abnormal ThinPrep Pap-tests was as follows: 15.3 per 100 woman years (WY) (95% confidence interval [CI] 12.3, 18.9) at 6 months; 12.3 per 100 WY (95% CI 10.3, 14.6) at 12 months; and 11.6 per 100 WY (95% CI 10.0, 13.5) at 18 months. Of 1448.6 woman years of follow up, the incidence of CIN1 was 4.1 per 100 WY (95% CI 3.2, 5.3); CIN2 0.8 per 100 WY (95% CI 0.4, 1.4); and CIN3 0.6 per 100 WY (95% CI 0.3, 1.2). The incidence of abnormal ThinPrep Pap-test and CIN in young adult Thai women had been reported. No comparable data is available.

Human Papillomavirus DNA Detection in Menstrual Blood from Patients with Cervical Intraepithelial Neoplasia and Condyloma Acuminatum ▿

PubMed Central

Wong, Sze Chuen Cesar; Au, Thomas Chi Chuen; Chan, Sammy Chung Sum; Chan, Charles Ming Lok; Lam, Money Yan Yee; Zee, Benny Chung Ying; Pong, Wei Mei; Chan, Anthony Tak Cheung

2010-01-01

The Papanicolaou test generates pain and embarrassment, and cytology screening has limited sensitivity for detection of cervical neoplasia. These factors urge the use of another screening test that can overcome these limitations. We explore a completely noninvasive method using detection of human papillomavirus (HPV) DNA in women's menstrual blood (MB). The participants were divided into 3 cohorts: (i) 235 patients with cervical intraepithelial neoplasia 3 (CIN 3) (n = 48), CIN 2 (n = 60), CIN 1 (n = 58), or condyloma acuminatum (CAC) (n = 69) before treatment or remission; (ii) from the first cohort of patients, 108 CIN 3 or CIN 2 patients after treatment and 62 CIN 1 or CAC patients after remission; and (iii) 323 apparently normal subjects (ANS) without any cervical disease. The HPV genotypes of the infected patients were confirmed by direct sequencing. Quantitative real-time PCR (QRT-PCR) was used to measure the MB HPV16 load for 15 infected patients. Results showed that the sensitivity, specificity, and positive and negative predictive values for detection of MB HPV DNA in samples from patients with CIN or CAC were 82.8%, 93.1%, 90.0%, and 87.9%, respectively. Moreover, MB HPV DNA was found in samples from 22.2% of CIN 3 or CIN 2 patients after treatment, 0.0% of CIN 1 or CAC patients after remission, and 8.1% of ANS, 4 of whom were found to have CIN 1 or CAC. Furthermore, QRT-PCR showed that the normalized MB HPV16 DNA copy numbers in samples from patients with CIN 1 to CIN 3 were significantly increased. These preliminary results suggested that MB HPV DNA is a potential noninvasive marker for these premalignant cervical diseases. PMID:20089764

Interleukin-10 gene -1082 G/A polymorphism in cervical cancer and cervical intraepithelial neoplasia: meta-analysis.

PubMed

Zhang, Shuo; Kong, Ya-Lin; Li, Ya-Li; Yin, Yan-Wei

2014-12-01

To assess the association between polymorphism in the interleukin (IL)-10 promoter region of 1082 G/A and the risk of cervical cancer and/or cervical intraepithelial neoplasia (CIN), using meta-analysis. The electronic literature databases PubMed®, Embase®, Web of Science, CBMdisc and CNKI were searched for relevant studies. The strength of association between IL-10 gene -1082 G/A polymorphism and cervical cancer and/or CIN was measured using pooled odds ratios with 95% confidence intervals in four genetic models: allelic model (A allele versus G allele); additive model (A/A versus G/G); recessive model (A/A versus G/A+G/G); dominant model (A/A+G/A versus G/G). Eight studies involving 1983 cases and 1618 controls were identified and included in the meta-analysis. No significant associations were found between IL-10 gene -1082 G/A polymorphism and cervical cancer and/or CIN in any of the genetic models. IL-10 gene -1082 G/A polymorphism does not appear to be associated with the risk of cervical cancer and/or CIN. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Vulvar Cancer—Health Professional Version

Cancer.gov

Vulvar cancer forms in a woman's external genitalia, and most often affects the outer vaginal lips. Having vulvar intraepithelial neoplasia or HPV infection can affect the risk of vulvar cancer. Find evidence-based information on vulvar cancer treatment, research, and statistics.

An intelligent clinical decision support system for patient-specific predictions to improve cervical intraepithelial neoplasia detection.

PubMed

Bountris, Panagiotis; Haritou, Maria; Pouliakis, Abraham; Margari, Niki; Kyrgiou, Maria; Spathis, Aris; Pappas, Asimakis; Panayiotides, Ioannis; Paraskevaidis, Evangelos A; Karakitsos, Petros; Koutsouris, Dimitrios-Dionyssios

2014-01-01

Nowadays, there are molecular biology techniques providing information related to cervical cancer and its cause: the human Papillomavirus (HPV), including DNA microarrays identifying HPV subtypes, mRNA techniques such as nucleic acid based amplification or flow cytometry identifying E6/E7 oncogenes, and immunocytochemistry techniques such as overexpression of p16. Each one of these techniques has its own performance, limitations and advantages, thus a combinatorial approach via computational intelligence methods could exploit the benefits of each method and produce more accurate results. In this article we propose a clinical decision support system (CDSS), composed by artificial neural networks, intelligently combining the results of classic and ancillary techniques for diagnostic accuracy improvement. We evaluated this method on 740 cases with complete series of cytological assessment, molecular tests, and colposcopy examination. The CDSS demonstrated high sensitivity (89.4%), high specificity (97.1%), high positive predictive value (89.4%), and high negative predictive value (97.1%), for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In comparison to the tests involved in this study and their combinations, the CDSS produced the most balanced results in terms of sensitivity, specificity, PPV, and NPV. The proposed system may reduce the referral rate for colposcopy and guide personalised management and therapeutic interventions.

An Intelligent Clinical Decision Support System for Patient-Specific Predictions to Improve Cervical Intraepithelial Neoplasia Detection

PubMed Central

Bountris, Panagiotis; Haritou, Maria; Pouliakis, Abraham; Margari, Niki; Kyrgiou, Maria; Spathis, Aris; Pappas, Asimakis; Panayiotides, Ioannis; Paraskevaidis, Evangelos A.; Karakitsos, Petros; Koutsouris, Dimitrios-Dionyssios

2014-01-01

Nowadays, there are molecular biology techniques providing information related to cervical cancer and its cause: the human Papillomavirus (HPV), including DNA microarrays identifying HPV subtypes, mRNA techniques such as nucleic acid based amplification or flow cytometry identifying E6/E7 oncogenes, and immunocytochemistry techniques such as overexpression of p16. Each one of these techniques has its own performance, limitations and advantages, thus a combinatorial approach via computational intelligence methods could exploit the benefits of each method and produce more accurate results. In this article we propose a clinical decision support system (CDSS), composed by artificial neural networks, intelligently combining the results of classic and ancillary techniques for diagnostic accuracy improvement. We evaluated this method on 740 cases with complete series of cytological assessment, molecular tests, and colposcopy examination. The CDSS demonstrated high sensitivity (89.4%), high specificity (97.1%), high positive predictive value (89.4%), and high negative predictive value (97.1%), for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+). In comparison to the tests involved in this study and their combinations, the CDSS produced the most balanced results in terms of sensitivity, specificity, PPV, and NPV. The proposed system may reduce the referral rate for colposcopy and guide personalised management and therapeutic interventions. PMID:24812614

Systematic review of guidelines for the assessment and management of high-grade anal intraepithelial neoplasia (AIN II/III).

PubMed

Alam, N N; White, D A; Narang, S K; Daniels, I R; Smart, N J

2016-02-01

There is ambiguity with regard to the optimal management of anal intraepithelial neoplasia (AIN) III. The aim of this review was to assess and compare international/national society guidelines currently available in the literature on the management, treatment and surveillance of AIN III. We also aimed to assess the quality of the studies used to compile the guidelines and to clarify the terminology used in histological assessment. An electronic search of PubMed and Embase was performed using the search terms 'anal intraepithelial neoplasia', 'AIN', 'anal cancer', 'guidelines', 'surveillance' and 'management'. Literature reviews and guidelines or practice guidelines in peer reviewed journals from 1 January 2000 to 31 December 2014 assessing the treatment, surveillance or management of patients with AIN related to human papilloma virus were included. The guidelines identified by the search were assessed for the quality of evidence behind them using the Oxford Centre for Evidence-based Medicine 2011 Levels of Evidence. The database search identified 5159 articles and two further guidelines were sourced from official body guidelines. After inclusion criteria were applied, 28 full-text papers were reviewed. Twenty-five of these were excluded, leaving three guidelines for inclusion in the systematic review: those published by the Association of Coloproctology of Great Britain and Ireland, the American Society of Colon and Rectal Surgeons and the Italian Society of Colorectal Surgery. No guidelines were identified on the management of AIN III from human papilloma virus associations and societies. All three guidelines agree that a high index of clinical suspicion is essential for diagnosing AIN with a disease-specific history, physical examination, digital rectal examination and anal cytology. There is interchange of terminology from high-grade AIN (HGAIN) (which incorporates AIN II/III) and AIN III in the literature leading to confusion in therapy use. Treatment varies

Quantification of confocal fluorescence microscopy for the detection of cervical intraepithelial neoplasia.

PubMed

Sheikhzadeh, Fahime; Ward, Rabab K; Carraro, Anita; Chen, Zhao Yang; van Niekerk, Dirk; Miller, Dianne; Ehlen, Tom; MacAulay, Calum E; Follen, Michele; Lane, Pierre M; Guillaud, Martial

2015-10-24

Cervical cancer remains a major health problem, especially in developing countries. Colposcopic examination is used to detect high-grade lesions in patients with a history of abnormal pap smears. New technologies are needed to improve the sensitivity and specificity of this technique. We propose to test the potential of fluorescence confocal microscopy to identify high-grade lesions. We examined the quantification of ex vivo confocal fluorescence microscopy to differentiate among normal cervical tissue, low-grade Cervical Intraepithelial Neoplasia (CIN), and high-grade CIN. We sought to (1) quantify nuclear morphology and tissue architecture features by analyzing images of cervical biopsies; and (2) determine the accuracy of high-grade CIN detection via confocal microscopy relative to the accuracy of detection by colposcopic impression. Forty-six biopsies obtained from colposcopically normal and abnormal cervical sites were evaluated. Confocal images were acquired at different depths from the epithelial surface and histological images were analyzed using in-house software. The features calculated from the confocal images compared well with those features obtained from the histological images and histopathological reviews of the specimens (obtained by a gynecologic pathologist). The correlations between two of these features (the nuclear-cytoplasmic ratio and the average of three nearest Delaunay-neighbors distance) and the grade of dysplasia were higher than that of colposcopic impression. The sensitivity of detecting high-grade dysplasia by analysing images collected at the surface of the epithelium, and at 15 and 30 μm below the epithelial surface were respectively 100, 100, and 92 %. Quantitative analysis of confocal fluorescence images showed its capacity for discriminating high-grade CIN lesions vs. low-grade CIN lesions and normal tissues, at different depth of imaging. This approach could be used to help clinicians identify high-grade CIN in clinical

Local Lymphocytes and Nitric Oxide Synthase in the Uterine Cervical Stroma of Patients with Grade III Cervical Intraepithelial Neoplasia

PubMed Central

da Silva, Cléber Sergioda; Michelin, Marcia Antoniazi; Etchebehere, Renata Margarida; Adad, Sheila Jorge; Murta, Eddie Fernando Candido

2010-01-01

OBJECTIVES: Precancerous and cancerous cells can trigger an immune response that may limit tumor development and can be used as a prognostic marker. The aims of the present study were to quantify the presence of B and T lymphocytes, macrophages and cells expressing inducible nitric oxide synthase (iNOS) in the cervical stroma of women with grade III cervical intraepithelial neoplasia (CIN III) or in the intratumoral and peritumoral tissue of women with stage I invasive carcinoma. METHODS: Cervical tissue specimens were obtained from 60 women (20 each from control tissues, CIN III and invasive carcinomas). The average ages in the control, CIN III and invasive groups were 43.9 (± 4.3), 35.5 (± 9.5), and 50 (± 11.2) years, respectively. The specimens were immunohistochemically labeled with antibodies to identify T lymphocytes (CD3), cytotoxic lymphocytes (CD8), B lymphocytes (CD20), macrophages (CD68) and iNOS. We evaluated the markers in the stroma above the squamocolumnar junction (control), at the intraepithelial lesion (CIN cases), and in the nfiltrating tumor. Two independent observers performed the immunohistochemical analysis. RESULTS: T lymphocytes, B lymphocytes, macrophages and iNOS were present more frequently (P<0.05) in the stroma of peritumoral invasive tumors compared to the controls and intratumoral invasive cancer samples. CD3+ and CD20+ lymphocytes were present more frequently in CIN III patients compared to samples from patients with intratumoral invasive cancer (P<0.05). CONCLUSION: High numbers of T and B lymphocytes, macrophages and iNOS-expressing cells in the peritumoral stroma of the invasive tumors were observed. Cell migration appeared to be proportional to the progression of the lesion. PMID:20613932

The contribution of MIB 1 in the accurate grading of vulvar intraepithelial neoplasia.

PubMed

van Beurden, M; de Craen, A J; de Vet, H C; Blaauwgeers, J L; Drillenburg, P; Gallee, M P; de Kraker, N W; Lammes, F B; ten Kate, F J

1999-11-01

To determine the interobserver variation in scoring presence and grade of vulvar intraepithelial neoplasia (VIN) in haematoxylin/eosin (H/E) slides, MIB 1 slides, and the combined use of H/E and MIB 1 slides. 10 slides were stained with H/E and MIB 1 with each of the following diagnoses: normal vulvar skin, VIN 1, VIN 2, and VIN 3. Six observers first scored the H/E slides separately from the MIB 1 slides and second the combined H/E and MIB 1 slides. Unweighted group kappa for MIB 1 was 0.62 and the weighted group kappa was 0.91. This was significantly better than the unweighted group kappa for H/E slides (0.47, p = 0.023) as well as the weighted group kappa for H/E slides (0.82, p = 0.014). There was no improvement by the combined use of H/E and MIB 1 slides. VIN 2 is far less confused with VIN 3 in the combined use of H/E and MIB 1 slides (9%) than in H/E slides (38%) (p = 0.007). There is a tendency to grade VIN in a two tailed grading system rather than a three tailed grading system, which became more apparent with the combined use of H/E and MIB 1 slides. The interobserver variation with sole use of MIB 1 is better than with the use of H/E stain in VIN. The use of MIB 1 in grading VIN diminishes confusion between VIN 2 and VIN 3 fourfold. A two tailed grading system for VIN seems already to work in daily practice.

The contribution of MIB 1 in the accurate grading of vulvar intraepithelial neoplasia.

PubMed Central

van Beurden, M; de Craen, A J; de Vet, H C; Blaauwgeers, J L; Drillenburg, P; Gallee, M P; de Kraker, N W; Lammes, F B; ten Kate, F J

1999-01-01

AIM: To determine the interobserver variation in scoring presence and grade of vulvar intraepithelial neoplasia (VIN) in haematoxylin/eosin (H/E) slides, MIB 1 slides, and the combined use of H/E and MIB 1 slides. METHODS: 10 slides were stained with H/E and MIB 1 with each of the following diagnoses: normal vulvar skin, VIN 1, VIN 2, and VIN 3. Six observers first scored the H/E slides separately from the MIB 1 slides and second the combined H/E and MIB 1 slides. RESULTS: Unweighted group kappa for MIB 1 was 0.62 and the weighted group kappa was 0.91. This was significantly better than the unweighted group kappa for H/E slides (0.47, p = 0.023) as well as the weighted group kappa for H/E slides (0.82, p = 0.014). There was no improvement by the combined use of H/E and MIB 1 slides. VIN 2 is far less confused with VIN 3 in the combined use of H/E and MIB 1 slides (9%) than in H/E slides (38%) (p = 0.007). There is a tendency to grade VIN in a two tailed grading system rather than a three tailed grading system, which became more apparent with the combined use of H/E and MIB 1 slides. CONCLUSIONS: The interobserver variation with sole use of MIB 1 is better than with the use of H/E stain in VIN. The use of MIB 1 in grading VIN diminishes confusion between VIN 2 and VIN 3 fourfold. A two tailed grading system for VIN seems already to work in daily practice. Images PMID:10690171

A Systematic Review of the Prevalence and Attribution of Human Papillomavirus Types Among Cervical, Vaginal and Vulvar Pre-cancers and Cancers in the United States

PubMed Central

Insinga, Ralph P.; Liaw, Kai-Li; Johnson, Lisa G.; Madeleine, Margaret M.

2008-01-01

Objectives To describe (1) prevalence and (2) estimated attribution of human papillomavirus (HPV) types in U.S. cervical, vaginal and vulvar precancers and cancers. Methods U.S. studies reporting HPV typing for cervical (CIN), vulvar (VIN) and vaginal (VaIN) intraepithelial neoplasias and/or invasive cancers of those sites were gathered from the PubMed database (http://www.ncbi.nlm.nih.gov/sites/entrez/). Selected studies had polymerase chain reaction testing data for ≥10 cases for a disease endpoint. Analytic methods augmented prior reviews of cervical disease with an updated and expanded analysis (including vulvar and vaginal disease), new selection criteria for specimens, and adjustment for histologic type, where possible, among pooled cancer cases. In addition, for analyses of estimated attribution of HPV types, we incorporated accounting methods for lesions infected with multiple HPV types. Results Data from 22 U.S. studies meeting review eligibility criteria were tabulated. Following adjustment for the presence of multiple HPV types in a single specimen, the top two HPV types contributing to disease were: CIN 1 (HPV 16/66) [15.3%], CIN 2/3 (16/31) [61.9%], cervical cancer (16/18) [79.2%], VIN 1 (6/11) [41.7%], VIN 3 (16/18) [84.0%], vulvar cancer (16/33) [55.5%], VaIN 3 (16/18) [65.1%], vaginal cancer (16/18) [72.7%]. Conclusions The HPV type distribution and proportion of cases testing positive for any HPV type were observed to vary among U.S. cervical, vulvar and vaginal neoplasias and by grade of disease. Adjustment for the presence of multi-type HPV infections can have an important impact on the estimated attribution of HPV types to disease, particularly for types other than HPV 16. PMID:18628412

An S100P-positive biliary epithelial field is a preinvasive intraepithelial neoplasm in nodular-sclerosing cholangiocarcinoma.

PubMed

Nakanuma, Yasuni; Uchida, Tsuneyuki; Sato, Yasunori; Uesaka, Katsuhiko

2017-02-01

Nodular-sclerosing cholangiocarcinoma (NS-CCA) is a common CCA of the intrahepatic large, perihilar, and distal bile ducts. Intraepithelial biliary neoplasms, such as the mucosal extension of carcinoma and preinvasive neoplastic lesions (ie, biliary intraepithelial neoplasia) reportedly occur in the bile ducts around CCA. In the present study, we collectively refer to these intraepithelial lesions as "intraepithelial neoplasms of the bile duct (IENBs)". We examined the IENBs in 57 surgically resected cases of NS-CCA. S100P immunostaining was used to help detect IENBs. The IENBs formed field(s) of continuous neoplastic biliary epithelial cells and showed a flat, micropapillary, or papillotubular configuration. IENBs could be classified into 3 categories based on their atypia: group A (neoplastic but not enough for malignancy), B (neoplastic and sufficiently well differentiated for high-grade dysplasia), and C (overtly malignant and variably differentiated). IENB was found in 31 of 57 cases, with group C the most common (26 cases) followed by group B (22 cases) and group A (16 cases). The expression of cancer-related molecules and MIB-1 index of groups A and B differed from those of invasive CCA, whereas these features of group C were relatively similar to those of invasive CCA. In conclusion, IENB was not infrequently found in NS-CCA and could be classified into 3 grades. Preinvasive lesions (biliary intraepithelial neoplasias) are likely to be found in groups A and B, whereas cancerization would be included in group C. The classification of IENB may be useful for future studies of the preinvasive intraepithelial neoplastic lesions of NS-CCAs. Copyright © 2016. Published by Elsevier Inc.

Association of Human Papillomavirus 31 DNA Load with Risk of Cervical Intraepithelial Neoplasia Grades 2 and 3

PubMed Central

Liu, Xia; Schiffman, Mark; Hulbert, Ayaka; He, Zhonghu; Shen, Zhenping; Koutsky, Laura A.

2015-01-01

The association between human papillomavirus 31 (HPV31) DNA loads and the risk of cervical intraepithelial neoplasia grades 2 and 3 (CIN2–3) was evaluated among women enrolled in the atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) triage study (ALTS), who were monitored semiannually over 2 years and who had HPV31 infections detected at ≥1 visit. HPV31 DNA loads in the first HPV31-positive samples and in a random set of the last positive samples from women with ≥2 HPV31-positive visits were measured by a real-time PCR assay. CIN2–3 was histologically confirmed at the same time as the first detection of HPV31 for 88 (16.6%) of 530 women. After adjustment for HPV31 lineages, coinfection with other oncogenic types, and the timing of the first positive detection, the odds ratio (OR) per 1-log-unit increase in viral loads for the risk of a concurrent diagnosis of CIN2–3 was 1.5 (95% confidence interval [CI], 1.2 to 1.9). Of 373 women without CIN2–3 at the first positive visit who had ≥1 later visit, 44 had subsequent diagnoses of CIN2–3. The initial viral loads were associated with CIN2–3 diagnosed within 6 months after the first positive visit (adjusted OR, 1.5 [95% CI, 1.0 to 2.4]) but were unrelated to CIN2–3 diagnosed later. For a random set of 49 women who were tested for viral loads at the first and last positive visits, changes in viral loads were upward and downward among women with and without follow-up CIN2–3 diagnoses, respectively, although the difference was not statistically significant. Results suggest that HPV31 DNA load levels at the first positive visit signal a short-term but not long-term risk of CIN2–3. PMID:26292291

Review: Anal Intraepithelial Neoplasia in HIV-Infected Men Who Have Sex with Men: Is Screening and Treatment Justified?

PubMed

Wasserman, Peter; Rubin, David S; Turett, Glenn

2017-06-01

Anal squamous cell carcinoma (SCC) is the fourth most prevalent cancer in human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). Human papillomavirus (HPV) has been detected in over 90% of anal carcinoma biopsy specimens from MSM, and is considered a necessary, but alone, insufficient factor for carcinogenesis. Anal intraepithelial neoplasia (AIN) may be precursive for SCC, and screening cytology with referral of persons with abnormality for high-resolution anoscopy-guided biopsy, and AIN treatment, has been recommended for prevention. In the absence of either randomized controlled trials or surveillance data demonstrating a reduction in anal SCC incidence, these recommendations were based on analogy with cervical cancer. HPV-mediated genetic changes associated with cervical cancer, and aneuploidy, have been documented in AIN. However, little data exist on the rate of AIN progression to SCC. The treatment of AIN is frequently prolonged and not curative, and if routinized in the care of HIV-infected MSM, would likely be recurring well into their sixth decade of life. Clinical trials demonstrating a reduction in invasive anal carcinoma incidence, as well as acceptable morbidity with repeated AIN destruction, are needed before asking our patients to commit to routine treatment.

A large, population-based study of age-related associations between vaginal pH and human papillomavirus infection.

PubMed

Clarke, Megan A; Rodriguez, Ana Cecilia; Gage, Julia C; Herrero, Rolando; Hildesheim, Allan; Wacholder, Sholom; Burk, Robert; Schiffman, Mark

2012-02-08

Vaginal pH is related to genital tract inflammation and changes in the bacterial flora, both suggested cofactors for persistence of human papillomavirus (HPV) infection. To evaluate the relationship between vaginal pH and HPV, we analyzed data from our large population-based study in Guanacaste, Costa Rica. We examined vaginal pH and the risk of HPV infection, cytological abnormalities, and C. trachomatis infection. Our study included 9,165 women aged 18-97 at enrollment with a total of 28,915 visits (mean length of follow-up = 3.4 years). Generalized estimating equations were used to evaluate the relationship between vaginal pH and HPV infection (both overall and single versus multiple types) and low-grade squamous intraepithelial lesions (LSIL), the cytomorphic manifestation of HPV infection. The relationship between enrollment vaginal pH and C. trachomatis infection was assessed by logistic regression. Results were stratified by age at visit. Detection of HPV was positively associated with vaginal pH, mainly in women < 35 years (p-trend = 0.009 and 0.007 for women aged < 25 and 25-34 years, respectively). Elevated vaginal pH was associated with 30% greater risk of infection with multiple HPV types and with LSIL, predominantly in women younger than 35 and 65+ years of age. Detection of C. trachomatis DNA was associated with increased vaginal pH in women < 25 years (OR 2.2 95% CI 1.0-5.0). Our findings suggest a possible association of the cervical microenvironment as a modifier of HPV natural history in the development of cervical precancer and cancer. Future research should include studies of vaginal pH in a more complex assessment of hormonal changes and the cervicovaginal microbiome as they relate to the natural history of cervical neoplasia.

Prevalence of cervical intraepithelial neoplasia grades II/III and cervical cancer in patients with cytological diagnosis of atypical squamous cells when high-grade intraepithelial lesions (ASC-H) cannot be ruled out.

PubMed

Cytryn, Andréa; Russomano, Fábio Bastos; Camargo, Maria José de; Zardo, Lucília Maria Gama; Horta, Nilza Maria Sobral Rebelo; Fonseca, Rachel de Carvalho Silveira de Paula; Tristão, Maria Aparecida; Monteiro, Aparecida Cristina Sampaio

2009-09-01

The latest update of the Bethesda System divided the category of atypical squamous cells of undetermined significance (ASCUS) into ASC-US (undetermined significance) and ASC-H (high-grade intraepithelial lesion cannot be ruled out). The aims here were to measure the prevalence of pre-invasive lesions (cervical intraepithelial neoplasia, CIN II/III) and cervical cancer among patients referred to Instituto Fernandes Figueira (IFF) with ASC-H cytology, and compare them with ASC-US cases. Cross-sectional study with retrospective data collection, at the IFF Cervical Pathology outpatient clinic. ASCUS cases referred to IFF from November 1997 to September 2007 were reviewed according to the 2001 Bethesda System to reach cytological consensus. The resulting ASC-H and ASC-US cases, along with new cases, were analyzed relative to the outcome of interest. The histological diagnosis (or cytocolposcopic follow-up in cases without such diagnosis) was taken as the gold standard. The prevalence of CIN II/III in cases with ASC-H cytology was 19.29% (95% confidence interval, CI, 9.05-29.55%) and the risk of these lesions was greater among patients with ASC-H than with ASC-US cytology (prevalence ratio, PR, 10.42; 95% CI, 2.39-45.47; P = 0.0000764). Pre-invasive lesions were more frequently found in patients under 50 years of age with ASC-H cytology (PR, 2.67; 95% CI, 0.38-18.83); P = 0.2786998). There were no uterine cervical cancer cases. The prevalence of CIN II/III in patients with ASC-H cytology was significantly higher than with ASC-US, and division into ASC diagnostic subcategories had good capacity for discriminating the presence of pre-invasive lesions.

Diagnostic performance of HPV E6/E7 mRNA assay for detection of cervical high-grade intraepithelial neoplasia and cancer among women with ASCUS Papanicolaou smears.

PubMed

Ren, Chenchen; Zhu, Yuanhang; Yang, Li; Zhang, Xiaoan; Liu, Ling; Ren, Chunying

2018-02-01

The aim of this study was to investigate the clinical performance of high risk (HR) HPV E6/E7 mRNA assay in detecting cervical high-grade intraepithelial neoplasia and cancer among women with atypical squamous cells of undetermined significance (ASCUS) Papanicolaou (Pap) smears. A total of 160 patients with ASCUS who underwent HR-HPV DNA assay, HR-HPV E6/E7 mRNA assay and colposcopy biopsy at Third Affiliated Hospital of Zhengzhou University, China, from December 2015 to March 2017, were enrolled. Logistic regression analysis was used to evaluate the relationship between pathological results with clinical biologic factors. Univariate analysis showed that the qualitative results of HR-HPV DNA, qualitative results of HR-HPV E6/E7 mRNA and expression levels of HR-HPV E6/E7 mRNA were risk factors of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer (all P < 0.05). Multivariable analysis found that only the expression levels of HR-HPV E6/E7 mRNA was associated with high-grade CIN and cervical cancer (OR = 8.971, 95% CI = 2.572-31.289, P = 0.001). An optimal cut-off value of ≥ 558.26 copies/ml was determined using receiver operating characteristic curve, and specificity of cut-off value were higher than E6/E7 mRNA qualitative assay and DNA qualitative assay. HPV E6/E7 mRNA quantitative assay may be a valuable tool in triage of ASCUS pap smears. A high specificity of E6/E7 mRNA quantitative assay as a triage test in women with ASCUS can be translated into a low referral for colposcopy.

[Human papillomavirus infection and cervical intraepithelial neoplasia morbidity of women from different occupations in Shenzhen city, China].

PubMed

Tang, Hui-ru; Zhou, Yan-qiu; Wu, Lan-na; Liu, Zhi-hong; Zhang, Li-jie; Wu, Rui-fang

2007-10-01

To investigate the human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) morbidity of women from different occupations in Shenzhen city. 2045 women of five kinds of occupation in Shenzhen city, including 130 teachers, 385 workers, 316 service women, 199 poverish women, 420 doctors or nurses and 595 general residents were included. We screened these women by methods of detecting high risk HPV of hc2 combing with LCT. Women with screening positive results were diagnosed CIN by colposcopic biopsy. (1) High risk factors on HPV infection rate in different occupations were different with the highest in service occupation (19.3%) while the lowest appeared in medical workers (11.9%). (2) In those 2045 women, we found 199 cervical lesions including pathological HPV infection, CIN1, 2, 3 and cervical cancers, with morbidity rates as 4.11%, 3.28%, 1.67%, 0.54% and 0.15% respectively. Along with the progress of the cervical lesions, the morbidity decreased. (3) The morbidity rates of CIN in different occupations were different, with the highest of HSIL in service occupation and the lowest in teachers. Women of different occupations in Shenzhen city had different high risk HPV infection rates and CIN morbidity. The HPV infection rate and HSIL morbidity were highest among women having service related jobs.

Prevalence of High-Grade Intraepithelial Neoplasia in Patients with Cytology Presenting Atypical Squamous Cells of Undetermined Significance.

PubMed

Marcos Lopes, Ana Cristina; Campaner, Adriana Bittencourt; Henrique, Laílca Quirino

2016-01-01

To evaluate the prevalence of histological high-grade lesions and cervical cancer in patients with ASCUS cytology. This is a cross-sectional prospective study involving 703 women with a uterus and atypical squamous cells of undetermined significance (ASCUS). The patients were submitted to a colposcopy and underwent a guided biopsy when changes on the colposcopy were detected. The findings revealed 456 (64.9%) women with a normal colposcopy and 247 (35.1%) with colposcopic abnormalities. The biopsy results were: cervical intraepithelial neoplasia grade 1 (CIN 1) in 51 (20.6%) patients, CIN 2 in 11 (4.5%) patients, CIN 3 in 8 (3.2%) patients, and a negative result in 177 (71.7%) patients; no cases of cancer were detected. Tallying of 456 normal colposcopies and 177 negative biopsies yielded a total of 90.04% negative exams. Furthermore, around 7.2% (51/703) of the patients exhibited CIN 1, a lesion associated with a high potential for regression. The biopsy results were not associated with patient age or menopausal status. We conclude that cytological surveillance of patients with ASCUS is feasible and safe given the low risk of CIN 2/3 or cervical cancer. © 2016 S. Karger AG, Basel.

Topical hexaminolevulinate photodynamic therapy for the treatment of persistent human papilloma virus infections and cervical intraepithelial neoplasia.

PubMed

Hillemanns, Peter; Einstein, Mark H; Iversen, Ole Erik

2015-02-01

Current treatments for high-grade cervical intraepithelial neoplasia (CIN2/3) are mainly excisional procedures, which are associated with significant side effects and pose risks for future pregnancies. An effective and safe therapy is needed to reduce the requirement for surgical interventions in women of reproductive age. This review looks at the pharmacokinetic and clinical data for topical hexaminolevulinate (HAL) photodynamic therapy (PDT), which is currently entering late phase clinical trials for high-grade CIN. The authors include published studies in patients and volunteers but laboratory and animal studies have been excluded as have studies on other porphyrins such as Photofrin, 5-aminolevulinic acid, methyl aminolevulinate and studies reporting other clinical applications for HAL. Topical HAL PDT has potential as a non-surgical tissue-preserving treatment for CIN and persistent oncogenic human papilloma virus infections. HAL PDT selectively treats the entire epithelial sheet, without the tissue destruction seen in excisional procedures. The authors believe that this treatment could replace surgery in a large proportion of patients. It would be of particular value to the high percentage of women who are interested in future child-bearing. If the treatment is approved, it is very likely that physicians will want to use this treatment, as many patients will be keen to consider a non-surgical option.

Detection of cervical intraepithelial neoplasias and cancers in cervical tissue by in vivo light scattering

PubMed Central

Mourant, Judith R.; Bocklage, Thérese J.; Powers, Tamara M.; Greene, Heather M.; Dorin, Maxine H.; Waxman, Alan G.; Zsemlye, Meggan M.; Smith, Harriet O.

2009-01-01

Objective To examine the utility of in vivo elastic light scattering measurements to identify cervical intraepithelial neoplasias (CIN) 2/3 and cancers in women undergoing colposcopy and to determine the effects of patient characteristics such as menstrual status on the elastic light scattering spectroscopic measurements. Materials and Methods A fiber optic probe was used to measure light transport in the cervical epithelium of patients undergoing colposcopy. Spectroscopic results from 151 patients were compared with histopathology of the measured and biopsied sites. A method of classifying the measured sites into two clinically relevant categories was developed and tested using five-fold cross-validation. Results Statistically significant effects by age at diagnosis, menopausal status, timing of the menstrual cycle, and oral contraceptive use were identified, and adjustments based upon these measurements were incorporated in the classification algorithm. A sensitivity of 77±5% and a specificity of 62±2% were obtained for separating CIN 2/3 and cancer from other pathologies and normal tissue. Conclusions The effects of both menstrual status and age should be taken into account in the algorithm for classifying tissue sites based on elastic light scattering spectroscopy. When this is done, elastic light scattering spectroscopy shows good potential for real-time diagnosis of cervical tissue at colposcopy. Guiding biopsy location is one potential near-term clinical application area, while facilitating ”see and treat” protocols is a longer term goal. Improvements in accuracy are essential. PMID:20694193

Risk factors for persistent cervical intraepithelial neoplasia grades 1 and 2: managed by watchful waiting.

PubMed

Ho, Gloria Y F; Einstein, Mark H; Romney, Seymour L; Kadish, Anna S; Abadi, Maria; Mikhail, Magdy; Basu, Jayasri; Thysen, Benjamin; Reimers, Laura; Palan, Prabhudas R; Trim, Shelly; Soroudi, Nafisseh; Burk, Robert D

2011-10-01

: This study examines risk factors for persistent cervical intraepithelial neoplasia (CIN) and examines whether human papillomavirus (HPV) testing predicts persistent lesions. : Women with histologically diagnosed CIN 1 or CIN 2 (n = 206) were followed up every 3 months without treatment. Human papillomavirus genotyping, plasma levels of ascorbic acid, and red blood cell folate levels were obtained. Cervical biopsy at 12 months determined the presence of CIN. Relative risk (RR) was estimated by log-linked binomial regression models. : At 12 months, 70% of CIN 1 versus 54% of CIN 2 lesions spontaneously regressed (p < .001). Levels of folate or ascorbic acid were not associated with persistent CIN at 12 months. Compared with HPV-negative women, those with multiple HPV types (RRs ranged from 1.68 to 2.17 at each follow-up visit) or high-risk types (RRs range = 1.74-2.09) were at increased risk for persistent CIN; women with HPV-16/18 had the highest risk (RRs range = 1.91-2.21). Persistent infection with a high-risk type was also associated with persistent CIN (RRs range = 1.50-2.35). Typing for high-risk HPVs at 6 months only had a sensitivity of 46% in predicting persistence of any lesions at 12 months. : Spontaneous regression of CIN 1 and 2 occurs frequently within 12 months. Human papillomavirus infection is the major risk factor for persistent CIN. However, HPV testing cannot reliably predict persistence of any lesion.

Depth of Cervical Intraepithelial Neoplasia Grade 3 in Peruvian Women: Implications for Therapeutic Depth of Necrosis.

PubMed

Taxa, Luis; Jeronimo, Jose; Alonzo, Todd A; Gage, Julia; Castle, Philip E; Cremer, Miriam L; Felix, Juan C

2018-01-01

To determine the involvement of cervical intraepithelial neoplasia grade 3 (CIN3) in a population of women in a lower-resource setting. One hundred twelve consecutive cone excision specimens with histological diagnosis of CIN3 were retrieved from the National Institute of Neoplastic Diseases in Lima Peru. Two pathologists independently evaluated each specimen microscopically and confirmed 107 cases that could be measured by optical micrometry. Depth and breadth of the lesions were measured microscopically. The mean maximal depth of cervical involvement by CIN3 was 2 ± 0.13 mm; depth was less than 3.5 mm in 89.7% of cases and less than 5 mm in 93.5%. Mean breadth of CIN3 was 7.3 ± 4.4 mm; breadth was less than 15.9 mm in 95% of cases and less than 20.5 mm in 99.7%. The correlation coefficient between breadth and depth of CIN3 was 0.61. No significant correlation was found between age and depth. Depth of CIN3 involvement in a developing country is significantly deeper than that reported in the United States. Treatment selection for women with CIN3 and risk of treatment failure may vary between developing and developed countries because of the difference in the depth of lesions. Countries with underscreened populations need to consider the increased disease severity in devising treatment strategies.

Anal and Cervical High-Risk Human Papillomavirus Genotyping in Women With and Without Genital Neoplasia.

PubMed

Bregar, Amy J; Cronin, Beth; Luis, Christine; DiSilvestro, Paul; Schechter, Steven; Pisharodi, Latha; Raker, Christina; Clark, Melissa; Robison, Katina

2018-04-01

The aim of the study was to compare the prevalence, genotypes, and rates of concomitant anal and cervical high-risk human papillomavirus (HR-HPV) in women with and without a history of HPV-related genital neoplasia. This was a prospective cohort study conducted from December 2012 to February 2014. Women with a history of neoplasia were considered the high-risk group. Women without a history of neoplasia were considered the low-risk group. Cervical and anal cytology and HPV genotyping were performed. All women with abnormal anal cytology were referred for anoscopy. One hundred eighty-four women met inclusion criteria. High-risk HPV was detected in the anal canal of 17.4% of the high-risk group and 1.5% of the low-risk group (p = .003). High-risk HPV was detected in the cervix of 30.5% of the high-risk group and 7.6% of the low-risk group (p < .001). Concomitant anal and cervical high-risk HPV was detected in 4.4% of the high-risk group and was not detected in the low-risk group (p = .2). Among women with anal intraepithelial neoplasia 2 or greater (n = 5), 60% had HR-HPV detected in the anal canal while none had HR-HPV detected in the cervix. Women with a history of genital neoplasia are more likely to be positive for anal and cervical HR-HPV compared with women without a history of genital neoplasia. Although there was no significant difference in rates of concomitant HR-HPV between low- and high-risk groups, HR-HPV can be found concomitantly in the anus and the cervix and may be associated with anal intraepithelial neoplasia or carcinoma.

Does the vaginal microbiota play a role in the development of cervical cancer?

PubMed Central

Kyrgiou, Maria; Mitra, Anita; Moscicki, Anna-Barbara

2016-01-01

Persistent infection with oncogenic Human Papillomavirus (HPV) is necessary but not sufficient for the development of cervical cancer. The factors promoting persistence as well those triggering carcinogenetic pathways are incompletely understood. Rapidly evolving evidence indicates that the vaginal microbiome (VM) may play a functional role (both protective and harmful) in the acquisition and persistence of HPV, and subsequent development of cervical cancer. The first studies examining the vaginal microbiome and the presence of an HPV infection using next generation sequencing techniques (NGS) identified higher microbial diversity in HPV-positive as opposed to HPV-negative women. Furthermore, there appears to be a temporal relationship between the VM and HPV infection in that specific community state types (CSTs) may be correlated with a higher chance of progression or regression of the infection. Studies describing the VM in women with pre-invasive disease (squamous intra-epithelial neoplasia – SIL) consistently demonstrate a dysbiosis in women with the more severe disease. Although it is plausible that the composition of the VM may influence the host innate immune response, susceptibility to infection and the development of cervical disease, the studies to date do not prove causality. Future studies should explore the causal link between the VM and the clinical outcome in longitudinal samples from existing biobanks. PMID:27477083

High grade anal intraepithelial neoplasia among HIV-1-infected men screening for a multi-center clinical trial of a human papillomavirus vaccine

PubMed Central

Wilkin, Timothy; Lee, Jeannette Y.; Lensing, Shelly Y.; Stier, Elizabeth A.; Goldstone, Stephen E.; Berry, J. Michael; Jay, Naomi; Aboulafia, David M.; Einstein, Mark H.; Saah, Alfred; Mitsuyasu, Ronald T.; Palefsky, Joel M.

2013-01-01

Purpose High-grade anal intraepithelial neoplasia (HGAIN) is the precursor lesion to invasive anal cancer. HPV vaccination holds great promise for preventing anal cancer. Methods We examined 235 HIV-1-infected men screening for participation in a multi-site clinical trial of a quadrivalent HPV vaccine. All participants had anal swabs obtained for HPV testing and cytology, and high resolution anoscopy with biopsies of visible lesions to assess for HGAIN. Results HPV 16 and 18 were detected in 23% and 10%, respectively; abnormal anal cytology was found in 56% and HGAIN in 30%. HGAIN prevalence was significantly higher in those with HPV 16 detection compared to those without (38% vs. 17%, P=.01). Use of antiretroviral therapy, nadir and current CD4+ cell count were not associated with abnormal anal cytology or HGAIN. Conclusion HGAIN is highly prevalent in HIV-infected men. Further studies are needed on treatment and prevention of HGAIN. PMID:23611828

Prevalence of abnormal anal cytology and high-grade squamous intraepithelial lesions among a cohort of HIV-infected men who have sex with men.

PubMed

Sendagorta, Elena; Herranz, Pedro; Guadalajara, Hector; Bernardino, Jose Ignacio; Viguer, Jose María; Beato, María José; García-Olmo, Damian; Peña, Jose María

2014-04-01

The incidence of anal cancer among HIV-infected patients is higher than that in other populations. Anal high-grade squamous intraepithelial lesions are considered precursors to invasive squamous-cell carcinomas and are strongly associated to high-risk human papillomavirus infection. The aim of this study is to determine the prevalence of anal high-grade squamous intraepithelial lesions through screening based on cytology and high-resolution anoscopy with biopsy in a cohort of HIV-infected men who have sex with men. This investigation is an observational cross-sectional cohort study. The study was conducted in the HIV unit of a tertiary hospital in Spain. Three hundred HIV-infected men who have sex with men participated. Physical examination led to a diagnosis of perianal squamous-cell carcinoma and high-grade squamous intraepithelial lesions in 2 patients who were then excluded. Anal liquid cytology was performed. Patients with cytological abnormalities underwent high-resolution anoscopy and biopsy. The primary outcome measured was biopsy-proven high-grade squamous intraepithelial lesions. The median age was 41 ± 10.5 years. The mean and nadir CD4 cell counts were 651 ± 205 cells/mm(3) (interquartile range, 438-800) and 273 ± 205 cells/mm(3) (interquartile range, 131-362). High-risk human papillomavirus was detected in 80.9% of patients, and human papillomavirus 16 was detected in 35.9% of patients. The mean number of human papillomavirus genotypes was 4.6 ± 2.9 (CI, 2-6). Anal cytology was abnormal in 40.9% of patients (n = 122/298; interquartile range, 35.4%-46.6%). High-resolution anoscopy and biopsies were performed in 119 patients. The results of histological analyses were as follows: normal, 7.7% (n = 23); condyloma, 4.3% (n = 13); anal intraepithelial neoplasia 1, 5.7% (n = 17); anal intraepithelial neoplasia 2, 14% (n = 42); and anal intraepithelial neoplasia 3, 8% (n = 24). The overall prevalence of high-grade squamous intraepithelial lesions among

Pregnancy incidence and outcome before and after cervical intraepithelial neoplasia: a retrospective cohort study

PubMed Central

Kalliala, Ilkka; Anttila, Ahti; Nieminen, Pekka; Halttunen, Mervi; Dyba, Tadeusz

2014-01-01

We performed a retrospective cohort study of 3530 women treated for cervical intraepithelial neoplasia (CIN) in Helsinki University Central Hospital, Finland, to investigate whether CIN treatment itself affects pregnancy incidence and outcome. We estimated the incidence of live births, miscarriages, extrauterine pregnancies, molar pregnancies, and termination of pregnancies (TOPs) before and after CIN treatment using nationwide registers. Women were followed up until death, emigration, sterilization, or the end of 2004. The comparison of incidence of pregnancy outcomes before and after the treatment was estimated by calculating hazard ratios (HRs) with conditional Poisson regression. After 76,162 woman-years of follow-up, the incidence of any pregnancy remained constant over CIN-treatment, HR 1.02 and 95% confidence interval (CI) 0.97–1.08, but the incidence of the first pregnancy was significantly elevated after treatment, HR 1.13, and 95% CI 1.03–1.23. The incidence of live births was significantly elevated after treatment, HR 1.08 and 95% CI 1.01–1.15. Incidence of miscarriages, TOPs, extrauterine pregnancies, and molar pregnancies was not elevated. TOPs was significantly increased in the first pregnancy, HR 1.40, 95% CI 1.15–1.72 and after treatment by the loop electrosurgical excision procedure (LEEP), HR 1.36, 95% CI 1.15–1.60. CIN treatment did not reduce pregnancy incidence and women had more live births after than before CIN treatment. TOPs was more common in the first pregnancy or after treatment by LEEP. We encourage research on the psychosocial consequences of CIN treatment also in other countries and settings. PMID:25146172

[Screening of anal intraepithelial neoplasia in risk groups: descriptive study of sexual habits and other sexual transmitted infections].

PubMed

Padilla-España, Laura; Repiso-Jiménez, Juan Bosco; Frieyro-Elicegui, Marta; Rivas-Ruiz, Francisco; Robles, Luis; de Troya, Magdalena

2014-02-20

Anal intraepithelial neoplasia is considered a precursor lesion of anal squamous carcinoma. The population with increased risk of this conditions are immunocompromised individuals, especially HIV-infected, with anal sex practices. The aim of this study was to describe the sexual habits of patients who were seen in sexually transmitted infections (STIs) consult in our service in whom anal cytology was performed as well as the association of anal dysplasia to other STIs. We performed a retrospective cohort study that included those patients in whom, according to our protocol, anal cytology was performed between 2008 and 2011. Also we conducted a survey on sexual habits and screening for other STIs. Finally, we conducted a descriptive and analytical study assessing bivariate distribution of cytological alterations and grade of anal dysplasia. A total of 347 anal cytologies were performed, and 48.1% were abnormal. Statistically significant differences were found between the presence of condylomata perianal/endoanal, HIV infection, Chlamydia trachomatis infection and the presence of cytologic alterations. There was a high incidence of anal dysplasia in our group of individuals with risky sexual habits; however, it is probably underdiagnosed due to its subclinical nature and lack of a well-established screening protocol. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Recutting prostate needle core biopsies with high grade prostatic intraepithelial neoplasia increases detection of adenocarcinoma.

PubMed

Rapp, David E; Msezane, Lambda P; Reynolds, W Stuart; Lotan, Tamara L; Obara, Piotr; O'Connor, R Corey; Taxy, Jerome B; Gerber, Glenn S; Zagaja, Gregory P

2009-02-01

We sought to evaluate the ability of biopsy core recutting to increase cancer detection in patients with high grade prostatic intraepithelial neoplasia (HGPIN). This prospective study encompasses all patients undergoing 12 core TRUS guided prostate biopsy between February 2004 and January 2007. In patients with HGPIN on initial biopsy, the paraffin blocks were resampled for cancer by additional deeper levels per core. Additional analysis was performed in the patients with HGPIN in order to detect whether significant differences in prebiopsy variables were associated with patients subsequently found to have benign versus carcinoma on recutting. Last, the costs associated with this procedure were studied. Forty of 584 (6.8%) patients undergoing prostate biopsy were found to have HGPIN in the absence of prostatic adenocarcinoma on initial histopathology. Following recutting, 12.5% (5/40) of these patients were found to have prostatic adenocarcinoma not previously detected. Of the remaining 35 patients, 18 underwent repeat biopsy. Of these, five patients were found to have adenocarcinoma and three were found to have persistent HGPIN. The PSA, PSA density (PSAD), and PSA velocity (PSAV) prior to initial biopsy were not statistically different when comparing patients found to have benign tissue versus carcinoma on recutting. In patients with HGPIN, at our institution, recutting the biopsy would yield a cost savings of $436/patient as opposed to universal rebiopsy. Our data suggest that prostate biopsy recutting may increase cancer detection in patients initially found to have HGPIN. Additionally, a significant cost savings is associated with the recutting protocol.

Phase II trial of imiquimod and HPV therapeutic vaccination in patients with vulval intraepithelial neoplasia

PubMed Central

Daayana, S; Elkord, E; Winters, U; Pawlita, M; Roden, R; Stern, P L; Kitchener, H C

2010-01-01

Background: Vulval intraepithelial neoplasia (VIN) is a premalignant condition, which is frequently associated with type HPV16 infection, and multifocal disease has high rates of surgical treatment failure. Methods: We report a phase II clinical trial of the topical immunomodulator, imiquimod, for 8 weeks, followed by 3 doses (weeks 10, 14 and 18) of therapeutic human papillomavirus (HPV) vaccination (TA-CIN, fusion protein HPV16 E6E7L2) in 19 women with VIN grades 2 and 3. Histology and HPV testing of biopsies were performed at weeks 0, 10, 20 and 52. Intralesional infiltration of T-cell subsets and lymphocyte proliferation for HPV systemic immune responses were also assessed. Results: Lesion response (complete regression of VIN on histology) was observed in 32% (6 out of 19) of women at week 10, increasing to 58% (11 out of 19) at week 20 and 63% (12 out of 19) at week 52. At this time, 36% (5 out of 14) of lesions showed HPV16 clearance and 79% (15 out of 19) of women were symptom free. At week 20, after treatment with imiquimod and vaccination, there was significantly increased local infiltration of CD8 and CD4 T cells in lesion responders; in contrast, non-responders (persistent VIN by histology) showed an increased density of T regulatory cells. After vaccination, only lesion responders had significantly increased lympho-proliferation to the HPV vaccine antigens. Conclusion: The therapeutic effect of treatment depends on the differential immune response of responders and non-responders with affect locally and systemically. PMID:20234368

Medical interventions for high-grade vulval intraepithelial neoplasia.

PubMed

Pepas, Litha; Kaushik, Sonali; Nordin, Andy; Bryant, Andrew; Lawrie, Theresa A

2015-08-18

This is an updated version of a review first published in theCochrane Database of Systematic Reviews, Issue 4, in 2011. Vulval intraepithelial neoplasia (VIN) is a pre-cancerous condition of the vulval skin and its incidence is increasing in women under 50 years. High-grade VIN (also called usual-type VIN (uVIN) or VIN 2/3 or high-grade vulval intraepithelial lesion) is associated with human papilloma virus (HPV) infection and may progress to vulval cancer, therefore is usually actively managed. There is no consensus on the optimal management of high-grade VIN; and the high morbidity and relapse rates associated with surgical interventions make less invasive interventions highly desirable. To evaluate the effectiveness and safety of medical (non-surgical) interventions for high-grade VIN. We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 3), MEDLINE and EMBASE (up to 30 March 2015). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Randomised controlled trials (RCTs) that assessed non-surgical interventions in women diagnosed with high-grade VIN. We used Cochrane methodology with two review authors independently abstracting data and assessing risk of bias. Where possible, we synthesised data in meta-analyses using random effects methods. Five trials involving 297 women with high-grade VIN (defined by trial investigators as VIN 2/3 or VIN 3 or 'high-grade' lesions) met our inclusion criteria: three trials assessed the effectiveness of topical imiquimod versus placebo; one assessed topical cidofovir versus topical imiquimod; and one assessed low- versus high-dose indole-3-carbinol in similar types of participants. Three trials were at a moderate to low risk of bias, two were at a potentially high risk of bias.Meta-analysis of the three trials comparing

Clinical effectiveness and cost-effectiveness of quadrivalent human papillomavirus vaccination in HIV-negative men who have sex with men to prevent recurrent high-grade anal intraepithelial neoplasia.

PubMed

Deshmukh, Ashish A; Chiao, Elizabeth Y; Das, Prajnan; Cantor, Scott B

2014-12-05

We examined the long-term clinical and economic benefits of quadrivalent human papillomavirus (qHPV) vaccine as a secondary/adjunct prevention strategy in the prevention of recurrent high-grade intraepithelial neoplasia (HGAIN) in HIV-negative men who have sex with men (MSM) and are 27 years or older. We constructed a Markov model to evaluate the clinical effectiveness and cost-effectiveness of two strategies: (1) no qHPV vaccine after treatment for HGAIN versus (2) qHPV vaccine after treatment for HGAIN. Model parameters, including natural history of anal cancer, vaccine efficacy measured in terms of hazard ratio (HR) (decrease in the risk of recurrent HGAIN), HGAIN treatment efficacy, utilities, and costs, were obtained from the literature. The outcomes were measured in terms of lifetime risk of anal cancer, lifetime cost, quality-adjusted life years, and incremental cost-effectiveness ratios (ICERs). Sensitivity analysis was conducted on all model parameters. We found that vaccinating HIV-negative MSM reduced the lifetime risk of anal cancer by 60.77% at an ICER of US$87,240 per quality-adjusted life-year. The results were highly sensitive to vaccine efficacy, transition of HGAIN to anal cancer, cost of treatment for HGAIN, vaccine degree of protection over time, and the vaccine duration of protection and less sensitive to HPV clearance, cost of qHPV vaccine, and the transitions from normal to low-grade anal intraepithelial neoplasia (LGAIN) and normal to HGAIN. With an HR of 0.3, the ICER was well below a $50,000 willingness-to-pay threshold; with an HR of 0.5, the ICER was still below a threshold of $100,000. The most critical disease-related factor influencing the cost-effectiveness was the progression of HGAIN to anal cancer. At an annual transition probability below 0.001, the ICER was below $50,000. Vaccinating HIV-negative MSM treated for HGAIN decreases the lifetime risk of anal cancer and is likely to be a cost-effective intervention. Published by

The role of human papillomavirus vaccines in cervical neoplasia.

PubMed

Stern, P L; Faulkner, R; Veranes, E C; Davidson, E J

2001-10-01

Cervical cancer is the second most common cause of cancer-related death in women, in some developing countries accounting for the highest cancer mortality. The evidence for the association of high-risk human papillomavirus types with the aetiology of cervical neoplasia is firmly established, human papillomavirus being detected in virtually all cervical cancers. The risk of progression of precursor cervical intra-epithelial neoplasia lesions is associated with persistence of human papillomavirus infection. One strategy for the management of cervical neoplasia worldwide could be the development of prophylactic and/or therapeutic human papillomavirus vaccines. This chapter will discuss the natural history of human papillomavirus infection, viral immunity and the clinical course of resultant disease as the background to the effective design and use of human papillomavirus vaccines for protection or therapy. The progress of ongoing phase I and II clinical trials for several different vaccine preparations and the challenges for establishing their future use will be discussed. Copyright 2001 Harcourt Publishers Ltd.

GATA3 expression in primary vulvar Paget disease: a potential pitfall leading to misdiagnosis of pagetoid urothelial intraepithelial neoplasia.

PubMed

Morbeck, Diogo; Tregnago, Aline C; Baiocchi, Glauco; Sacomani, Carlos; Peresi, Patricia M; Osório, Cynthia T; Schutz, Luciana; Bezerra, Stephania M; de Brot, Louise; Cunha, Isabela W

2017-02-01

GATA3 has been reported as a specific urothelial marker among organs in the pelvic region, and has been classified as highly sensitive and specific for urothelial and breast carcinomas. Our aim was to verify GATA3 expression in extramammary Paget disease, and to determine whether it can be use to differentiate primary vulvar Paget disease from pagetoid urothelial intraepithelial neoplasia (PUIN). We also analysed HER2 protein expression and HER2 gene amplification and their roles as prognostic factors in extramammary Paget disease. We analysed GATA3 and HER2 expression in 11 primary vulvar Paget disease cases and two PUIN cases. All cases showed nuclear expression of GATA3. Of 13 cases, five were equivocal for HER2 expression (score 2+) and one was positive (3+). Fluorescence in-situ hybridization results showed amplification in two of these six cases. Both HER2-amplified cases were invasive. GATA3 was positive in all extramammary Paget disease cases tested (13 cases), and it has no value for differentiating between primary and secondary vulvar Paget disease from the urological tract. HER2 amplification might confer an aggressive and invasive pattern in primary vulvar Paget disease, as both amplified cases showed an invasive pattern. © 2016 John Wiley & Sons Ltd.

The effectiveness of conization treatment for post-menopausal women with high-grade cervical intraepithelial neoplasia

PubMed Central

CHENG, XIAODONG; FENG, YAN; WANG, XINYU; WAN, XIAOYUN; XIE, XING; LU, WEIGUO

2013-01-01

The aim of this study was to evaluate the effectiveness of conization in the diagnosis and treatment of high-grade cervical intraepithelial neoplasia (CIN) in post-menopausal women. A total of 101 post-menopausal patients who were diagnosed with high-grade lesion CIN by biopsy and in whom conization was used as the primary treatment were examined and 202 pre-menopausal patients were studied as the controls. Clinical and pathological data including symptoms, cytological examination and HPV DNA test results before and after conization treatment were analyzed. Both the cytological abnormalities (57.9 vs. 58.5%, P=0.260) and the positive rate of the HPV DNA test (89.5 vs. 86.4%, P=0.812) did not show a significant difference between the post- and pre-menopausal group. The rate of satisfactory colposcopy was significantly lower in post-menopausal patients compared with pre-menosausal patients (23.2 vs. 68.9%, P<0.001). Post-menopausal patients presented a significantly lower diagnostic consistency between colpscopy-directed biopsy and conization (46.4 vs. 68.9%, P=0.004), and a significantly higher positive margin rate of conization (20.8 vs. 10.9%, P=0.020). A total of 10 of the 101 post-menopausal and 2 of the 202 pre-menopausal women were diagnosed with invasive cancer by conization and underwent further treatment. In conclusion, these data suggest that conization, as a conservative primary treatment, is not suitable for post-menopausal women with high-grade lesion CIN due to the lower rate of satisfactory colposcopy, lower consistency of diagnosis between colposcopy-directed biopsy and conization, and a higher positive margin of conization. PMID:23251264

Vaginal Infections of Albanian women Infected with HPV and their impact in intraepithelial cervical lesions evidenced by Pap test

PubMed Central

Kone, Elsa S; Balili, Avenir D; Paparisto, Piro D; Ceka, Xheladin R; Petrela, Elizana D

2017-01-01

Background: Cervical cytology is the best single method for large screening of the population in identifying precancerous lesions of the uterine cervix. Aim: To estimate the frequency of human papillomavirus (HPV) positivity in a group of Albanian women, the prevalence of vaginal coinfections, and the relationship of coinfections with HPV, as well as their role in metaplasia or cervical intraepithelial lesions (CIN). Materials and Methods: In this retrospective study, 2075 vaginal smears were examined. The Papanicolaou stain was used for all slides. The New Bethesda System 2001 was used for the interpretations of the smears. Data analysis was completed using the Statistical Package for the Social Sciences version 19.0. Results: Prevalence of HPV positivity was 43.9% with an average age of 35.48 ± 9.27 years. Candida coinfection resulted in 57.8% of HPV positive women with a significant relationship between them. Gardnerella coinfection resulted in 36 (23%), mixed flora in 34 (8%), and Trichomonas vaginalis in 50% of HPV positive woman. Among the women with positive HPV, 19% had CIN, 8% had metaplasia, and 1% had metaplasia and CIN; 9% of the women with HPV had CIN1 and one of the coinfections. Conclusions: There is a strong relationship between CIN1 and HPV positivity as well as between CIN1 and coinfections. HPV infection is a major factor contributing to metaplasia, and bacterial coinfections in HPV positive women have a statistically significant impact in the development of metaplasia. PMID:28182076

[High-risk human papilloma virus and cervical intraepithelial neoplasia in women at 2 hospitals in Mexico City].

PubMed

Hernández-Hernández, Dulce Ma; García-Carrancá, Alejandro; Guido-Jiménez, Miriam C; González-Sánchez, José Luis; Cruz-Talonia, Fernando; Apresa-García, Teresa; Martínez-Elizondo, Olga A; Ornelas-Bernal, Laura; Alvarado-Cabrera, Isabel; Muñoz, Sergio

2002-01-01

To determine the high risk HPV (HR-HPV) association with Cervical Intraepithelial Neoplasia (CIN) in women of two Dysplasia Clinics in Mexico City. Prolective case-control study was done. Women with and without security affiliation attended in Instituto Mexicano del Seguro Social (Hospital 1) and Hospital General de México (Hospital 2) were included in the study. Cases were women with histopathologic diagnosis of CIN and controls were women with negative dysplasia in cytologic study (Pap). Information was obtained by direct interview. HR-HPV was determined by Hybrid Capture II assay, in cervical samples. Bivariate and logistic regression analysis was done. One hundred and two cases and 192 controls from Hospital 1 and 89 cases and 66 controls from Hospital 2 were included. 83.3% and 77.3% of women from Hospital 1 and 2 respectively were positive to HR-HPV. The association HR-HPV and CIN in Hospital 1 was ORa = 40.6, C.I. 95% = 17-96.8; while in Hospital 2 there was not association. Age was an effect modifier in the HR-HVP and CIN association, in Hospital 1. It was observed a correlation between viral load and CIN degree. The HR-HPV infection frequency in controls and CIN I was higher than the reported in other studies. Age was a modifier in the HR-HPV association and CIN. In dysplasia clinics without medical referral system of patients is possible to observe similar risk factors to cervical cancer.

Prevalence of human papillomavirus types in invasive vulvar cancers and vulvar intraepithelial neoplasia 3 in the United States before vaccine introduction.

PubMed

Gargano, Julia W; Wilkinson, Edward J; Unger, Elizabeth R; Steinau, Martin; Watson, Meg; Huang, Youjie; Copeland, Glenn; Cozen, Wendy; Goodman, Marc T; Hopenhayn, Claudia; Lynch, Charles F; Hernandez, Brenda Y; Peters, Edward S; Saber, Maria Sibug; Lyu, Christopher W; Sands, Lauren A; Saraiya, Mona

2012-10-01

The study aimed to determine the baseline prevalence of human papillomavirus (HPV) types in invasive vulvar cancer (IVC) and vulvar intraepithelial neoplasia 3 (VIN 3) cases using data from 7 US cancer registries. Registries identified eligible cases diagnosed in 1994 to 2005 and requested pathology laboratories to prepare 1 representative block for HPV testing on those selected. Hematoxylin-eosin-stained sections preceding and following those used for extraction were reviewed to confirm representation. Human papillomavirus was detected using L1 consensus polymerase chain reaction (PCR) with PGMY9/11 primers and type-specific hybridization, with retesting of samples with negative and inadequate results with SPF10 primers. For IVC, the confirmatory hematoxylin-eosin slides were re-evaluated to determine histological type. Descriptive analyses were performed to examine distributions of HPV by histology and other factors. Human papillomavirus was detected in 121/176 (68.8%) cases of IVC and 66/68 (97.1%) cases of VIN 3 (p < .0001). Patients with IVC and VIN 3 differed by median age (70 vs 55 y, p = .003). Human papillomavirus 16 was present in 48.6% of IVC cases and 80.9% of VIN 3 cases; other high-risk HPV was present in 19.2% of IVC cases and 13.2% of VIN 3 cases. Prevalence of HPV differed by squamous cell carcinoma histological subtype (p < .0001) as follows: keratinizing, 49.1% (n = 55); nonkeratinizing, 85.7% (n = 14), basaloid, 92.3% (n = 14), warty 78.2% (n = 55), and mixed warty/basaloid, 100% (n = 7). Nearly all cases of VIN 3 and two thirds of IVC cases were positive for high-risk HPV. Prevalence of HPV ranged from 49.1% to 100% across squamous cell carcinoma histological subtypes. Given the high prevalence of HPV in IVC and VIN 3 cases, prophylactic vaccines have the potential to decrease the incidence of vulvar neoplasia.

NOVEL EPIGENETIC CHANGES IN CDKN2A ARE ASSOCIATED WITH PROGRESSION OF CERVICAL INTRAEPITHELIAL NEOPLASIA

PubMed Central

Wijetunga, N. Ari; Belbin, Thomas J.; Burk, Robert D.; Whitney, Kathleen; Abadi, Maria; Greally, John M.; Einstein, Mark H.; Schlecht, Nicolas F.

2016-01-01

Objective To conduct a comprehensive mapping of the genomic DNA methylation in CDKN2A, which codes for the p16INK4A and p14ARF proteins, and 14 of the most promising DNA methylation marker candidates previously reported to be associated with progression of low-grade cervical intraepithelial neoplasia (CIN1) to cervical cancer. Methods We analyzed DNA methylation in 68 HIV-seropositive and negative women with incident CIN1, CIN2, CIN3 and invasive cervical cancer, assaying 120 CpG dinucleotide sites spanning APC, CDH1, CDH13, CDKN2A, CDKN2B, DAPK1, FHIT, GSTP1, HIC1, MGMT, MLH1, RARB, RASSF1, TERT and TIMP3 using the Illumina Infinium array. Validation was performed using high resolution mapping of the target genes with HELP-tagging for 286 CpGs, followed by fine mapping of candidate genes with targeted bisulfite sequencing. We assessed for statistical differences in DNA methylation levels for each CpG loci assayed using univariate and multivariate methods correcting for multiple comparisons. Results In our discovery sample set, we identified dose dependent differences in DNA methylation with grade of disease in CDKN2A, APC, MGMT, MLH1 and HIC1, whereas single CpG locus differences between CIN2/3 and cancer groups were seen for CDH13, DAPK1 and TERT. Only those CpGs in the gene body of CDKN2A showed a monotonic increase in methylation between persistent CIN1, CIN2, CIN3 and cancers. Conclusion Our data suggests a novel link between early cervical disease progression and DNA methylation in a region downstream of the CDKN2A transcription start site that may lead to increased p16INK4A/p14ARF expression prior to development of malignant disease. PMID:27401842

Novel epigenetic changes in CDKN2A are associated with progression of cervical intraepithelial neoplasia.

PubMed

Wijetunga, N Ari; Belbin, Thomas J; Burk, Robert D; Whitney, Kathleen; Abadi, Maria; Greally, John M; Einstein, Mark H; Schlecht, Nicolas F

2016-09-01

To conduct a comprehensive mapping of the genomic DNA methylation in CDKN2A, which codes for the p16(INK4A) and p14(ARF) proteins, and 14 of the most promising DNA methylation marker candidates previously reported to be associated with progression of low-grade cervical intraepithelial neoplasia (CIN1) to cervical cancer. We analyzed DNA methylation in 68 HIV-seropositive and negative women with incident CIN1, CIN2, CIN3 and invasive cervical cancer, assaying 120 CpG dinucleotide sites spanning APC, CDH1, CDH13, CDKN2A, CDKN2B, DAPK1, FHIT, GSTP1, HIC1, MGMT, MLH1, RARB, RASSF1, TERT and TIMP3 using the Illumina Infinium array. Validation was performed using high resolution mapping of the target genes with HELP-tagging for 286 CpGs, followed by fine mapping of candidate genes with targeted bisulfite sequencing. We assessed for statistical differences in DNA methylation levels for each CpG loci assayed using univariate and multivariate methods correcting for multiple comparisons. In our discovery sample set, we identified dose dependent differences in DNA methylation with grade of disease in CDKN2A, APC, MGMT, MLH1 and HIC1, whereas single CpG locus differences between CIN2/3 and cancer groups were seen for CDH13, DAPK1 and TERT. Only those CpGs in the gene body of CDKN2A showed a monotonic increase in methylation between persistent CIN1, CIN2, CIN3 and cancers. Our data suggests a novel link between early cervical disease progression and DNA methylation in a region downstream of the CDKN2A transcription start site that may lead to increased p16(INK4A)/p14(ARF) expression prior to development of malignant disease. Copyright © 2016 Elsevier Inc. All rights reserved.

A randomized study of hexaminolevulinate photodynamic therapy in patients with cervical intraepithelial neoplasia 1/2.

PubMed

Hillemanns, Peter; Garcia, Francisco; Petry, Karl Ulrich; Dvorak, Vladimír; Sadovsky, Oliver; Iversen, Ole-Erik; Einstein, Mark H

2015-04-01

The objective of the study was to investigate the efficacy and safety of hexaminolevulinate (HAL) photodynamic therapy (PDT), a novel therapy for women with cervical intraepithelial neoplasia (CIN)1/2, to define the appropriate population and endpoints for a phase 3 program. This was a double-blind, randomized, placebo-controlled, dose-finding study that included a total of 262 women with biopsy-confirmed CIN 1/2 based on local pathology. Patients received 1 or 2 topical treatments of HAL hydrochloride 0.2%, 1%, 5%, and placebo ointment and were evaluated for response after 3-6 months based on biopsy, Papanicolaou test, and oncogenic human papillomavirus (HPV) test. All efficacy analyses were performed on blinded central histology review to avoid interreader variability. Adverse events, blood biochemistry, and vital signs were assessed after 3 months. There were no statistically significant differences between placebo and either the CIN 1 or combined CIN 1/2 populations. A clear dose effect with a statistically significant response in the HAL 5% group of 95% (18/19 patients) compared to 57% (12/21 patients) in the placebo group (P < .001) was observed at 3 months in women with CIN 2, including an encouraging 83% (5/6 patients) clearance of HPV 16/18 compared to 33% (2/6 patients) in the placebo group at 6 months. The treatment was easy to use and well accepted by patients and gynecologists. Only local self-limiting adverse reactions including discharge, discomfort, and spotting were reported. HAL PDT is a novel therapy that shows promise in the treatment of CIN 2 including clearance of oncogenic HPV, but not of CIN 1. The positive risk/benefit balance makes HAL PDT a tissue-preserving alternative in women of childbearing age who wish to preserve the cervix. Confirmatory studies are planned. Copyright © 2015 Elsevier Inc. All rights reserved.

Helper T lymphocyte response in the peripheral blood of patients with intraepithelial neoplasia submitted to immunotherapy with pegylated interferon-α.

PubMed

Michelin, Márcia Antoniazi; Montes, Letícia; Nomelini, Rosekeila Simões; Trovó, Marco Aurélio; Murta, Eddie Fernando Candido

2015-03-10

Immunotherapy in cancer patients is a very promising treatment and the development of new protocols and the study of the mechanisms of regression is imperative. The objective of this study was to evaluate the production of cytokines in helper T (CD4+) lymphocytes during immunotherapy with pegylated IFN-α in patients with cervical intraepithelial neoplasia (CIN). We conducted a prospective study with 17 patients with CIN II-III using immunotherapy with pegylated IFN-α subcutaneouly weekly, and using flow cytometry we evaluated the peripheric CD4+ T lymphocytes. The results show that in the regression group the patients presented a significant increase in the amount of IFN-γ during the entire immunotherapy, compared with the group without a response. The amount of CD4+ T lymphocytes positive for IL-2, IL-4, IL-10 and TGF-β is significantly lower in patients with good clinical response. The results also demonstrate that patients with regression have a higher amount of intracellular TNF-α in CD4+ T lymphocytes before the start of treatment. Analyzing these data sets, it can be concluded that immunotherapy is a viable clinical treatment for patients with high-grade CIN and that the regression is dependent on the change in the immune response to a Th1 pattern.

Helper T Lymphocyte Response in the Peripheral Blood of Patients with Intraepithelial Neoplasia Submitted to Immunotherapy with Pegylated Interferon-α

PubMed Central

Michelin, Márcia Antoniazi; Montes, Letícia; Nomelini, Rosekeila Simões; Trovó, Marco Aurélio; Murta, Eddie Fernando Candido

2015-01-01

Immunotherapy in cancer patients is a very promising treatment and the development of new protocols and the study of the mechanisms of regression is imperative. The objective of this study was to evaluate the production of cytokines in helper T (CD4+) lymphocytes during immunotherapy with pegylated IFN-α in patients with cervical intraepithelial neoplasia (CIN). We conducted a prospective study with 17 patients with CIN II-III using immunotherapy with pegylated IFN-α subcutaneouly weekly, and using flow cytometry we evaluated the peripheric CD4+ T lymphocytes. The results show that in the regression group the patients presented a significant increase in the amount of IFN-γ during the entire immunotherapy, compared with the group without a response. The amount of CD4+ T lymphocytes positive for IL-2, IL-4, IL-10 and TGF-β is significantly lower in patients with good clinical response. The results also demonstrate that patients with regression have a higher amount of intracellular TNF-α in CD4+ T lymphocytes before the start of treatment. Analyzing these data sets, it can be concluded that immunotherapy is a viable clinical treatment for patients with high-grade CIN and that the regression is dependent on the change in the immune response to a Th1 pattern. PMID:25764160

Quality of life and female sexual function after skinning vulvectomy with split-thickness skin graft in women with vulvar intraepithelial neoplasia or vulvar Paget disease.

PubMed

Lavoué, V; Lemarrec, A; Bertheuil, N; Henno, S; Mesbah, H; Watier, E; Levêque, J; Morcel, K

2013-12-01

Vulvar intraepithelial neoplasia (VIN) and vulvar Paget disease are managed with either vulvectomy, destructive treatments (laser, antimitotic drugs) or immunostimulants. All these options are associated with functional complications. The purpose of this study was to evaluate the surgical technique consisting of skinning vulvectomy with split-thickness skin graft, and its effect on overall quality of life and sexual function. A retrospective study was conducted on thirteen patients who underwent skinning vulvectomy with split-thickness skin graft between 1999 and 2009. Overall quality of life and sexual function were assessed with the Medical Outcome Study Short Form 36 (MOS SF-36) and Female Sexual Function Index (FSFI), respectively. The median age of patients was 54 (range: 33-77) years. Three patients had Paget disease and 10 patients had VIN lesions. The excision margins were clear in 46% of cases. The incidence of occult cancer was 31%. The mean follow-up period was 77 (±35) months. Four patients experienced a relapse of their intraepithelial disease. The mean disease-free survival was 58 (±44) months. There was no significant difference in MOS SF-36 scores between the study population and the general population. The patients assessed with the FSFI regained normal sexual function after the surgical procedure. Skinning vulvectomy with split-thickness skin graft is a feasible technique yielding good results in terms of quality of life and sexual function. It enables occult cancer to be diagnosed in patients with VIN or Paget disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Detection of Actinomyces spp. in cervical exudates from women with cervical intraepithelial neoplasia or cervical cancer.

PubMed

García-García, Alejandra; Coronel-Martínez, Jaime; Leon, David Cantú-de; Romero-Figueroa, María Del Socorro; Caballero-Pantoja, Yolanda Elizabeth; Manzanares-Leal, Gauddy Lizeth; Rodriguez-Morales, Miguel; Sandoval-Trujillo, Horacio; Ramírez-Durán, Ninfa

2017-06-01

Under certain circumstances, Actinomyces behaves as an opportunistic microorganism and can cause actinomycosis, a chronic and inflammatory granulomatous infection. The purpose of this project was to detect the presence of Actinomyces in cervical exudates from women with cervical intraepithelial neoplasia (CIN) and women with cervical cancer. Cervical samples from 92 women were divided into three groups: CIN, cervical cancer and healthy women. Metagenomic DNA extraction was performed following the Qiagen QIAamp Mini Kit protocol. A specific fragment (675 bp) was amplified by PCR in order to detect the presence of Actinomycetales. Samples in which Actinomycetales was detected were subjected to separate amplification reactions with primer pairs for A. israelii, A. viscosus, A. meyeri and A. odontolyticus. Amplified products were observed by 2 % agarose gel electrophoresis. Actinomyces were found in 10 % of women with CIN, 36.6 % of women with cervical cancer and 9 % of healthy women. The species identified in this study were A. meyeri in 14/92 samples (15.2 %), A. viscosus in 10/92 samples (10.8 %), A. odontolyticus in 4/92 samples (4.3 %) and A. israelii in 6/92 samples (6.5 %). Patients with cervical cancer had a higher prevalence of the presence of Actinomyces compared to the CIN and control groups. This is the first study in which a deliberate search of this genus has been performed in women with cervical pathologies. The use of specific primers for each species facilitated their detection in comparison with traditional isolation methods. More information is necessary to understand the molecular mechanisms involved in the complex role that bacterial communities may play in the development of cancer (and vice versa).

Expression of HOXB2, a retinoic acid signaling target in pancreatic cancer and pancreatic intraepithelial neoplasia.

PubMed

Segara, Davendra; Biankin, Andrew V; Kench, James G; Langusch, Catherine C; Dawson, Amanda C; Skalicky, David A; Gotley, David C; Coleman, Maxwell J; Sutherland, Robert L; Henshall, Susan M

2005-05-01

Despite significant progress in understanding the molecular pathology of pancreatic cancer and its precursor lesion: pancreatic intraepithelial neoplasia (PanIN), there remain no molecules with proven clinical utility as prognostic or therapeutic markers. Here, we used oligonucleotide microarrays to interrogate mRNA expression of pancreatic cancer tissue and normal pancreas to identify novel molecular pathways dysregulated in the development and progression of pancreatic cancer. RNA was hybridized to Affymetrix Genechip HG-U133 oligonucleotide microarrays. A relational database integrating data from publicly available resources was created to identify candidate genes potentially relevant to pancreatic cancer. The protein expression of one candidate, homeobox B2 (HOXB2), in PanIN and pancreatic cancer was assessed using immunohistochemistry. We identified aberrant expression of several components of the retinoic acid (RA) signaling pathway (RARalpha, MUC4, Id-1, MMP9, uPAR, HB-EGF, HOXB6, and HOXB2), many of which are known to be aberrantly expressed in pancreatic cancer and PanIN. HOXB2, a downstream target of RA, was up-regulated 6.7-fold in pancreatic cancer compared with normal pancreas. Immunohistochemistry revealed ectopic expression of HOXB2 in 15% of early PanIN lesions and 48 of 128 (38%) pancreatic cancer specimens. Expression of HOXB2 was associated with nonresectable tumors and was an independent predictor of poor survival in resected tumors. We identified aberrant expression of RA signaling components in pancreatic cancer, including HOXB2, which was expressed in a proportion of PanIN lesions. Ectopic expression of HOXB2 was associated with a poor prognosis for all patients with pancreatic cancer and was an independent predictor of survival in patients who underwent resection.

VEGF elicits epithelial-mesenchymal transition (EMT) in prostate intraepithelial neoplasia (PIN)-like cells via an autocrine loop

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gonzalez-Moreno, Oscar; Lecanda, Jon; Green, Jeffrey E.

2010-02-15

Vascular endothelial growth factor (VEGF) is overexpressed during the transition from prostate intraepithelial neoplasia (PIN) to invasive carcinoma. We have mimicked such a process in vitro using the PIN-like C3(1)/Tag-derived Pr-111 cell line, which expresses low levels of VEGF and exhibits very low tumorigenicity in vivo. Elevated expression of VEGF164 in Pr-111 cells led to a significant increase in tumorigenicity, invasiveness, proliferation rates and angiogenesis. Moreover, VEGF164 induced strong changes in cell morphology and cell transcriptome through an autocrine mechanism, with changes in TGF-beta1- and cytoskeleton-related pathways, among others. Further analysis of VEGF-overexpressing Pr-111 cells or following exogenous addition ofmore » recombinant VEGF shows acquisition of epithelial-mesenchymal transition (EMT) features, with an increased expression of mesenchymal markers, such as N-cadherin, Snail1, Snail2 (Slug) and vimentin, and a decrease in E-cadherin. Administration of VEGF led to changes in TGF-beta1 signaling, including reduction of Smad7 (TGF-beta inhibitory Smad), increase in TGF-betaR-II, and translocation of phospho-Smad3 to the nucleus. Our results suggest that increased expression of VEGF in malignant cells during the transition from PIN to invasive carcinoma leads to EMT through an autocrine loop, which would promote tumor cell invasion and motility. Therapeutic blockade of VEGF/TGF-beta1 in PIN lesions might impair not only tumor angiogenesis, but also the early dissemination of malignant cells outside the epithelial layer.« less

Telomere Attrition in Isolated High-Grade Prostatic Intraepithelial Neoplasia and Surrounding Stroma Is Predictive of Prostate Cancer1

PubMed Central

Joshua, Anthony Michael; Vukovic, Bisera; Braudey, Ilan; Hussein, Sundus; Zielenska, Maria; Srigley, John; Evans, Andrew; Squire, Jeremy Andrew

2007-01-01

Abstract The causes of early genomic events underlying the development of prostate cancer (CaP) remain unclear. The onset of chromosomal instability is likely to facilitate the formation of crucial genomic aberrations both in the precursor lesion high-grade prostatic intraepithelial neoplasia (HPIN) and in CaP. Instability generated by telomere attrition is one potential mechanism that could initiate chromosomal rearrangements. In this study, normalized telomere length variation was examined in a cohort of 68 men without CaP who had HPIN only on prostatic biopsies. Multiple significant associations between telomere attrition and eventual diagnosis of CaP in the HPIN and in the surrounding stroma were found. Kaplan-Meier analysis of telomere length demonstrated a significantly increased risk for the development of cancer with short telomeres in the surrounding stroma [P = .035; hazard ratio (HR) = 2.12; 95% confidence interval (95% CI) = 0.231–0.956], and a trend for HPIN itself (P = .126; HR = 1.72; 95% CI = 0.287–1.168). Cox regression analysis also demonstrated significance between the time from the original biopsy to the diagnosis of cancer and telomere length in HPIN and in the surrounding stroma. These analyses showed significance, both alone and in combination with baseline prostate-specific antigen, and lend support to the hypothesis that telomere attrition in prostatic preneoplasia may be fundamental to the generation of chromosomal instability and to the emergence of CaP. PMID:17325746

[Japanese HIV-infected men who have sex with men screened for anal intraepithelial neoplasia].

PubMed

Itoda, Ichiro; Kitamura, Hiroshi

2011-11-01

The prevalence of and the risk factors for abnormal anal cytology among Japanese men who have sex with men (MSM) who have human immunodeficiency virus (HIV) infection have not been fully investigated up to now. We conducted a nested case-control study of 81 HIV-infected Japanese MSM treated with antiretroviral therapy at a sexuality minority affirmative clinic between April 2010 and March 2011. Results showed that 41 (50.6%) of the 81 had normal anal cytology, 13 (16.0%) atypical squamous cells, 24 (29.6%) low-grade squamous intraepithelial lesions, and 3 (3.7%) high-grade squamous intraepithelial lesions. No carcinoma cases were seen. Multivariate analysis showed abnormal anal cytology to be associated with a history of genital condyloma (OR 4.19, p = .021). We concluded that abnormal anal cytology was common among HIV-infected Japanese MSM. Effective screening and management should be planned for precancerous anal lesions.

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion: review of ancillary testing modalities and implications for follow-up.

PubMed

Davey, Diane Davis; Greenspan, David L; Kurtycz, Daniel F I; Husain, Mujtaba; Austin, R Marshall

2010-07-01

To review the cytology category atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), with human papillomavirus (HPV) and other ancillary testing results and according to age group. A literature search was performed on the ASC-H category, and studies analyzing ASC-H according to ancillary testing modalities or patient age groups during the past 4 years were emphasized. The ASC-H category accounts for less than 1% of cytology reports, and 33% to 84% will test positive for oncogenic HPV. The number of patients with cervical intraepithelial neoplasia 2/3 and cancer on biopsy is quite variable, from about 12% to more than 70%, averaging about 40%. The variation reflects patient population as well as local laboratory practices, but older subgroups are more likely to have negative HPV results and negative follow-up. Both the sensitivity of HPV testing for cervical intraepithelial neoplasia 2/3 detection and the negative predictive value for a patient with ASC-H and negative HPV testing average more than 95%. Additional studies evaluating other types of ancillary testing for the ASC-H category are needed. Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion, is an uncommon cytology result, and HPV testing results and biopsy follow-up show variation according to patient age group and local laboratory practices. A negative HPV result in ASC-H offers a high negative predictive value and could be considered as a management strategy in mature women as well as women 30 years and older receiving combined cytology and HPV screening.

Biological similarities and differences between pancreatic intraepithelial neoplasias and intraductal papillary mucinous neoplasms.

PubMed

Moriya, Toshiyuki; Kimura, Wataru; Semba, Shuho; Sakurai, Fumiaki; Hirai, Ichiro; Ma, Jinfeng; Fuse, Akira; Maeda, Kunihiko; Yamakawa, Mitsunori

2005-01-01

Ever since the classification of pancreatic intraepithelial neoplasia (PanIN) was published, studies on the precursor lesions of pancreatic cancer have been advancing along a new directions, using standardized terminology. There are few studies that have examined the biological differences between PanIN and intraductal papillary mucinous neoplasm (IPMN) in detail. PanIN and IPMN, which are similar in morphology, were compared using various indicators, with the aim of identifying the similarities and differences between the two. A total of 46 PanINs and 37 ducts with IPMN were identified in 19 patients with invasive ductal carcinoma and 18 patients with IPMN. These PanINs and IPMNs were examined immunohistologically with respect to the expression patterns of HER2/neu, DPC4/Smad4, Akt/PKB, p53, cyclin A, Ki67, MUC1, and MUC2. Significant differences in the expression of MUC1 and MUC2 were observed between IPMNadenoma and PanIN-2 and between CIS and PanIN-3 (MUC1: p = 0.001 and p = 0.005, respectively; MUC2: p = 0.002 and p < 0.001, respectively). A significant difference in the p53 expression level was also observed between CIS and PanIN-3 (p = 0.015). In both IPMN and PanIN, the grade of atypism increased with increasing expression of HER2/neu, DPC4/Smad4, and Akt/PKB, along with progression in the process of multistage carcinogenesis. Although the expression levels of these factors reflected the grade of atypism, they did not reflect any differences in the grade of biological malignancy between IPMN and PanIN. On the other hand, MUC1 and MUC2 may serve as indicators of the direction of differentiation, i.e., either progression to IDAC or IPMN. Positivity for MUC1 was believed to suggest differentiation into IDAC, and positivity for MUC2 appeared to be indicative of differentiation into IPMN. Such indication of the direction of differentiation seemed to appear in PanIN1-2, even before abnormalities of HER2/neu, Akt/PKB, DPC4/Smad4, p53, and cyclin A expression began

World Health Organization Guidelines for treatment of cervical intraepithelial neoplasia 2-3 and screen-and-treat strategies to prevent cervical cancer.

PubMed

Santesso, Nancy; Mustafa, Reem A; Schünemann, Holger J; Arbyn, Marc; Blumenthal, Paul D; Cain, Joanna; Chirenje, Michael; Denny, Lynette; De Vuyst, Hugo; Eckert, Linda O'Neal; Forhan, Sara E; Franco, Eduardo L; Gage, Julia C; Garcia, Francisco; Herrero, Rolando; Jeronimo, José; Lu, Enriquito R; Luciani, Silvana; Quek, Swee Chong; Sankaranarayanan, Rengaswamy; Tsu, Vivien; Broutet, Nathalie

2016-03-01

It is estimated that 1%-2% of women develop cervical intraepithelial neoplasia grade 2-3 (CIN 2-3) annually worldwide. The prevalence among women living with HIV is higher, at 10%. If left untreated, CIN 2-3 can progress to cervical cancer. WHO has previously published guidelines for strategies to screen and treat precancerous cervical lesions and for treatment of histologically confirmed CIN 2-3. Guidelines were developed using the WHO Handbook for Guideline Development and the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. A multidisciplinary guideline panel was created. Systematic reviews of randomized controlled trials and observational studies were conducted. Evidence tables and Evidence to Recommendations Tables were prepared and presented to the panel. There are nine recommendations for screen-and-treat strategies to prevent cervical cancer, including the HPV test, cytology, and visual inspection with acetic acid. There are seven for treatment of CIN with cryotherapy, loop electrosurgical excision procedure, and cold knife conization. Recommendations have been produced on the basis of the best available evidence. However, high-quality evidence was not available. Such evidence is needed, in particular for screen-and-treat strategies that are relevant to low- and middle-income countries. Copyright © 2015. Published by Elsevier Ireland Ltd.

Accuracy and Cost-Effectiveness of Cervical Cancer Screening by High-Risk HPV DNA Testing of Self-Collected Vaginal Samples

PubMed Central

Balasubramanian, Akhila; Kulasingam, Shalini L.; Baer, Atar; Hughes, James P.; Myers, Evan R.; Mao, Constance; Kiviat, Nancy B.; Koutsky, Laura A.

2010-01-01

Objective Estimate the accuracy and cost-effectiveness of cervical cancer screening strategies based on high-risk HPV DNA testing of self-collected vaginal samples. Materials and Methods A subset of 1,665 women (18-50 years of age) participating in a cervical cancer screening study were screened by liquid-based cytology and by high-risk HPV DNA testing of both self-collected vaginal swab samples and clinician-collected cervical samples. Women with positive/abnormal screening test results and a subset of women with negative screening test results were triaged to colposcopy. Based on individual and combined test results, five screening strategies were defined. Estimates of sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or worse were calculated and a Markov model was used to estimate the incremental cost-effectiveness ratios (ICERs) for each strategy. Results Compared to cytology-based screening, high-risk HPV DNA testing of self-collected vaginal samples was more sensitive (68%, 95%CI=58%-78% versus 85%, 95%CI=76%-94%) but less specific (89%, 95%CI=86%-91% versus 73%, 95%CI=67%-79%). A strategy of high-risk HPV DNA testing of self-collected vaginal samples followed by cytology triage of HPV positive women, was comparably sensitive (75%, 95%CI=64%-86%) and specific (88%, 95%CI=85%-92%) to cytology-based screening. In-home self-collection for high-risk HPV DNA detection followed by in-clinic cytology triage had a slightly lower lifetime cost and a slightly higher quality-adjusted life expectancy than did cytology-based screening (ICER of triennial screening compared to no screening was $9,871/QALY and $12,878/QALY, respectively). Conclusions Triennial screening by high-risk HPV DNA testing of in-home, self-collected vaginal samples followed by in-clinic cytology triage was cost-effective. PMID:20592553

Increased incidence of penile cancer and high-grade penile intraepithelial neoplasia in Denmark 1978-2008: a nationwide population-based study.

PubMed

Baldur-Felskov, Birgitte; Hannibal, Charlotte Gerd; Munk, Christian; Kjaer, Susanne K

2012-02-01

To assess the trends in incidence of penile cancer during 1978-2008 and high-grade penile intraepithelial neoplasia (PIN2/3) during 1998-2008 in Denmark. Using two nationwide registries, we estimated age- and period-specific incidence rates. Log-linear Poisson regression analysis was used to estimate average annual percentage change (AAPC) and 95% confidence intervals (CI). We identified 1,488 men with penile cancer and 285 men with PIN2/3. The incidence of penile cancer increased from 1.0 to 1.3 per 100,000 men-years in 1978-1979 to 2006-2008; this represented an AAPC of 0.8% (95% CI: 0.17-1.37). Squamous cell carcinoma (SCC) was the most common histological type (91.7%). The median age at diagnosis was 67 years, and the age-specific incidence rate of penile SCC increased with increasing age. The incidence rate of PIN2/3 increased significantly (0.5 to 0.9 per 100,000 men-years) in 1998-1999 to 2006-2008, and this represented an AAPC of 7.1% (95% CI: 3.30-11.05). The incidence of penile cancer increased in 1978-2008 in Denmark, and the same applied to PIN2/3 in 1998-2008. A high prevalence of human papillomavirus (HPV) and a low circumcision rate in Denmark may partly explain our results.

HPV E6/E7 RNA In Situ Hybridization Signal Patterns as Biomarkers of Three-Tier Cervical Intraepithelial Neoplasia Grade

PubMed Central

Evans, Mark F.; Peng, Zhihua; Clark, Kelli M.; Adamson, Christine S.-C.; Ma, Xiao-Jun; Wu, Xingyong; Wang, Hongwei; Luo, Yuling; Cooper, Kumarasen

2014-01-01

Cervical lesion grading is critical for effective patient management. A three-tier classification (cervical intraepithelial neoplasia [CIN] grade 1, 2 or 3) based on H&E slide review is widely used. However, for reasons of considerable inter-observer variation in CIN grade assignment and for want of a biomarker validating a three-fold stratification, CAP-ASCCP LAST consensus guidelines recommend a two-tier system: low- or high-grade squamous intraepithelial lesions (LSIL or HSIL). In this study, high-risk HPV E6/E7 and p16 mRNA expression patterns in eighty-six CIN lesions were investigated by RNAscope chromogenic in situ hybridization (CISH). Specimens were also screened by immunohistochemistry for p16INK4a (clone E6H4), and by tyramide-based CISH for HPV DNA. HPV genotyping was performed by GP5+/6+ PCR combined with cycle-sequencing. Abundant high-risk HPV RNA CISH signals were detected in 26/32 (81.3%) CIN 1, 22/22 (100%) CIN 2 and in 32/32 (100%) CIN 3 lesions. CIN 1 staining patterns were typified (67.7% specimens) by abundant diffusely staining nuclei in the upper epithelial layers; CIN 2 lesions mostly (66.7%) showed a combination of superficial diffuse-stained nuclei and multiple dot-like nuclear and cytoplasmic signals throughout the epithelium; CIN 3 lesions were characterized (87.5%) by multiple dot-like nuclear and cytoplasmic signals throughout the epithelial thickness and absence/scarcity of diffusely staining nuclei (trend across CIN grades: P<0.0001). These data are consistent with productive phase HPV infections exemplifying CIN 1, transformative phase infections CIN 3, whereas CIN 2 shows both productive and transformative phase elements. Three-tier data correlation was not found for the other assays examined. The dual discernment of diffuse and/or dot-like signals together with the assay’s high sensitivity for HPV support the use of HPV E6/E7 RNA CISH as an adjunct test for deciding lesion grade when CIN 2 grading may be beneficial (e.g. among

HPV E6/E7 RNA in situ hybridization signal patterns as biomarkers of three-tier cervical intraepithelial neoplasia grade.

PubMed

Evans, Mark F; Peng, Zhihua; Clark, Kelli M; Adamson, Christine S-C; Ma, Xiao-Jun; Wu, Xingyong; Wang, Hongwei; Luo, Yuling; Cooper, Kumarasen

2014-01-01

Cervical lesion grading is critical for effective patient management. A three-tier classification (cervical intraepithelial neoplasia [CIN] grade 1, 2 or 3) based on H&E slide review is widely used. However, for reasons of considerable inter-observer variation in CIN grade assignment and for want of a biomarker validating a three-fold stratification, CAP-ASCCP LAST consensus guidelines recommend a two-tier system: low- or high-grade squamous intraepithelial lesions (LSIL or HSIL). In this study, high-risk HPV E6/E7 and p16 mRNA expression patterns in eighty-six CIN lesions were investigated by RNAscope chromogenic in situ hybridization (CISH). Specimens were also screened by immunohistochemistry for p16INK4a (clone E6H4), and by tyramide-based CISH for HPV DNA. HPV genotyping was performed by GP5+/6+ PCR combined with cycle-sequencing. Abundant high-risk HPV RNA CISH signals were detected in 26/32 (81.3%) CIN 1, 22/22 (100%) CIN 2 and in 32/32 (100%) CIN 3 lesions. CIN 1 staining patterns were typified (67.7% specimens) by abundant diffusely staining nuclei in the upper epithelial layers; CIN 2 lesions mostly (66.7%) showed a combination of superficial diffuse-stained nuclei and multiple dot-like nuclear and cytoplasmic signals throughout the epithelium; CIN 3 lesions were characterized (87.5%) by multiple dot-like nuclear and cytoplasmic signals throughout the epithelial thickness and absence/scarcity of diffusely staining nuclei (trend across CIN grades: P<0.0001). These data are consistent with productive phase HPV infections exemplifying CIN 1, transformative phase infections CIN 3, whereas CIN 2 shows both productive and transformative phase elements. Three-tier data correlation was not found for the other assays examined. The dual discernment of diffuse and/or dot-like signals together with the assay's high sensitivity for HPV support the use of HPV E6/E7 RNA CISH as an adjunct test for deciding lesion grade when CIN 2 grading may be beneficial (e.g. among

Outcomes after management of young women with cervical intraepithelial neoplasia 2 with a 6-month observation protocol.

PubMed

Bleecker, Elizabeth; Koehler, Elizabeth; Smith, Jennifer; Budwit, Debra; Rahangdale, Lisa

2014-01-01

Recommendations regarding treatment of cervical intraepithelial neoplasia (CIN) 2 in women have evolved over the years: young women with CIN 2 may be offered observation with Pap smears and colposcopy every 6 months instead of immediate excision or ablation of disease. The purpose of this study was to observe patient follow-up during the initiation of this management protocol for young women with CIN 2. This was a retrospective review of clinical outcomes of women younger than 30 years with CIN 2 on index biopsy and planned follow-up at UNC between July 2009 and August 2010. A chart review for clinical variables, follow-up visits, and progression of disease was conducted. Primary analysis determined the rate of follow-up and pathology at 6 months. Secondary analysis investigated risk factors for incomplete follow-up. Seventy women met inclusion criteria; 46 were managed with observation. Twenty-eight (60.8%; 28/46) women completed a follow-up visit. Demographic and clinical variables did not reach statistical significance in predicting the likelihood of completion of a follow-up visit, although there was a trend toward greater follow-up in employed patients (odds ratio = 5.25, 95% confidence interval = 0.84-34.78). Approximately half (52.4%; 11/21) of women with a completed cervical biopsy demonstrated regression of disease during the study period. On the basis of these data, follow-up in this population was unpredictable based on basic demographic or clinical factors that we often use to judge likelihood of compliance with medical recommendations. The percentage of patients with regression at follow-up was as expected from the natural history of CIN 2.

Behavior of the PCA3 gene in the urine of men with high grade prostatic intraepithelial neoplasia.

PubMed

Morote, Juan; Rigau, Marina; Garcia, Marta; Mir, Carmen; Ballesteros, Carlos; Planas, Jacques; Raventós, Carles X; Placer, José; de Torres, Inés M; Reventós, Jaume; Doll, Andreas

2010-12-01

An ideal marker for the early detection of prostate cancer (PCa) should also differentiate between men with isolated high grade prostatic intraepithelial neoplasia (HGPIN) and those with PCa. Prostate Cancer Gene 3 (PCA3) is a highly specific PCa gene and its score, in relation to the PSA gene in post-prostate massage urine (PMU-PCA3), seems to be useful in ruling out PCa, especially after a negative prostate biopsy. Because PCA3 is also expressed in the HGPIN lesion, the aim of this study was to determine the efficacy of PMU-PCA3 scores for ruling out PCa in men with previous HGPIN. The PMU-PCA3 score was assessed by quantitative PCR (multiplex research assay) in 244 men subjected to prostate biopsy: 64 men with an isolated HGPIN (no cancer detected after two or more repeated biopsies), 83 men with PCa and 97 men with benign pathology findings (BP: no PCa, HGPIN or ASAP). The median PMU-PCA3 score was 1.56 in men with BP, 2.01 in men with HGPIN (p = 0.128) and 9.06 in men with PCa (p = 0.008). The AUC in the ROC analysis was 0.705 in the subset of men with BP and PCa, while it decreased to 0.629 when only men with isolated HGPIN and PCa were included in the analysis. Fixing the sensitivity of the PMU-PCA3 score at 90%, its specificity was 79% in men with BP and 69% in men with isolated HGPIN. The efficacy of the PMU-PCA3 score to rule out PCa in men with HGPIN is lower than in men with BP.

Human Papillomavirus DNA Methylation Predicts Response to Treatment Using Cidofovir and Imiquimod in Vulval Intraepithelial Neoplasia 3.

PubMed

Jones, Sadie E F; Hibbitts, Samantha; Hurt, Christopher N; Bryant, Dean; Fiander, Alison N; Powell, Ned; Tristram, Amanda J

2017-09-15

Purpose: Response rates to treatment of vulval intraepithelial neoplasia (VIN) with imiquimod and cidofovir are approximately 57% and 61%, respectively. Treatment is associated with significant side effects and, if ineffective, risk of malignant progression. Treatment response is not predicted by clinical factors. Identification of a biomarker that could predict response is an attractive prospect. This work investigated HPV DNA methylation as a potential predictive biomarker in this setting. Experimental Design: DNA from 167 cases of VIN 3 from the RT3 VIN clinical trial was assessed. HPV-positive cases were identified using Greiner PapilloCheck and HPV 16 type-specific PCR. HPV DNA methylation status was assessed in three viral regions: E2, L1/L2, and the promoter, using pyrosequencing. Results: Methylation of the HPV E2 region was associated with response to treatment. For cidofovir ( n = 30), median E2 methylation was significantly higher in patients who responded ( P ≤ 0.0001); E2 methylation >4% predicted response with 88.2% sensitivity and 84.6% specificity. For imiquimod ( n = 33), median E2 methylation was lower in patients who responded to treatment ( P = 0.03; not significant after Bonferroni correction); E2 methylation <4% predicted response with 70.6% sensitivity and 62.5% specificity. Conclusions: These data indicate that cidofovir and imiquimod may be effective in two biologically defined groups. HPV E2 DNA methylation demonstrated potential as a predictive biomarker for the treatment of VIN with cidofovir and may warrant investigation in a biomarker-guided clinical trial. Clin Cancer Res; 23(18); 5460-8. ©2017 AACR . ©2017 American Association for Cancer Research.

Genital Warts and Vulvar Intraepithelial Neoplasia: Natural History and Effects of Treatment and Human Immunodeficiency Virus Infection

PubMed Central

Massad, L. Stewart; Xie, Xianhong; Darragh, Teresa; Minkoff, Howard; Levine, Alexandra M.; Watts, D. Heather; Wright, Rodney L.; D’Souza, Gypsyamber; Colie, Christine; Strickler, Howard D.

2011-01-01

Objective To describe the natural history of genital warts and vulvar intraepithelial neoplasia (VIN) in women with human immunodeficiency virus (HIV). Methods A cohort of 2,791 HIV infected and 953 uninfected women followed for up to 13 years had genital examinations at 6-month intervals, with biopsy for lesions suspicious for VIN. Results The prevalence of warts was 4.4% (5.3% for HIV seropositive women and 1.9% for seronegative women, P < 0.0001). The cumulative incidence of warts was 33% (95% C.I. 30, 36%) in HIV seropositive and 9% (95% C.I. 6, 12%) in seronegative women (P < 0.0001). In multivariable analysis, lower CD4 lymphocyte count, younger age, and current smoking were strongly associated with risk for incident warts. Among 501 HIV seropositive and 43 seronegative women, warts regressed in 410 (82%) seropositive and 41 (95%) seronegative women (P = 0.02), most in the first year after diagnosis. In multivariable analysis, regression was negatively associated with HIV status and lower CD4 count as well as older age. Incident VIN of any grade occurred more frequently among HIV seropositive than seronegative women: 0.42 (0.33 – 0.53) vs 0.07 (0.02 – 0.18)/100 person-years (P < 0.0001). VIN2+ was found in 58 women (55 with and 3 without HIV, P < 0.001). Two women with HIV developed stage IB squamous cell vulvar cancers. Conclusion While genital warts and VIN are more common among HIV seropositive than seronegative women, wart regression is common even in women with HIV, and cancers are infrequent. PMID:21934446

p16 immunostaining in histological grading of anal squamous intraepithelial lesions: a systematic review and meta-analysis.

PubMed

Albuquerque, Andreia; Rios, Elisabete; Dias, Claudia Camila; Nathan, Mayura

2018-02-13

p16 is the most widely studied biomarker in lower anogenital tract squamous intraepithelial lesions and, currently the only recommended biomarker for histological grade assessment. The aim of this systematic review and meta-analysis was to evaluate p16-positive rates according to anal squamous intraepithelial lesions/anal intraepithelial neoplasia (AIN) grade. Two investigators independently searched four electronic databases: PubMed, Web of Sciences, Scopus, and Embase from inception until August 2017. Studies that evaluated p16 immunostaining in histological samples of anal and/or perianal squamous intraepithelial lesions and defined a p16-positive result as diffuse block staining with nuclear or nuclear plus cytoplasmic staining were included. A meta-analysis was performed using a random effects model. Fifteen studies consisting of 790 samples were included. The proportion of p16 expression increased with the severity of histological grade. p16 positivity was 2% (95% CI: 0.2-5%) in normal histology, 12% (95% CI: 2-27%) in low-grade squamous intraepithelial lesions (LSILs)/AIN1 (excluding condylomas), 7% (95% CI: 2-13%) in all LSIL (AIN1/LSIL/condyloma), 76% (95% CI: 61-88%) in AIN2, and 90% (95% CI: 82-95%) in AIN3. For anal high-grade squamous intraepithelial lesions (HSILs), in studies using a two-tiered nomenclature, p16 positivity was 84% (95% CI: 66-96%) and for all HSIL (AIN2, AIN3, HSIL combined) it was 82% (95% CI: 72-91%). In summary, p16 positivity in anal squamous intraepithelial lesions appears to be in a similar range to the commonly described cervical squamous intraepithelial lesions, however, for anal low-grade lesions positivity seems to be lower.

Virologic versus cytologic triage of women with equivocal Pap smears: a meta-analysis of the accuracy to detect high-grade intraepithelial neoplasia.

PubMed

Arbyn, Marc; Buntinx, Frank; Van Ranst, Marc; Paraskevaidis, Evangelos; Martin-Hirsch, Pierre; Dillner, Joakim

2004-02-18

The appropriate management of women with minor cytologic lesions in their cervix is unclear. We performed a meta-analysis to assess the accuracy of human papillomavirus (HPV) DNA testing as an alternative to repeat cytology in women who had equivocal results on a previous Pap smear. Data were extracted from articles published between 1992 and 2002 that contained results of virologic and cytologic testing followed by colposcopically directed biopsy in women with an index smear showing atypical cells of undetermined significance (ASCUS). Fifteen studies were identified in which HPV triage and the histologic outcome (presence or absence of a cervical intraepithelial neoplasia of grade II or worse [CIN2+]) was documented. Nine, seven, and two studies also documented the accuracy of repeat cytology when the cutoff for abnormal cytology was set at a threshold of ASCUS or worse, low-grade squamous intraepithelial lesion (LSIL) or worse, or high-grade squamous intraepithelial lesion (HSIL) or worse, respectively. Random-effects models were used for pooling of accuracy parameters in case of interstudy heterogeneity. Differences in accuracy were assessed by pooling the ratio of the sensitivity (or specificity) of HPV testing to that of repeat cytology. The sensitivity and specificity were 84.4% (95% confidence interval [CI] = 77.6% to 91.1%) and 72.9% (95% CI = 62.5% to 83.3%), respectively, for HPV testing overall and 94.8% (95% CI = 92.7% to 96.9%) and 67.3% (95% CI = 58.2% to 76.4%), respectively, for HPV testing in the eight studies that used the Hybrid Capture II assay. Sensitivity and specificity of repeat cytology at a threshold for abnormal cytology of ASCUS or worse was 81.8% (95% CI = 73.5% to 84.3%) and 57.6% (95% CI = 49.5% to 65.7%), respectively. Repeat cytology that used higher cytologic thresholds yielded substantially lower sensitivity but higher specificity than triage with the Hybrid Capture II assay. The ratio of the sensitivity of the Hybrid Capture II

Germ cell neoplasia in situ (GCNIS): evolution of the current nomenclature for testicular pre-invasive germ cell malignancy.

PubMed

Berney, Daniel M; Looijenga, Leendert H J; Idrees, Muhammad; Oosterhuis, J Wolter; Rajpert-De Meyts, Ewa; Ulbright, Thomas M; Skakkebaek, Niels E

2016-07-01

The pre-invasive lesion associated with post-pubertal malignant germ cell tumours of the testis was first recognized in the early 1970s and confirmed by a number of observational and follow-up studies. Until this year, this scientific story has been confused by resistance to the entity and disagreement on its name. Initially termed 'carcinoma in situ' (CIS), it has also been known as 'intratubular germ cell neoplasia, unclassified' (IGCNU) and 'testicular intraepithelial neoplasia' (TIN). In this paper, we review the history of discovery and controversy concerning these names and introduce the reasoning for uniting behind a new name, endorsed unanimously at the World Health Organization (WHO) consensus classification 2016: germ cell neoplasia in situ (GCNIS). © 2016 John Wiley & Sons Ltd.

The 3-dimensional structure of isolated and small foci of prostatic adenocarcinoma: the morphologic relationship between prostatic adenocarcinoma and prostatic intraepithelial neoplasia.

PubMed

Mai, Kien T; Burns, Bruce F; Stinson, William A; Morash, Christopher

2007-03-01

Transitional histopathologic changes from high-grade prostatic intraepithelial neoplasia (HGPIN) into early prostatic adenocarcinoma (PAC) have not been well studied to date. To investigate the histogenesis of PAC, we examined isolated and small foci of PAC (ISPAC) found in prostatectomy specimens and the 3-dimensional structure of these foci. Twelve consecutive radical prostatectomy specimens having ISPAC, performed for peripheral zone PAC (10 cases) and for transitional zone PAC (2 cases), of Gleason score were studied. One to 2 tissue blocks with representative sections were used. Eight ISPAC, with Gleason score 3 + 3 had complete serial sections of the entire lesion. PAC consisted of continuous, tortuous and branching tubules and acini arising from benign ducts displaying: (a) HGPIN in 5 ISPAC and (b) no HGPIN in 3 ISAPC. At the junctions between benign epithelia with or without HGPIN and malignant epithelia, there were transitional lesions with HGPIN involving small ducts and acini. PAC develops as a result of multiple outpouchings of the epithelium with formation of small ducts and acini showing cytologic atypia and gradual or abrupt loss of basal cells. Grade 3 ISPAC consists of a system of continuous duct pushing into the stroma. There is also evidence suggestive of HGPIN as being both a precursor lesion and an accompanying lesion of PAC.

An approach to the diagnosis of flat intraepithelial lesions of the urinary bladder using the World Health Organization/ International Society of Urological Pathology consensus classification system.

PubMed

Amin, Mahul B; McKenney, Jesse K

2002-07-01

The classification of flat urothelial (transitional cell) lesions with atypia has historically varied in its application from institution to institution with no fewer than six major nomenclature systems proposed in the past 25 years. In 1998, the World Health Organization/ International Society of Urological Pathology (WHO/ISUP) published a consensus classification that included the following categories for flat urinary bladder lesions: reactive atypia, atypia of unknown significance, dysplasia (low-grade intraepithelial neoplasia), and carcinoma in situ (high-grade intraepithelial neoplasia). This classification expands the definition traditionally used for urothelial carcinoma in situ, basing its diagnosis primarily on the severity of cytologic changes. In proposing the classification system for flat lesions of the bladder with atypia, it was hoped that consistent use of uniform diagnostic terminology would ultimately aid in a better understanding of the biology of these lesions. In this review, the authors discuss the history of the concept of flat urothelial neoplasia, the rationale and histologic criteria for the WHO/ISUP diagnostic categories, an approach to the diagnosis of flat lesions, and problems and pitfalls associated with their recognition in routine surgical pathology specimens.

An automated machine vision system for the histological grading of cervical intraepithelial neoplasia (CIN).

PubMed

Keenan, S J; Diamond, J; McCluggage, W G; Bharucha, H; Thompson, D; Bartels, P H; Hamilton, P W

2000-11-01

The histological grading of cervical intraepithelial neoplasia (CIN) remains subjective, resulting in inter- and intra-observer variation and poor reproducibility in the grading of cervical lesions. This study has attempted to develop an objective grading system using automated machine vision. The architectural features of cervical squamous epithelium are quantitatively analysed using a combination of computerized digital image processing and Delaunay triangulation analysis; 230 images digitally captured from cases previously classified by a gynaecological pathologist included normal cervical squamous epithelium (n=30), koilocytosis (n=46), CIN 1 (n=52), CIN 2 (n=56), and CIN 3 (n=46). Intra- and inter-observer variation had kappa values of 0.502 and 0.415, respectively. A machine vision system was developed in KS400 macro programming language to segment and mark the centres of all nuclei within the epithelium. By object-oriented analysis of image components, the positional information of nuclei was used to construct a Delaunay triangulation mesh. Each mesh was analysed to compute triangle dimensions including the mean triangle area, the mean triangle edge length, and the number of triangles per unit area, giving an individual quantitative profile of measurements for each case. Discriminant analysis of the geometric data revealed the significant discriminatory variables from which a classification score was derived. The scoring system distinguished between normal and CIN 3 in 98.7% of cases and between koilocytosis and CIN 1 in 76.5% of cases, but only 62.3% of the CIN cases were classified into the correct group, with the CIN 2 group showing the highest rate of misclassification. Graphical plots of triangulation data demonstrated the continuum of morphological change from normal squamous epithelium to the highest grade of CIN, with overlapping of the groups originally defined by the pathologists. This study shows that automated location of nuclei in cervical

Systematic reviews and meta-analyses of benefits and harms of cryotherapy, LEEP, and cold knife conization to treat cervical intraepithelial neoplasia.

PubMed

Santesso, Nancy; Mustafa, Reem A; Wiercioch, Wojtek; Kehar, Rohan; Gandhi, Shreyas; Chen, Yaolong; Cheung, Adrienne; Hopkins, Jessica; Khatib, Rasha; Ma, Bin; Mustafa, Ahmad A; Lloyd, Nancy; Wu, Darong; Broutet, Nathalie; Schünemann, Holger J

2016-03-01

Cervical intraepithelial neoplasia (CIN) stage 2-3 is a premalignant lesion that can progress to cervical cancer in 10-20 years if untreated. To conduct systematic reviews of randomized and nonrandomized studies for effects of cryotherapy, loop electrosurgical excision procedure (LEEP), and cold knife conization (CKC) as treatment for CIN 2-3. Medline, Embase, and other databases were searched to February 2012 for benefits, and to July 2012 for harms. Additionally, experts were contacted. Keywords for CIN, cervical cancer, and the treatments were used. Studies of nonpregnant women 18 years or older not previously treated for CIN were included. Two investigators independently screened and collected data. Relative risks and proportions were calculated and evidence assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Recurrence rate was 5.3% 12 months after cryotherapy or LEEP, and 1.4% after CKC. There seemed to be little or no differences in frequency of complications after LEEP or cryotherapy, but they occurred more often after CKC. Evidence suggests premature delivery is most common with CKC, but it also occurs after LEEP and cryotherapy. Despite a comprehensive search, there is very low quality evidence and often no evidence for important outcomes, including reproductive outcomes and complications. Studies assessing these outcomes are needed. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Detection of cervical intraepithelial neoplasia by using optical coherence tomography in combination with microscopy

NASA Astrophysics Data System (ADS)

Gallwas, Julia; Jalilova, Aydan; Ladurner, Roland; Kolben, Theresa Maria; Kolben, Thomas; Ditsch, Nina; Homann, Christian; Lankenau, Eva; Dannecker, Christian

2017-01-01

Optical coherence tomography (OCT) is a noninvasive high-resolution imaging technique that permits the detection of cancerous and precancerous lesions of the uterine cervix. The purpose of this study was to evaluate a new system that integrates an OCT device into a microscope. OCT images were taken from loop electrosurgical excision procedure (LEEP) specimens under microscopic guidance. The images were blinded with respect to their origin within the microscopic image and analyzed independently by two investigators using initially defined criteria and later compared to the corresponding histology. Sensitivity and specificity were calculated with respect to the correct identification of high-grade squamous intraepithelial lesions (HSIL). The interinvestigator agreement was assessed by using Cohen's kappa statistics. About 160 OCT images were obtained from 20 LEEP specimens. Sixty randomly chosen images were used to define reproducible criteria for evaluation. The assessment of the remaining 100 images showed a sensitivity of 88% (second investigator 84%) and a specificity of 69% (65%) in detecting HSIL. Surgical microscopy-guided OCT appears to be a promising technique for immediate assessment of microanatomical changes. In the gynecological setting, the combination of OCT with a colposcope may improve the detection of high-grade squamous intraepithelial lesions.

In vitro inhibition of human papillomavirus following use of a carrageenan-containing vaginal gel.

PubMed

Novetsky, Akiva P; Keller, Marla J; Gradissimo, Ana; Chen, Zigui; Morgan, Stephanie L; Xue, Xiaonan; Strickler, Howard D; Fernández-Romero, José A; Burk, Robert; Einstein, Mark H

2016-11-01

To assess in vitro efficacy of Divine 9, a carrageenan-based vaginal lubricant that is being studied as a microbicide to inhibit HPV16 pseudovirus (PsV) infection. Sexually active US women between 19 and 35years without prior HPV vaccination or cervical intraepithelial neoplasia were instructed to use Divine 9 vaginally with an applicator either before sex only or before and after intercourse. Women who applied a single dose of gel returned for cervicovaginal lavage (CVL) collection 1, 4 or 8-12h after intercourse versus those who applied gel before and after intercourse returned 1, 4 or 8-12h after the second gel dose. Carrageenan concentrations were assessed using an ELISA assay and the inhibitory activity was assessed using a PsV-based neutralization assay against HPV16 infection. Carrageenan concentrations and the percentage of PsV16 inhibition were compared using the Wilcoxon rank sum test. Thirteen women were enrolled and thirty specimens from different time-points were assessed. 87% of CVL samples had detectable carrageenans with levels decreasing over time from intercourse. 93% of CVL samples had detectable PsV16 inhibition with median inhibition of 97.5%. PsV16 inhibition decreased over time, but remained high, with median inhibition of 98.1%, 97.4% and 83.4% at 1, 4 and 8-12h, respectively. Higher carrageenan concentrations were associated with higher levels of PsV16 inhibition (rho=0.69). This is the first report of a human study investigating in vitro HPV inhibition of a carrageenan-based vaginal lubricant with CVL collected after sexual intercourse. We demonstrate excellent efficacy in preventing PsV16 infection. Copyright © 2016 Elsevier Inc. All rights reserved.

In Vitro Inhibition of Human Papillomavirus Following Use of a Carrageenan-Containing Vaginal Gel

PubMed Central

Novetsky, Akiva P.; Keller, Marla J.; Gradissimo, Ana; Chen, Zigui; Morgan, Stephanie L.; Xue, Xiaonan; Strickler, Howard D.; Fernández-Romero, José A.; Burk, Robert; Einstein, Mark H.

2016-01-01

Objective To assess in vitro efficacy of Divine 9, a carrageenan-based vaginal lubricant that is being studied as a microbicide to inhibit HPV16 pseudovirus (PsV) infection. Methods Sexually active US women between 19–35 years without prior HPV vaccination or cervical intraepithelial neoplasia were instructed to use Divine 9 vaginally with an applicator either before sex only or before and after intercourse. Women who applied a single dose of gel returned for cervicovaginal lavage (CVL) collection 1, 4 or 8–12 hours after intercourse versus those who applied gel before and after intercourse returned 1, 4 or 8–12 hours after the second gel dose. Carrageenan concentrations were assessed using an ELISA assay and the inhibitory activity was assessed using a PsV-based neutralization assay against HPV16 infection. Carrageenan concentrations and the percentage of PsV16 inhibition were compared using the Wilcoxon rank sum test. Results Thirteen women were enrolled and thirty specimens from different time-points were assessed. 87% of CVL samples had detectable carrageenans with levels decreasing over time from intercourse. 93% of CVL samples had detectable PsV16 inhibition with median inhibition of 97.5%. PsV16 inhibition decreased over time, but remained high, with median inhibition of 98.1%, 97.4% and 83.4% at 1, 4 and 8–12 hours, respectively. Higher carrageenan concentrations were associated with higher levels of PsV16 inhibition (rho=0.69). Conclusions This is the first report of a human study investigating in vitro HPV inhibition of a carrageenan-based vaginal lubricant with CVL collected after sexual intercourse. We demonstrate excellent efficacy in preventing PsV16 infection. PMID:27625046

[Effectiveness of human papillomavirus genotyping for detection of high-grade anal intraepithelial neoplasia compared to anal cytology].

PubMed

Padilla-España, Laura; Repiso-Jiménez, Juan Bosco; Fernández-Sánchez, Fernando; Pereda, Teresa; Rivas-Ruiz, Francisco; Fernández-Morano, Teresa; de la Torre-Lima, Javier; Palma, Fermín; Redondo, Maximino; de Troya-Martín, Magdalena

2016-01-01

The incidence of high-grade anal intraepithelial neoplasia (HGAIN) -with an aetiological based on high-risk types of human papillomavirus- is increasing in some high-risk groups. Screening for HGAIN includes routine anal cytology and, more recently, HPV genotyping. The main objective of this study was to determine the sensitivity and specificity of anal cytology and HPV genotyping for the detection of HGAIN. This is a study to determine the correlation of cytological and microbiological findings with anal biopsy findings in a cohort of patients at high risk of developing AIN referred to the department of sexually transmitted infections of the Hospital Costa del Sol, Spain, between January 2008 and December 2014. Of the 151 patients subjected to screening, a total of 92 patients, all of them with the result of three screening test (anal cytology, genotyping and biopsy) were included in the study. Just under two-thirds (62%) of them were HIV-positive. The sensitivity and specificity of anal cytology to detect HGAIN were 52.8 and 85.7%, respectively (k: 0.328), and 78 and 62.8% to detect two or more HPV oncogenic genotypes (k: 0.417). The detection of oncogenic HPV genotypes allowed the identification of 23 new cases of HGAIN that had been underdiagnosed with anal cytology, with 14 cases containing at least three high-risk genotypes. Anal cytology did not show enough sensitivity in HGAIN screening. HPV genotyping has shown to be a useful tool to detect HGAIN cases, although it could lead to an over-diagnosis as a solitary screening procedure. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

The impact of bivalent HPV vaccine on cervical intraepithelial neoplasia by deprivation in Scotland: reducing the gap.

PubMed

Cameron, Ross L; Kavanagh, Kimberley; Cameron Watt, D; Robertson, Chris; Cuschieri, Kate; Ahmed, Syed; Pollock, Kevin G

2017-10-01

Cervical cancer disproportionately affects women from lower socioeconomic backgrounds. A human papillomavirus (HPV) vaccination programme was introduced in Scotland in 2008 with uptake being lower and inequitable in a catch-up cohort run for the first three years of the programme compared with the routine programme. The socioeconomic differences in vaccine uptake have the potential to further increase the inequality gap in regards to cervical disease. Vaccination status was linked to demographic, cytological and colposcopic data, which are routinely collected by the Scottish HPV surveillance system. Incidence rates and relative risk of cervical intraepithelial neoplasia (CIN) 1, 2 and 3 in unvaccinated and vaccinated women were stratified by birth year and deprivation status using Poisson regression. Women who received three doses of HPV vaccine have significantly decreased risk of CIN 1, 2 and 3. Vaccine effectiveness was greater in those women from the most deprived backgrounds against CIN 2 and 3 lesions. Compared with the most deprived, unvaccinated women, the relative risk of CIN 3 in fully vaccinated women in the same deprivation group was 0.29 (95% CI 0.2 to 0.43) compared with 0.62 (95% CI 0.4 to 0.97) in vaccinated women in the least-deprived group. The HPV vaccine is associated with significant reductions in both low-grade and high-grade CIN for all deprivation categories. However, the effect on high-grade disease was most profound in the most-deprived women. These data are welcoming and allay the concern that inequalities in cervical cancer may persist or increase following the introduction of the vaccine in Scotland. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Lack of commensal flora in H. pylori-infected INS-GAS mice reduces gastritis and delays intraepithelial neoplasia

PubMed Central

Lofgren, Jennifer L.; Whary, Mark T.; Ge, Zhongming; Muthupalani, Sureshkumar; Taylor, Nancy S.; Mobley, Melissa; Potter, Amanda; Varro, Andrea; Eibach, Daniel; Suerbaum, Sebastian; Wang, Timothy C.; Fox, James G.

2010-01-01

Background & Aims Transgenic, insulin–gastrin (INS–GAS) mice have high circulating levels of gastrin. On a FVB/N background, these mice develop spontaneous atrophic gastritis and gastrointestinal intraepithelial neoplasia (GIN) with 80% prevalence 6 months after Helicobacter pylori infection. GIN is associated with gastric atrophy and achlorhydria, predisposing mice to non-helicobacter microbiota overgrowth. We determined if germ-free INS–GAS mice spontaneously develop GIN and if H. pylori accelerates GIN in gnotobiotic INS–GAS mice. Methods We compared gastric lesions and levels of mRNA, serum inflammatory mediators, antibodies, and gastrin among germ-free and H. pylori-monoinfected INS-GAS mice. Microbiota composition of specific pathogen-free (SPF) INS-GAS mice was quantified by pyro-sequencing. Results Germ-free INS-GAS mice had mild hypergastrinemia but did not develop significant gastric lesions until they were 9 months old; they did not develop GIN through 13 months. H. pylori monoassociation caused progressive gastritis, epithelial defects, oxyntic gland atrophy, marked foveolar hyperplasia and dysplasia, and strong serum and tissue proinflammatory immune responses (particularly in male mice) between 5 and 11 months post infection (P<0.05, compared with germ-free controls). Only 2 of 26 female, whereas 8 of 18 male, H. pylori-infected INS-GAS mice developed low- to high-grade GIN by 11 months post infection. Stomachs of H. pylori-infected SPF male mice had significant reductions in Bacteroidetes and significant increases in Firmicutes. Conclusions Gastric lesions take 13 months longer to develop in germ-free INS–GAS mice than male SPF INS-GAS mice. H. pylori-monoassociation accelerated gastritis and GIN but caused less-severe gastric lesions and delayed onset of GIN compared to H. pylori-infected INS-GAS mice with complex gastric microbiota. Changes of gastric microbiota composition might promote GIN in the achlorhydric stomachs of SPF mice. PMID

Association of Genital Infections Other Than Human Papillomavirus with Pre-Invasive and Invasive Cervical Neoplasia

PubMed Central

Mandal, Ranajit; Kundu, Pratip; Biswas, Jaydip

2016-01-01

Human papillomavirus (HPV) is a well-established causative agent of malignancy of the female genital tract and a common Sexually Transmitted Infection. The probable co-factors that prevent spontaneous clearance of HPV and progression to neoplasia are genital tract infections from organisms like Chlamydia, Trichomonas vaginalis etc, smoking, nutritional deficiencies and multiparity. Inflammatory conditions can lead to pre-neoplastic manifestations in the cervical epithelium; however their specific role in cervical carcinogenesis is not yet established. Therefore it is imperative to study the likely association between HPV and co-infection with various common pathogens in the genital tract of women having cervical precancer or cancer. A “Pubmed” search was made for articles in Literature on this topic using the words: Cervical neoplasia, HPV, co-infections, Cervical Intraepithelial Neoplasia (CIN), Trichomonas vaginalis, Candida, Chlamydia and the relevant information obtained was used to draft the review. PMID:27042571

High-risk human papilloma virus management in pregnancy with cervical intraepithelial neoplasia during pregnancy and postpartum in China.

PubMed

He, Yue; Wu, Yu-Mei; Zhao, Qun; Wang, Tong; Song, Fang; Zhu, Li

2014-02-01

To investigate the relationship between cervical intraepithelial neoplasia (CIN) and high-risk human papilloma virus (HR-HPV) during pregnancy and postpartum in China. In this prospective case-control study, 168 pregnant women with CIN and cervicitis were diagnosed by colposcopic cervical biopsy. All the cases underwent hybrid capture assay version II (HCII) to detect HR-HPV DNA load amounts and the tests were completed in 3-6 months after childbirth. During pregnancy: as the CIN grade increased, the HR-HPV infection rates increased (P = 0.002), but HR-HPV DNA load amounts (in logarithms) did not change obviously (P = 0.719). 3-6 months postpartum: as the CIN grade increased, the natural negative rate of HR-HPV decreased (P = 0.000), while the amount of HR-HPV DNA (in logarithms) increased (P = 0.036); especially the amount of HR-HPV DNA in pregnant women with CINIII was significantly higher than that of other grades. During pregnancy and 3-6 months postpartum : the amount of HR-HPV DNA (in logarithms) during pregnancy was higher than that of 3-6 months postpartum with the same grade of CIN. The findings emphasize the importance of undergoing the HCII test 3-6 months postpartum. It should be noted that HR-HPV may turn negative in pregnancy with CINIII 3-6 months after childbirth. Further treatments of pregnancy with CIN should be considered according to the CIN grade diagnosed by cervical biopsy via colposcopy 3-6 months after birth, but not according to the persistence of HR-HPV during pregnancy. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

Role of the human papilloma virus in the development of cervical intraepithelial neoplasia and malignancy.

PubMed

Jastreboff, A M; Cymet, T

2002-04-01

Human papilloma virus (HPV) is a public health problem as a sexually transmitted disease and as a critical factor in the pathogenesis of various cancers. The clinical manifestations, epidemiology, and virology that are critical to understanding the process of cervical dysplasia and neoplasia are reviewed. A discussion of the cervical transformation zone and the classification of cervical dysplasia and neoplasia leads into the importance of the Papanicolaou smear in prevention of potentially devastating sequelae of this virus. The role of the immune system in the progression of the disease and how it relates to vaccines, as well as treatment and prevention of HPV, are reviewed.

Role of the human papilloma virus in the development of cervical intraepithelial neoplasia and malignancy

PubMed Central

Jastreboff, A; Cymet, T

2002-01-01

Human papilloma virus (HPV) is a public health problem as a sexually transmitted disease and as a critical factor in the pathogenesis of various cancers. The clinical manifestations, epidemiology, and virology that are critical to understanding the process of cervical dysplasia and neoplasia are reviewed. A discussion of the cervical transformation zone and the classification of cervical dysplasia and neoplasia leads into the importance of the Papanicolaou smear in prevention of potentially devastating sequelae of this virus. The role of the immune system in the progression of the disease and how it relates to vaccines, as well as treatment and prevention of HPV, are reviewed. PMID:11930025

Evidence supporting see-and-treat management of cervical intraepithelial neoplasia: a systematic review and meta-analysis.

PubMed

Ebisch, R M F; Rovers, M M; Bosgraaf, R P; van der Pluijm-Schouten, H W; Melchers, W J G; van den Akker, P A J; Massuger, L F A G; Bekkers, R L M

2016-01-01

Studies of see-and-treat management of cervical intraepithelial neoplasia (CIN) vary in their inclusion criteria, resulting in a broad range of overtreatment rates. To determine overtreatment rates in see-and-treat management of women referred for colposcopy because of suspected CIN, in order to define circumstances supporting see-and-treat management. MEDLINE, EMBASE, and the Cochrane Library were searched from inception up to 12 May 2014. Studies of see-and-treat management in women with a reported cervical smear result, colposcopic impression, and histology result were included. Methodological quality was assessed with the Newcastle-Ottawa scale. We used the inverse variance method for pooling incidences, and a random-effects model was used to account for heterogeneity between studies. Overtreatment was defined as treatment in patients with no CIN or CIN1. Thirteen studies (n = 4611) were included. The overall overtreatment rate in women with a high-grade cervical smear and a high-grade colposcopic impression was 11.6% (95% CI 7.8-15.3%). The overtreatment rate in women with a high-grade cervical smear and low-grade colposcopic impression was 29.3% (95% CI 16.7-41.9%), and in the case of a low-grade smear and high-grade colposcopic impression it was 46.4% (95% CI 15.7-77.1%). In women with a low-grade smear and low-grade colposcopic impression, the overtreatment rate was 72.9% (95% CI 68.1-77.7%). The pooled overtreatment rate in women with a high-grade smear and high-grade colposcopic impression is at least comparable with the two-step procedure, which supports the use of see-and-treat management in this subgroup of women. See-and-treat management is justified in the case of a high-grade smear and a high-grade colposcopic impression. © 2015 Royal College of Obstetricians and Gynaecologists.

Posttreatment human papillomavirus testing for residual or recurrent high-grade cervical intraepithelial neoplasia: a pooled analysis

PubMed Central

Yoshikawa, Hiroyuki

2016-01-01

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. PMID:26463429

Revised terminology for cervical histopathology and its implications for management of high-grade squamous intraepithelial lesions of the cervix.

PubMed

Waxman, Alan G; Chelmow, David; Darragh, Teresa M; Lawson, Herschel; Moscicki, Anna-Barbara

2012-12-01

In March 2012, the College of American Pathologists and American Society for Colposcopy and Cervical Pathology, in collaboration with 35 stakeholder organizations, convened a consensus conference called the Lower Anogenital Squamous Terminology (LAST) Project. The recommendations of this project include using a uniform, two-tiered terminology to describe the histology of human papillomavirus-associated squamous disease across all anogenital tract tissues: vulva, vagina, cervix, penis, perianus, and anus. The recommended terminology is "low-grade" or "high-grade squamous intraepithelial lesion (SIL)." This terminology is familiar to clinicians, because it parallels the terminology of the Bethesda System cytologic reports. Biopsy results using SIL terminology may be further qualified using "intraepithelial neoplasia" (IN) terminology in parentheses. Laboratory p16 tissue immunostaining is recommended to better classify histopathology lesions that morphologically would earlier have been diagnosed as IN 2. p16 is also recommended for differentiating between high-grade squamous intraepithelial lesions and benign mimics. The LAST Project recommendations potentially affect the application of current guidelines for managing cervical squamous intraepithelial lesions. The authors offer interim guidance for managing cervical lesions diagnosed using this new terminology with special attention paid to managing young women with cervical high-grade squamous intraepithelial lesions on biopsy. Clinicians should be aware of the LAST Project recommendations, which include important changes from prior terminology.

CD34(+) fibrocytes in normal cervical stroma, cervical intraepithelial neoplasia III, and invasive squamous cell carcinoma of the cervix uteri.

PubMed

Barth, Peter J; Ramaswamy, Annette; Moll, Roland

2002-12-01

CD34(+) fibrocytes are widely distributed in normal connective tissues but have been reported to be absent within the stroma associated with invasive carcinomas. In the present study we investigated the presence and distribution of CD34(+) fibrocytes and alpha-smooth muscle actin (alpha-SMA) positive myofibroblasts in cervical intraepithelial neoplasia III (CIN III; n=8), invasive carcinoma of the cervix ( n=18) and adjacent normal cervical stroma. Normal cervical stroma and the stroma adjacent to CIN III disclosed a dense network of CD34(+) fibrocytes, whereas the stroma of invasive carcinoma was virtually free of this cell population. Early stromal invasion by squamous carcinoma was characterized by a focal loss of CD34(+) fibrocytes. alpha-SMA-positive myofibroblasts were not seen in the normal cervical stroma but occurred in six of eight cases of CIN III adjacent to the atypical epithelium. The stroma of invasive carcinoma was made up of large amounts of haphazardly arranged alpha-SMA-positive myofibroblasts. In the setting of the present study, a loss of CD34(+) fibrocytes was specific for stromal alterations associated with invasive carcinoma and proved to be a sensitive tool in detecting small foci of stromal invasion. Therefore, detection of a loss of CD34(+) fibrocytes may constitute an adjunctive tool in detecting (1) early stromal invasion and (2) invasive carcinoma in small biopsy specimens. Moreover, the present study shows that CD34(+) fibrocytes and myofibroblasts play an important role in stromal remodeling associated with invasive squamous cell carcinoma of the cervix.

Does the vaginal microbiota play a role in the development of cervical cancer?

PubMed

Kyrgiou, Maria; Mitra, Anita; Moscicki, Anna-Barbara

2017-01-01

Persistent infection with oncogenic human papillomavirus (HPV) is necessary but not sufficient for the development of cervical cancer. The factors promoting persistence as well those triggering carcinogenetic pathways are incompletely understood. Rapidly evolving evidence indicates that the vaginal microbiome (VM) may play a functional role (both protective and harmful) in the acquisition and persistence of HPV, and subsequent development of cervical cancer. The first studies examining the VM and the presence of an HPV infection using next-generation sequencing techniques identified higher microbial diversity in HPV-positive as opposed to HPV-negative women. Furthermore, there appears to be a temporal relationship between the VM and HPV infection in that specific community state types may be correlated with a higher chance of progression or regression of the infection. Studies describing the VM in women with preinvasive disease (squamous intraepithelial neoplasia [SIL]) consistently demonstrate a dysbiosis in women with the more severe disease. Although it is plausible that the composition of the VM may influence the host's innate immune response, susceptibility to infection, and the development of cervical disease, the studies to date do not prove causality. Future studies should explore the causal link between the VM and the clinical outcome in longitudinal samples from existing biobanks. Copyright © 2016 Elsevier Inc. All rights reserved.

Anal intraepithelial neoplasia in the highly active antiretroviral therapy era among HIV-positive men who have sex with men.

PubMed

Palefsky, Joel M; Holly, Elizabeth A; Efirdc, Jimmy T; Da Costa, Maria; Jay, Naomi; Berry, J Michael; Darragh, Teresa M

2005-09-02

The incidence of anal cancer among men who have sex with men (MSM) has continued to increase since the introduction of highly active antiretroviral therapy (HAART). The prevalence of the putative anal cancer precursor, anal intraepithelial neoplasia (AIN) was high among HIV-positive MSM prior to the availability of HAART but little is known about AIN since HAART was introduced. We characterized the prevalence of AIN among HIV-positive MSM and examined the association between AIN and various factors including use of HAART. A baseline point-prevalence analyses in a prospective cohort study of AIN was performed at a university-based research clinic. A total of 357 HIV-positive MSM with no history of anal cancer completed a questionnaire detailing behaviors and medical history, anal cytology and human papillomavirus (HPV) testing, and high-resolution anoscopy with biopsy for detection of AIN. Eighty-one percent of participants with available CD4+ cell counts at baseline had AIN of any grade; 52% had AIN 2 or 3; and 95% had anal HPV infection. In multivariate analysis, detection of > or = 6 HPV types [odds ratio (OR), 36; 95% confidence interval (CI), 7.4-171) and use of HAART (OR, 10; 95% CI, 2.6-38) were associated with AIN after adjustment for length of time participants were HIV-positive, CD4+ cell count and HIV viral load. The prevalence of AIN has remained high among HIV-positive MSM after the introduction of HAART. Our data indicate that HAART is not associated with a reduced prevalence of AIN and support measures to prevent anal cancer among HIV-positive MSM whether or not they are using HAART.

Cervical HIV-1 RNA shedding after cryotherapy among HIV-positive women with cervical intraepithelial neoplasia stage 2 or 3

PubMed Central

Chung, Michael H.; McKenzie, Kevin P.; Richardson, Barbra A.; John-Stewart, Grace C.; Coombs, Robert W.; Vuyst, Hugo De; Njoroge, Julia W.; Nyongesa-Malava, Evans; Sakr, Samah R.; Mugo, Nelly R.

2011-01-01

Objective To determine the effect of cryotherapy on HIV-1 cervical shedding. Design Prospective cohort study. Methods Five hundred HIV-positive women enrolled at an HIV treatment clinic in Nairobi, Kenya were screened for cervical cancer. Women diagnosed with cervical intraepithelial neoplasia stage 2 or 3 (CIN 2/3) by histology were offered cryotherapy treatment. The first 50 women had cervical swabs taken at baseline and at 2 and 4 weeks following treatment. Swabs were analyzed for HIV-1 RNA and compared using General Estimating Equation (GEE) with binomial or Gaussian links. Results Of the 50 women enrolled, 40 were receiving antiretroviral therapy (ART) and 10 were not receiving ART at the time of cryotherapy and during study follow-up. Among all women, the odds of detectable cervical HIV-1 RNA did not increase at 2 weeks [odds ratio (OR) 1.18; 95% confidence interval (CI) 0.65–2.13] or 4 weeks (OR 1.29; 95% CI 0.71–2.33) following cryotherapy. Among 10 women not receiving ART, the OR of detectable shedding at 2 weeks was higher, but not statistically significant (OR 4.02; 95% CI 0.53–30.79; P = 0.2), and at 4 weeks remained unchanged (OR 1.00; 95% CI 0.27–3.74). Conclusion There was no increase in detectable cervical HIV-1 RNA among HIV-positive women after cryotherapy. The risk of HIV-1 transmission after cryotherapy may not be significant, particularly among women already on ART at the time of cervical treatment. However, further investigation is needed among women not receiving ART. PMID:21716072

Highly differentiated keratinizing squamous cell cancer of the cervix: a rare, locally aggressive tumor not associated with human papillomavirus or squamous intraepithelial lesions.

PubMed

Morrison, C; Catania, F; Wakely, P; Nuovo, G J

2001-10-01

The purpose of this study is to report an unusual variant of cervical squamous cell carcinoma, not associated with either human papillomavirus infection or antecedent squamous intraepithelial lesions. Five women had a diagnosis of invasive cervical cancer discovered at hysterectomy performed for prolapse (two cases), leiomyoma (one case), or a vaginal fistula (two cases). The women ranged in age from 47 to 78 years (mean 59 years). Four of the five had a history of normal Papanicolaou (Pap) smears; the other had a Pap smear diagnosis of atypical squamous cells of undetermined significance (ASCUS). All had large cervical tumors (two with parametrial involvement and one with vaginal involvement) that showed extensive keratin formation, an inverted pattern of growth, and, except for one case, minimal cytologic atypia. There was extensive hyperkeratosis and parakeratosis adjacent to each tumor; none had evidence of squamous intraepithelial lesion. Human papillomavirus testing by polymerase chain reaction in situ hybridization and reverse-transcribed polymerase chain reaction in situ was negative in each case, compared with a detection rate of 107 of 108 (99%) for squamous intraepithelial lesion-associated cervical squamous cell and adenocarcinomas. Two of the women died of extensive local recurrence; two other women were recently diagnosed. We conclude that highly differentiated keratinizing squamous cell carcinoma of the cervix is a rare entity not associated with human papillomavirus infection or squamous intraepithelial lesion and thus difficult to detect on routine cervical cancer screening.

Incidence of High Grade Squamous Intraepithelial Lesions in Patients with Atypical Squamous Cells of Undetermined Significance Papanicolaou Smears at Naresuan University Hospital.

PubMed

Heng, Suttichai; Sirichaisutdhikorn, Daranee

2016-01-01

To determine the incidence of high-grade cervical intraepithelial neoplasia (CIN2-3) among patients with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou (Pap) smears. One-hundred and eighty-seven patients with ASC-US Pap smears who underwent colposcopy with histological study were enrolled between September 2007 and August 2015. Patient factors (including age, parity, current pills used, HIV status, age at first sexual intercourse and number of sexual partners) were obtained. Logistic regression analysis was used to evaluate clinical factors associated with CIN2-3. CIN was diagnosed in 92 of 187 women (49.2%). Sixty-one of these (32.6%) had CIN1 and 31 (16.6%) had CIN2-3. There was no woman who had invasive cancer. There was no correlation of high-grade CIN with factors in this study including age, parity, current pills used, HIV status, age at first sexual intercourse and number of sexual partners. Data from this study showed no invasive cervical cancer was found in patients with ASC-US. There was no patient factor associated with high grade intraepithelial neoplasia in patients with ASC-US Pap smears.

Presence of koilocytosis in low-grade smears of high-risk HPV-positive women is a negative predictor for cervical intraepithelial neoplasia grade 3 or more.

PubMed

Siebers, A G; van der Linden, H; Vedder, J E M; Bekkers, R L M; Melchers, W L G; Bulten, J

2018-03-25

The Netherlands converted to high-risk (hr)HPV-based screening in 2017. An increase in referral of hrHPV-positive women with low risk for cervical intraepithelial neoplasia grade 3 or more (CIN3+) is anticipated and reduction of unjustified referrals will have priority. The relevance of koilocytosis in relation to the underlying risk of high-grade CIN in a primary HPV screening setting is unclear. The aim was to investigate whether the risk for CIN3+ differs between hrHPV-positive atypical squamous cells of undetermined significance (ASC-US)/low-grade squamous intraepithelial lesion (LSIL) with or without koilocytosis. Retrospective cohort study, using data from the Dutch national pathology database (PALGA). The population was 1201 hrHPV-positive women with cytological diagnosis of ASC-US/LSIL. Reporting of koilocytosis was assessed as well as detection rates of CIN1 or less, CIN2 and CIN3+ for ASC-US/LSIL cytology stratified by presence or absence of koilocytosis. Crude and adjusted odds ratios were determined. Koilocytosis was present in 40.1% of ASC-US and 45.9% of LSIL cases. CIN3+ is significantly less often found when koilocytosis is present (7.8% for hrHPV-positive ASC-US with- vs 15.8% without koilocytosis). For hrHPV-positive LSIL this was 11.7% vs 20.2%. The crude and adjusted odds ratios for CIN3+ was 0.45 for hrHPV-positive ASC-US and 0.52 for hrHPV-positive LSIL. The presence of koilocytosis is a negative predictor of CIN3+. The risk of hrHPV-positive ASC-US with koilocytosis is in the same range as hrHPV-positive/cytology negative cases and in a setting of primary hrHPV screening these cases could be followed conservatively by repeat cytology. The results should be confirmed by the first data from the Dutch HPV-based screening programme. © 2018 John Wiley & Sons Ltd.

Longitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: critical role of duration of infection.

PubMed

Rodríguez, Ana Cecilia; Schiffman, Mark; Herrero, Rolando; Hildesheim, Allan; Bratti, Concepción; Sherman, Mark E; Solomon, Diane; Guillén, Diego; Alfaro, Mario; Morales, Jorge; Hutchinson, Martha; Katki, Hormuzd; Cheung, Li; Wacholder, Sholom; Burk, Robert D

2010-03-03

The natural history of human papillomavirus (HPV) infections in older women is critical for preventive strategies, including vaccination and screening intervals, but is poorly understood. In a 7-year population-based cohort study in Guanacaste, Costa Rica, we examined whether women's age and the duration of carcinogenic HPV infections influenced subsequent persistence of infection and risk of cervical intraepithelial neoplasia grade 2 (CIN 2) or worse disease. At enrollment, of the 9466 participants eligible for pelvic examination, 9175 were screened for cervical neoplasia using multiple methods; those with CIN 2 or worse disease were censored and treated. Participants at low risk of CIN 2 or worse (n = 6029) were rescreened at 5-7 years (passively followed), whereas higher-risk participants (n = 2115) and subsets of low-risk women (n = 540) and initially sexually inactive women (n = 410) were rescreened annually or semiannually (actively followed) for up to 7 years. HPV testing was done using a polymerase chain reaction-based method. We determined, by four age groups (18-25, 26-33, 34-41, and > or =42 years), the proportion of prevalent infections (found at baseline) and newly detected infections (first found during follow-up) that persisted at successive 1-year time points and calculated absolute risks of CIN 2 and CIN grade 3 (CIN 3) or worse during follow-up. P values are two-sided. Regardless of the woman's age, newly detected infections were associated with very low absolute risks of persistence, CIN 2, or worse disease. For newly detected infections, the rate of progression to CIN 2+ (or CIN 3+), after 3 years of follow-up, was not higher for women aged 34 years and older than for younger women. Moreover, rates of newly detected infections declined sharply with age (in the actively followed group, at ages 18-25, 26-33, 34-41, and > or =42 years, rates were 35.9%, 30.6%, 18.1%, and 13.5%, respectively; P < .001). Among prevalent infections, persistent

Effectiveness of systematic alphanumeric coded endoscopy for diagnosis of gastric intraepithelial neoplasia in a low socioeconomic population.

PubMed

Machaca Quea, Nancy Roxana; Emura, Fabian; Barreda Bolaños, Fernando; Salvador Arias, Yuliana; Arévalo Suárez, Fernando Antonio; Piscoya Rivera, Alejandro

2016-10-01

Background and study aims: In the Western world, gastric cancer (GC) usually presents at an advanced stage, carrying a high mortality rate. Studies have reported that 14 % to 26 % of GCs are missed at endoscopy up to 3 years before diagnosis. Systematic Alphanumeric Coded Endoscopy (SACE) has been proposed to improve quality of esophagogastroduodenoscopy (EGD) by facilitating a complete examination of the upper gastrointestinal tract. This prospective cross-sectional study was designed to determine the frequency of gastric intraepithelial neoplasia (GIN) by using the SACE approach in cohort of patients from low socioeconomic level. It also used non-targeted biopsies to evaluate the frequency of premalignant conditions. Patients and methods: A total of 601 consecutive asymptomatic or dyspeptic patients were enrolled between January 2013 and November 2014 at the Huacho regional hospital in Peru. The SACE method proposed by Emura et al, which divides the stomach into 5 regions and 21 areas, was routinely used for diagnosis. Biopsy samples were obtained from any endoscopically detected focal lesion. To evaluate gastric premalignant conditions, 4 non-targeted biopsies were taken. Results: A total of 573 patients were analyzed. The mean age was 57 years, and the female:male ratio was 1.9 : 1. In all cases, complete photo-documentation of the 21 gastric areas was achieved. The overall rate of detection of GIN was 2.8 %. Low-grade displasia, high-grade dysplasia, and adenocarcinoma were found in 13 (2.3 %), 2 (0.3 %), and 1 (0.2 %) of the patients, respectively. The prevalence of at least 1 premalignant condition was 31 %, and helicobacter pylori infection was found in 57 % of patients. Conclusions: Using the SACE approach and with proper training, we have reported herein a high frequency of GIN in patients from a low socioeconomic status. Gastric cancer detection can be improved in a Western endoscopy setting when SACE, as a screening method, is

Effectiveness of systematic alphanumeric coded endoscopy for diagnosis of gastric intraepithelial neoplasia in a low socioeconomic population

PubMed Central

Machaca Quea, Nancy Roxana; Emura, Fabian; Barreda Bolaños, Fernando; Salvador Arias, Yuliana; Arévalo Suárez, Fernando Antonio; Piscoya Rivera, Alejandro

2016-01-01

Background and study aims: In the Western world, gastric cancer (GC) usually presents at an advanced stage, carrying a high mortality rate. Studies have reported that 14 % to 26 % of GCs are missed at endoscopy up to 3 years before diagnosis. Systematic Alphanumeric Coded Endoscopy (SACE) has been proposed to improve quality of esophagogastroduodenoscopy (EGD) by facilitating a complete examination of the upper gastrointestinal tract. This prospective cross-sectional study was designed to determine the frequency of gastric intraepithelial neoplasia (GIN) by using the SACE approach in cohort of patients from low socioeconomic level. It also used non-targeted biopsies to evaluate the frequency of premalignant conditions. Patients and methods: A total of 601 consecutive asymptomatic or dyspeptic patients were enrolled between January 2013 and November 2014 at the Huacho regional hospital in Peru. The SACE method proposed by Emura et al, which divides the stomach into 5 regions and 21 areas, was routinely used for diagnosis. Biopsy samples were obtained from any endoscopically detected focal lesion. To evaluate gastric premalignant conditions, 4 non-targeted biopsies were taken. Results: A total of 573 patients were analyzed. The mean age was 57 years, and the female:male ratio was 1.9 : 1. In all cases, complete photo-documentation of the 21 gastric areas was achieved. The overall rate of detection of GIN was 2.8 %. Low-grade displasia, high-grade dysplasia, and adenocarcinoma were found in 13 (2.3 %), 2 (0.3 %), and 1 (0.2 %) of the patients, respectively. The prevalence of at least 1 premalignant condition was 31 %, and helicobacter pylori infection was found in 57 % of patients. Conclusions: Using the SACE approach and with proper training, we have reported herein a high frequency of GIN in patients from a low socioeconomic status. Gastric cancer detection can be improved in a Western endoscopy setting when SACE, as a screening method, is

Karyometry detects subvisual differences in chromatin organization state between cribriform and flat high-grade prostatic intraepithelial neoplasia.

PubMed

Montironi, Rodolfo; Thompson, Deborah; Scarpelli, Marina; Mazzucchelli, Roberta; Peketi, Prasanthi; Hamilton, Peter W; Bostwick, David G; Bartels, Peter H

2004-08-01

This digital texture analysis-based study evaluates the chromatin organization state in flat and cribriform high-grade prostatic intraepithelial neoplasia (PIN), in the adjacent normal looking secretory epithelium and in the co-occurring adenocarcinoma. Digital texture analysis (karyometry) was carried out on hematoxylin and eosin-stained sections from 24 radical prostatectomy specimens with high-grade PIN (12 with flat and 12 with cribriform architectural pattern, respectively) and cancer. Quantification was also conducted on the normal looking secretory epithelium. Discriminant analysis and the nonsupervised learning algorithm P-index were used to identify suitable subsets of features useful for the discrimination and classification of pathological groups and to explore multivariate data structure in the pathological subgroups. The average nuclear abnormality increases monotonically from the histologically normal appearing secretory epithelium to high-grade PIN and to adenocarcinoma. The nuclei from the so-called perimeter compartment of the flat high-grade PIN lesions show a higher nuclear abnormality compared to the nuclei of the cribriform high-grade PINs. Discriminant analysis shows that flat and cribriform high-grade PINs fall into two populations. Processing by the nonsupervised learning algorithm P-index revealed the existence of three well-defined, distinct subpopulations of nuclei of different chromatin phenotype. In the flat high-grade PIN lesions the proportions of nuclei in the three subpopulations are 16.5% (low abnormality), 25.0% (mid abnormality) and 58.5% (high abnormality), respectively. In the cribriform high-grade PIN lesions, 100% of the nuclei are in the mid-abnormality subpopulation. These differences are also discernible in the co-occurring adenocarcinoma and the histologically normal appearing secretory epithelium. To conclude, karyometry and statistical analysis detect the existence of distinct cell subpopulations of different chromatin

Differential expression of cytokeratin mRNA and protein in normal prostate, prostatic intraepithelial neoplasia, and invasive carcinoma.

PubMed Central

Yang, Y.; Hao, J.; Liu, X.; Dalkin, B.; Nagle, R. B.

1997-01-01

The expression of cytokeratin (CK) mRNA for CK5, -8, -14, -16, and -19 was investigated in normal prostate, prostatic intraepithelial neoplasia (PIN) lesions, and invasive carcinoma using in situ hybridization. Protein localization was carried out in adjacent sections using immunohistochemistry and correlated with mRNA expression. Snap-frozen human prostate samples including 22 examples of normal glands, 20 cases of PIN lesions, and 12 cases of invasive carcinoma were examined. CK5 and -14 mRNA and protein were prominently expressed only in the basal cells of normal glands and PIN lesions. CK14 mRNA was absent in the luminal cells of the most of the PIN lesions but was seen at a low level in some PIN lesions. CK14 protein was not detected in any PIN lesion, suggesting that, if the cell that makes up the PIN lesions is derived from a basal cell, CK14 translation is depressed although a low level of CK14 mRNA may persist. CK8 mRNA and protein were constitutively expressed in all epithelia of normal and abnormal prostate tissues. CK19 mRNA and protein were persistently expressed in both basal and luminal cells of the tubular portion of normal glands as well as PIN lesions, but were expressed heterogeneously in both basal and luminal cells of normal alveoli. CK16 mRNA was expressed in a similar pattern as CK19, but CK16 protein was not detected either in normal or in abnormal prostate tissues. In conclusion, the expression of CK19 in PIN lesions is similar to its tubular expression and would support an origin of PIN lesions from this structure rather than the alveolar portion of the glands. The similar cytokeratin expression between PIN lesions and invasive carcinoma further supports the concept that PIN is a precursor lesion of invasive carcinoma. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:9033282

Pancreatic intraepithelial neoplasia in association with intraductal papillary mucinous neoplasms of the pancreas: implications for disease progression and recurrence.

PubMed

Biankin, Andrew V; Kench, James G; Biankin, Sandra A; Lee, C-Soon; Morey, Adrienne L; Dijkman, Floriaan P; Coleman, Maxwell J; Sutherland, Robert L; Henshall, Susan M

2004-09-01

The development of pancreatic cancer (PC) several years after curative resection for noninvasive intraductal papillary mucinous neoplasm (IPMN) and the presence of PC distant from IPMN suggest that PC may develop independently of the IPMN. Here, we identified pancreatic intraepithelial neoplasia (PanIN) lesions, the putative precursors of PC, in the ducts of pancreata resected for IPMN and assessed the frequency of molecular aberrations common to PanIN and PC, within these lesions. The protein expression of p53, p21(WAF1/CIP1), cyclin D1, p16(INK4A) and DPC4/Smad4 were examined by immunohistochemistry in 267 PanIN lesions from a cohort of 23 patients with IPMN. Overexpression of p21(WAF1/CIP1) was present in PanIN-1A and -1B lesions and increased in frequency in PanIN-2 and PanIN-3. Overexpression of p53 and cyclin D1, and loss of p16(INK4A) expression were detected in PanIN-2 and PanIN-3 lesions. Loss of DPC4/Smad4 expression occurred only in the PanIN-3 lesions. PanIN lesions that were more dysplastic than the coincident IPMN were identified in 5 of 12 patients, and 2 of these contained a greater number of aberrations in protein expression than the IPMN. PanIN lesions seen in association with IPMN demonstrate molecular and histologic changes identical to PanIN lesions found in association with PC and, in some cases, are more advanced than the associated IPMN. These data suggest that PanIN lesions found in the ducts of a pancreas with IPMN may be relevant to the development of PC either coincident with IPMN or in the remnant pancreas after curative resection of IPMN.

The role of oncogenic human papillomavirus determination for diagnosis of high-grade anal intraepithelial neoplasia in HIV-infected MSM.

PubMed

Burgos, Joaquin; Hernández-Losa, Javier; Landolfi, Stefania; Guelar, Ana; Dinares, MªCarmen; Villar, Judith; Navarro, Jordi; Ribera, Esteve; Falcó, Vicenç; Curran, Adria

2017-10-23

To assess the oncogenic human papillomavirus (HPV) determination and the cotesting HPV and anal cytology value to detect high-grade anal intraepithelial neoplasia (HGAIN) in a cohort of HIV-MSM. Prospective study of HIV-infected MSM who underwent screening for anal dysplasia. Screening program includes anal cytology, HPV testing, and high-resolution anoscopy (HRA) at each visit. Histological samples were obtained if suspicious lesions were revealed by HRA. Sensitivity and specificity of the different tests were calculated by using histological results of HRA-guided biopsy as the reference test for HGAIN diagnosis. From May 2009 to August 2016, 692 HIV-infected MSM underwent 1827 anal cytologies, 1841 HRA examinations, and 1607 HPV testing. At first screening visit, anal cytology results were abnormal in 418 (60.4%) of 692 patients, and oncogenic HPV genotypes were found in 482 (79.5%) of 606 patients. Anal cytology showed a sensitivity of 89.2% [95% confidence interval (CI); 80.7-94.2] and a specificity of 44.2% (95% CI; 40.2-48.2) to detect HGAIN. Oncogenic HPV testing had 90.4% sensitivity (95% CI; 82-86.8) and 24.4% specificity (95% CI; 20.8-28.3). Cotesting showed a 97.4% sensitivity (95% CI; 91-99.3) and 14% specificity (95% CI; 11.2-17.3). In patients with atypical squamous cells of uncertain significance on cytology, oncogenic HPV testing had 91.3% sensitivity and 28.3% specificity to detect HGAIN. Abnormal cytology and oncogenic HPV determination showed similar sensitivity for detecting HGAIN. The two tests used together improved the sensitivity but with lowered specificity. In our opinion, HPV testing does not improve HGAIN detection and should not replace anal cytology as a standard screening test for HIV-infected MSM.

Significance of lobular intraepithelial neoplasia at margins of breast conservation specimens: a report of 38 cases and literature review

PubMed Central

2010-01-01

Background Presence of lobular intraepithelial neoplasia (LIN) is not routinely reported as part of margin assessment in breast conservation therapy (BCT) as in ductal carcinoma in situ (DCIS). With new emerging evidence of LIN as possible precursor lesion, the hypothesis is that LIN at the margin may increase the risk of local recurrence with BCT. The aim is to determine whether there is an increase incidence of recurrence when LIN is found at surgical margins on BCT. Methods We retrospectively reviewed a total of 1,334 BCT at a single institution in a 10 year period. Inclusion criteria are positive margin with LIN from primary BCT containing invasive and/or in situ carcinoma with comparison to the negative control group who had similar diseases with negative margin for LIN. Results We identified 38 cases (2.8%) with LIN either lobular carcinoma in situ/atypical lobular hyperplasia (LCIS/ALH) at a margin on initial BCT with 36% recurrence rate. Of the 38 cases: 5 (13%) were lost to follow-up, 12 (32%) had no further procedures performed and 21 (55%) had re-excision. Out of 21 patients who had re-excisions, 12 (57%) had residual invasive carcinoma or DCIS, three (14%) had pleomorphic LCIS and 4 (19%) showed residual classic type LCIS. 71% had significant residual disease (local recurrence) and 29% had no residual disease. A negative control group consisted of 38 cases. We found two patients with bone or brain metastasis and one local recurrence. Clinical follow up periods range from 1 to 109 months. Conclusions LIN found at a margin on BCT showed a significant recurrent ipsilateral disease. Our study supports the view that LIN seen at the margin may play a role in recurrence. PMID:20727142

Genotype distribution of human papillomavirus (HPV) in histological sections of cervical intraepithelial neoplasia and invasive cervical carcinoma in Madrid, Spain

PubMed Central

2012-01-01

Background Human Papillomavirus (HPV) genotype distribution and co-infection occurrence was studied in cervical specimens from the city of Madrid (Spain), as a contribution to the knowledge of Human Papillomavirus genotype distribution and prevalence of carcinogenic HPV types in cervical lesions in Spain. Methods A total of 533 abnormal specimens, from the Hospital General Universitario “Gregorio Marañón” of Madrid, were studied. These included 19 benign lesions, 349 cervical intraepithelial neoplasias 1 (CIN1), 158 CIN2-3 and 7 invasive cervical carcinomas (ICC). HPV genotyping was performed using PCR and tube array hybridization. Results We detected 20 different HPV types: 13 carcinogenic high-risk HPV types (HR-HPVs), 2 probably carcinogenic high-risk HPV types (PHR-HPVs) and 5 carcinogenic low-risk HPV types (LR-HPVs). The most frequent HPV genotypes found in all specimens were HPV16 (26.0%), 31 (10.7%) and 58 (8.0%). HPV 18 was only detected in 5.0%. Co-infections were found in 30.7% of CIN 1 and 18.4% cases of CIN2-3. The highest percentage of HR HPVs was found in those specimens with a CIN2-3 lesion (93.7%). Conclusion As our study shows the current tetravalent vaccine could be effective in our geographical area for preventing all the invasive cervical carcinomas. In addition, upon the estimates of the important presence of other HR-HPV types – such as 31, 58, 33 and 52 – in different preneoplasic lesions the effectiveness of HPV vaccination in our geographical area, and others with similar genotype distribution, should be limited. PMID:23167826

Expression of the CXCL12/CXCR4 and CXCL16/CXCR6 axes in cervical intraepithelial neoplasia and cervical cancer

PubMed Central

Huang, Yu; Zhang, Jia; Cui, Zhu-Mei; Zhao, Jing; Zheng, Ye

2013-01-01

The chemokine CXCL12 is highly expressed in gynecologic tumors and is widely known to play a biologically relevant role in tumor growth and spread. Recent evidence suggests that CXCL16, a novel chemokine, is overexpressed in inflammation-associated tumors and mediates pro-tumorigenic effects of inflammation in prostate cancer. We therefore analyzed the expression of CXCL12 and CXCL16 and their respective receptors CXCR4 and CXCR6 in cervical intraepithelial neoplasia (CIN) and cervical cancer and further assessed their association with clinicopathologic features and outcomes. Tissue chip technology and immunohistochemistry were used to analyze the expression of CXCL12, CXCR4, CXCL16, and CXCR6 in healthy cervical tissue (21 cases), CIN (65 cases), and cervical carcinoma (60 cases). The association of protein expression with clinicopathologic features and overall survival was analyzed. These four proteins were clearly detected in membrane and cytoplasm of neoplastic epithelial cells, and their distribution and intensity of expression increased as neoplastic lesions progressed through CIN1, CIN2, and CIN3 to invasive cancer. Furthermore, the expression of CXCR4 was associated significantly with the histologic grade of cervical carcinoma, whereas the expression of CXCR6 was associated significantly with lymph node metastasis. In Kaplan-Meier analysis, patients with high CXCR6 expression had significantly shorter overall survival than did those with low CXCR6 expression. The elevated co-expression levels of CXCL12/CXCR4 and CXCL16/CXCR6 in CIN and cervical carcinoma suggest a durative process in cervical carcinoma development. Moreover, CXCR6 may be useful as a biomarker and a valuable prognostic factor for cervical cancer. PMID:22958742

Expression of the CXCL12/CXCR4 and CXCL16/CXCR6 axes in cervical intraepithelial neoplasia and cervical cancer.

PubMed

Huang, Yu; Zhang, Jia; Cui, Zhu-Mei; Zhao, Jing; Zheng, Ye

2013-05-01

The chemokine CXCL12 is highly expressed in gynecologic tumors and is widely known to play a biologically relevant role in tumor growth and spread. Recent evidence suggests that CXCL16, a novel chemokine, is overexpressed in inflammation-associated tumors and mediates pro-tumorigenic effects of inflammation in prostate cancer. We therefore analyzed the expression of CXCL12 and CXCL16 and their respective receptors CXCR4 and CXCR6 in cervical intraepithelial neoplasia (CIN) and cervical cancer and further assessed their association with clinicopathologic features and outcomes. Tissue chip technology and immunohistochemistry were used to analyze the expression of CXCL12, CXCR4, CXCL16, and CXCR6 in healthy cervical tissue (21 cases), CIN (65 cases), and cervical carcinoma (60 cases). The association of protein expression with clinicopathologic features and overall survival was analyzed. These four proteins were clearly detected in membrane and cytoplasm of neoplastic epithelial cells, and their distribution and intensity of expression increased as neoplastic lesions progressed through CIN1, CIN2, and CIN3 to invasive cancer. Furthermore, the expression of CXCR4 was associated significantly with the histologic grade of cervical carcinoma, whereas the expression of CXCR6 was associated significantly with lymph node metastasis. In Kaplan-Meier analysis, patients with high CXCR6 expression had significantly shorter overall survival than did those with low CXCR6 expression. The elevated co-expression levels of CXCL12/CXCR4 and CXCL16/CXCR6 in CIN and cervical carcinoma suggest a durative process in cervical carcinoma development. Moreover, CXCR6 may be useful as a biomarker and a valuable prognostic factor for cervical cancer.

Early diagnosis of pancreatic cancer: neutrophil gelatinase-associated lipocalin as a marker of pancreatic intraepithelial neoplasia

PubMed Central

Moniaux, N; Chakraborty, S; Yalniz, M; Gonzalez, J; Shostrom, V K; Standop, J; Lele, S M; Ouellette, M; Pour, P M; Sasson, A R; Brand, R E; Hollingsworth, M A; Jain, M; Batra, S K

2008-01-01

Pancreatic cancer is a highly lethal malignancy with a dismal 5-year survival of less than 5%. The scarcity of early biomarkers has considerably hindered our ability to launch preventive measures for this malignancy in a timely manner. Neutrophil gelatinase-associated lipocalin (NGAL), a 24-kDa glycoprotein, was reported to be upregulated nearly 27-fold in pancreatic cancer cells compared to normal ductal cells in a microarray analysis. Given the need for biomarkers in the early diagnosis of pancreatic cancer, we investigated the expression of NGAL in tissues with the objective of examining if NGAL immunostaining could be used to identify foci of pancreatic intraepithelial neoplasia, premalignant lesions preceding invasive cancer. To examine a possible correlation between NGAL expression and the degree of differentiation, we also analysed NGAL levels in pancreatic cancer cell lines with varying grades of differentiation. Although NGAL expression was strongly upregulated in pancreatic cancer, and moderately in pancreatitis, only a weak expression could be detected in the healthy pancreas. The average composite score for adenocarcinoma (4.26±2.44) was significantly higher than that for the normal pancreas (1.0) or pancreatitis (1.0) (P<0.0001). Further, although both well- and moderately differentiated pancreatic cancer were positive for NGAL, poorly differentiated adenocarcinoma was uniformly negative. Importantly, NGAL expression was detected as early as the PanIN-1 stage, suggesting that it could be a marker of the earliest premalignant changes in the pancreas. Further, we examined NGAL levels in serum samples. Serum NGAL levels were above the cutoff for healthy individuals in 94% of pancreatic cancer and 62.5% each of acute and chronic pancreatitis samples. However, the difference between NGAL levels in pancreatitis and pancreatic cancer was not significant. A ROC curve analysis revealed that ELISA for NGAL is fairly accurate in distinguishing pancreatic cancer

Improved sensitivity of vaginal self-collection and high-risk human papillomavirus testing.

PubMed

Belinson, Jerome L; Du, Hui; Yang, Bin; Wu, Ruifang; Belinson, Suzanne E; Qu, Xinfeng; Pretorius, Robert G; Yi, Xin; Castle, Philip E

2012-04-15

Self-collected vaginal specimens tested for high-risk human papillomavirus (HR-HPV) have been shown to be less sensitive for the detection of cervical intraepithelial neoplasia or cancer (≥CIN 3) than physician-collected endocervical specimens. To increase the sensitivity of self-collected specimens, we studied a self-sampling device designed to obtain a larger specimen from the upper vagina (POI/NIH self-sampler) and a more sensitive polymerase chain reaction (PCR)-based HR-HPV assay. Women (10,000) were screened with cervical cytology and HR-HPV testing of vaginal self-collected and endocervical physician-collected specimens. Women were randomly assigned to use either a novel self-collection device (POI/NIH self-sampler) or conical-shaped brush (Qiagen). The self-collected and clinician-collected specimens were assayed by Cervista (Hologic) and the research only PCR-based matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF). Women with any abnormal screening test underwent colposcopy and biopsy. Women (8,556), mean age of 38.9, had complete data; 1.6% had ≥ CIN 3. For either HR-HPV assay, the sensitivity was similar for the two self-collection devices. Tested with Cervista, the sensitivity for ≥CIN 3 of self-collected specimens was 70.9% and for endocervical specimens was 95.0% (p = 0.0001). Tested with MALDI-TOF, the sensitivity for ≥CIN 3 of self-collected specimens was 94.3% and for endocervical specimens was also 94.3% (p = 1.0). A self-collected sample using a PCR-based assay with the capability of very high throughput has similar sensitivity as a direct endocervical specimen obtained by a physician. Large population-based screening "events" in low-resource settings could be achieved by promoting self-collection and centralized high-throughput, low-cost testing by PCR-based MALDI-TOF. Copyright © 2011 UICC.

Cervical cytopathological changes among women with vaginal discharge attending teaching hospital.

PubMed

Salih, Magdi M; AlHag, Fatma Tage El Sir; Khalifa, Mohammed Ahmed; El Nabi, Abdulla H

2017-01-01

To find cytology changes among women attending obstetrics and gynaecology clinic with complaints of vaginal discharges. This descriptive hospital-based cytological study was conducted at the outpatient clinic of the obstetrics and gynaecology department. Two hundred women with complaints of vaginal discharge were selected. Their detailed histories were documented on a special request form. Pap smears were then obtained and sent for cytological examination to the cytopathology department. All low-grade squamous intraepithelial lesion (LSIL) cases were advised to follow-up with Pap smears in the next 6-12 months. Those with high-grade squamous intraepithelial lesion (HSIL) were further investigated by a cervical biopsy and managed accordingly. The statistical analysis was performed using, the Statistical Package for Social Science (SPSS). Chi-square and cross-tabulation were used in this study. The cytological examination of Pap smears showed no changes (i.e. negative findings) in 88 (44%) cases, while Candida species infection was the most prevalent, which was found in 67 (33.5%) of the cases. Bacterial vaginosis was found in 39 women (19.5%); 6 women (3%) were reported with dyskaryotic changes. Two cases were found to have LSIL and 4 women had HSIL. Infection is common among the illiterate group of women. Women with vaginal discharges should undergo screening tests for evaluation by cervical smear for the early detection of cervical precancer conditions. There is an urgent need to establish a screening program for cervical cancer in Sudan.

Stepwise radical endoscopic resection for eradication of Barrett's oesophagus with early neoplasia in a cohort of 169 patients.

PubMed

Pouw, Roos E; Seewald, Stefan; Gondrie, Joep J; Deprez, Pierre H; Piessevaux, Hubert; Pohl, Heiko; Rösch, Thomas; Soehendra, Nib; Bergman, Jacques J

2010-09-01

Endoscopic resection is safe and effective to remove early neoplasia (ie,high-grade intra-epithelial neoplasia/early cancer) in Barrett's oesophagus. To prevent metachronous lesions during follow-up, the remaining Barrett's oesophagus can be removed by stepwise radical endoscopic resection (SRER). The aim was to evaluate the combined experience in four tertiary referral centres with SRER to eradicate Barrett's oesophagus with early neoplasia. Retrospective cohort study. Four tertiary referral centres. 169 patients (151 males, age 64 years (IQR 57-71), Barrett's oesophagus 3 cm (IQR 2-5)) with early neoplasia in Barrett's oesophagus < or = 5 cm, without deep submucosal infiltration or lymph node metastases, treated by SRER between January 2000 and September 2006. Endoscopic resection every 4-8 weeks, until complete endoscopic and histological eradication of Barrett's oesophagus and neoplasia. According to intention-to-treat analysis complete eradication of all neoplasia and all intestinal metaplasia by the end of the treatment phase was reached in 97.6% (165/169) and 85.2% (144/169) of patients, respectively. One patient had progression of neoplasia during treatment and died of metastasised adenocarcinoma (0.6%). After median follow-up of 32 months (IQR 19-49), complete eradication of neoplasia and intestinal metaplasia was sustained in 95.3% (161/169) and 80.5% (136/169) of patients, respectively. Acute, severe complications occurred in 1.2% of patients, and 49.7% of patients developed symptomatic stenosis. SRER of Barrett's oesophagus < or = 5 cm containing early neoplasia appears to be an effective treatment modality with a low rate of recurrent lesions during follow-up. The procedure, however, is technically demanding and is associated with oesophageal stenosis in half of the patients.

Characterizing T-cell response in low-grade and high-grade vulval intraepithelial neoplasia, study of CD3, CD4 and CD8 expressions.

PubMed

Gul, Nahid; Ganesan, Raji; Luesley, David M

2004-07-01

The objective of our study was to compare immunocyte infiltrates in vulval epithelium from low-grade and high-grade vulval intraepithelial neoplasia (VIN) lesions to determine if difference in T-cell presence reflected the grade of VIN. Thirty-six vulval specimens were obtained from 24 patients who had previously undergone vulval biopsies for VIN, 14 high-grade diseases (VIN 3 with or without HPV) and 14 low-grade diseases (VIN 1 and VIN 2 with or without HPV). Eight samples of normal vulval tissue were selected from the excision margins of resected vulval biopsies. The lymphocyte surface markers included CD3 (Pan T-cell marker), CD4 (T helper cells), and CD8 (T cytotoxic cells). Each tissue section was visualized under high power magnification and cells were counted in 10 random areas at the dermo-epidermal junction. A significantly higher number of total mean T lymphocytes were detected in VIN specimens compared to normal vulval tissue (P = 0.002). In low-grade VIN, there were significantly more CD8 cells than CD4 when compared to high-grade VIN. This difference in CD4/CD8 ratio was significant (P = 0.001). This study suggests that increased CD8 response in VIN is a feature of low-grade disease and we speculate that this may be a protective mechanism. In high-grade disease, both CD4 cells and CD8 cells are equally present with preservation of normal CD4/CD8 ratio.

Final results of a phase 2 study using continuous 5% Imiquimod cream application in the primary treatment of high-grade vulva intraepithelial neoplasia.

PubMed

Le, Tien; Menard, Chantal; Hicks-Boucher, Wendy; Hopkins, Laura; Weberpals, Johanne; Fung-Kee-Fung, Michael

2007-09-01

To investigate the activity of 5% Imiquimod cream in the primary treatment of vulva intraepithelial neoplasia (VIN) grade 2/3. Patients with histologically confirmed VIN 2/3 were recruited from regional colposcopy units. A Simon two-stage phase 2 study design was used. Imiquimod cream was applied over the abnormal VIN areas by the patients, using an escalating dose regimen for a total treatment duration of 16 weeks. Colposcopy assessments were performed every 2 weeks to evaluate for response. A historical cohort of VIN 2/3 patients treated with primary surgical ablation was used to compare recurrence patterns. Thirty-nine patients enrolled in the study. Six patients dropped out due to side effects and non-compliance with study protocol. Thirty-six patients (92%) had VIN 3. Therapy was well tolerated with the most common observed side effects being only minor skin irritation at the application site. Histologic complete response was observed in 21 patients with partial response in another nine patients. The overall response rate was 77% using intention to treat principle. No VIN progression or cancer was diagnosed. At a median follow-up of 16 months in the whole study cohort, eight recurrences (20.5%) were observed. In comparison, the recurrence rate for primary surgically treated patients was 53.5% (p=0.013). Imiquimod cream was well tolerated and resulted in the regression in a majority of high-grade VIN lesions. The recurrence rate appeared to be comparable to primary surgical ablation.

Molecular evidence that invasive adenocarcinoma can mimic prostatic intraepithelial neoplasia (PIN) and intraductal carcinoma through retrograde glandular colonization.

PubMed

Haffner, Michael C; Weier, Christopher; Xu, Meng Meng; Vaghasia, Ajay; Gürel, Bora; Gümüşkaya, Berrak; Esopi, David M; Fedor, Helen; Tan, Hsueh-Li; Kulac, Ibrahim; Hicks, Jessica; Isaacs, William B; Lotan, Tamara L; Nelson, William G; Yegnasubramanian, Srinivasan; De Marzo, Angelo M

2016-01-01

Prostate cancer often manifests as morphologically distinct tumour foci and is frequently found adjacent to presumed precursor lesions such as high-grade prostatic intraepithelial neoplasia (HGPIN). While there is some evidence to suggest that these lesions can be related and exist on a pathological and morphological continuum, the precise clonal and temporal relationships between precursor lesions and invasive cancers within individual tumours remain undefined. Here, we used molecular genetic, cytogenetic, and histological analyses to delineate clonal, temporal, and spatial relationships between HGPIN and cancer lesions with distinct morphological and molecular features. First, while confirming the previous finding that a substantial fraction of HGPIN lesions associated with ERG-positive cancers share rearrangements and overexpression of ERG, we found that a significant subset of such HGPIN glands exhibit only partial positivity for ERG. This suggests that such ERG-positive HGPIN cells either rapidly invade to form adenocarcinoma or represent cancer cells that have partially invaded the ductal and acinar space in a retrograde manner. To clarify these possibilities, we used ERG expression status and TMPRSS2-ERG genomic breakpoints as markers of clonality, and PTEN deletion status to track temporal evolution of clonally related lesions. We confirmed that morphologically distinct HGPIN and nearby invasive cancer lesions are clonally related. Further, we found that a significant fraction of ERG-positive, PTEN-negative HGPIN and intraductal carcinoma (IDC-P) lesions are most likely clonally derived from adjacent PTEN-negative adenocarcinomas, indicating that such PTEN-negative HGPIN and IDC-P lesions arise from, rather than give rise to, the nearby invasive adenocarcinoma. These data suggest that invasive adenocarcinoma can morphologically mimic HGPIN through retrograde colonization of benign glands with cancer cells. Similar clonal relationships were also seen for

Coexisting High-grade Vulvar Intraepithelial Neoplasia (VIN) and Condyloma Acuminatum - Independent Lesions Due to Different HPV Types Occurring in Immunocompromised Patients

PubMed Central

Maniar, Kruti P.; Ronnett, Brigitte M.; Vang, Russell; Yemelyanova, Anna

2012-01-01

The majority of vulvar intraepithelial neoplasia (VIN) is high-grade and is related to high-risk human papillomavirus (HRHPV) (most commonly HPV16). It is considered to be the precursor of HRHPV-related vulvar squamous cell carcinoma. Vulvar condyloma acuminatum is low-risk HPV (LRHPV)-related (most commonly types 6 and 11) and has virtually no risk of neoplastic progression. While infection with multiple LR- and HRHPV types has been reported for cervical squamous intraepithelial lesions, coexisting vulvar condyloma and adjacent high-grade VIN have not been well characterized. Eleven cases of concurrent condyloma acuminatum and adjacent flat high-grade VIN and three cases of high-grade VIN with prominent condylomatous architecture were analyzed using immunohistochemical (IHC) analysis of p16 expression, in situ hybridization (ISH) for HPV detection (HPV6/11, HPV16, HPV 18, and HPV WS [types 6,11,16,18,31,33,35,45,51,52] probes), and HPV typing by PCR-based method (in select cases). All patients had underlying immunosuppressive conditions (human immunodeficiency virus infection or post-transplant therapy). Among the 11 cases of concurrent high-grade VIN and condyloma, the lesions were directly adjacent to one another in 5 cases (with 2 of these demonstrating an intimate admixture of lesions), and in 6 cases were found in separate tissue sections from the same specimen. Diffuse/strong p16 expression was seen in all high-grade VIN lesions, whereas patchy/weak staining was found in all condylomata. All condylomata contained HPV 6 or 11 as detected by ISH. All of the accompanying high-grade VIN lesions had HRHPV detected. Ten contained HPV 16 (9 by ISH, 1 by PCR), with the remaining case containing multiple HPV types by PCR. All condylomatous high-grade VIN lesions demonstrated diffuse/strong p16 expression and had evidence of HRHPV (one with HPV 16 by ISH, one with HPV 18 by ISH, and one with multiple HPV types by PCR), with no detection of HPV 6 or 11 by ISH. The

Clinical significance of serum anti-human papillomavirus 16 and 18 antibodies in cervical neoplasia.

PubMed

Chay, Doo Byung; Cho, Hanbyoul; Kim, Bo Wook; Kang, Eun Suk; Song, Eunseop; Kim, Jae-Hoon

2013-02-01

To estimate the clinical significance of serum anti-human papillomavirus (HPV) antibodies and high-risk cervical HPV DNA in cervical neoplasia. The study population comprised patients who were histopathologically diagnosed with cervical intraepithelial neoplasia (CIN) 1 (n=64), CIN 2 and 3 (n=241), cervical cancer (n=170), and normal control participants (n=975). Cervical HPV DNA tests were performed through nucleic acid hybridization assay tests, and serum anti-HPV 16 and 18 antibodies were measured by competitive immunoassay. The associations of HPV DNA and anti-HPV antibodies were evaluated with demographic characteristics and compared according to the levels of disease severity. Anti-HPV antibodies were also investigated with clinicopathologic parameters, including survival data. Among various demographic characteristics, factors involving sexual behavior had a higher tendency of HPV DNA positivity and HPV seropositivity. Human papillomavirus DNA mean titer and positivity were both increased in patients with cervical neoplasia compared with those with normal control participants, but there was no statistical difference among types of cervical neoplasia. Serum anti-HPV 16 antibodies were also able to differentiate cervical neoplasia from a normal control participant and furthermore distinguished CIN 1 from CIN 2 and 3 (odd ratio 2.87 [1.43-5.78], P=.002). In cervical cancer, HPV 16 seropositivity was associated with prolonged disease-free survival according to the univariable analysis (hazard ratio=0.12 [0.01-0.94], P=.044). Serum anti-HPV 16 antibodies can distinguish cervical neoplasia from a normal control and has the advantage of identifying high-grade CIN. Moreover, in cervical cancer, HPV 16 seropositivity may be associated with a more favorable prognosis. II.

Value-based medicine analysis on loop electrosurgical excision procedure and CO2 laser vaporization for the treatment of cervical intraepithelial neoplasia 2.

PubMed

Sun, Lu-lu; Cao, Dong-yan; Yang, Jia-xin; Bian, Mei-lu; Wei, Li-hui; Shen, Keng

2012-08-01

The best treatment option for cervical intraepithelial neoplasia 2 (CIN2) is controversial and there is a lack of studies in value-based medicine. This multicenter comparative study was undertaken to evaluate the effectiveness, cost-effectives and quality of life (QOL) of loop electrosurgical excision procedure (LEEP) and CO(2) laser vaporization for the treatment of CIN2. A database of LEEP and laser vaporizations performed at three research centers was created. Patients with colposcopic-histopathologically confirmed CIN2 were randomly submitted to LEEP and laser vaporization. Cytology, human papilloma virus (HPV) DNA test and histology were performed, and a questionnaire on QOL was filled out during follow-up. Effectiveness, cost-effectives and QOL were analyzed. Three hundred and thirty-eight women with CIN2 were included in the study. Frequencies of remission, and persistent and recurrent CIN were 89.2%, 7.2%, and 3.6% for LEEP, and 86.7%, 12.6%, 0.70% for laser, respectively. There was no significant difference in remission and persistence of CIN. There was a significant difference in the number of operations, recovery time and costs. Women treated with two methods showed relatively identical QOL. Both LEEP and CO(2) laser vaporization are effective and reliable treatments for CIN2, whereas cervical tissue can be obtained for histology by LEEP. Preoperative evaluation and postoperative follow-up are important. Gynecologists should pay attention to QOL of patients with CIN. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

High-risk human papillomavirus infection of the genital tract of women with a previous history or current high-grade vulvar intraepithelial neoplasia.

PubMed

Goffin, Frederic; Mayrand, Marie-Hélène; Gauthier, Philippe; Alobaid, A; Lussier, Christian; Provencher, Diane; Drouin, Pierre; Franco, Eduardo L; Coutlée, François

2006-06-01

Human papillomavirus (HPV) infection is associated with high-grade vulvar intraepithelial neoplasia (VIN-3). The prevalence of anogenital HPV infection in women with previously treated VIN-3 has not been documented yet. This cross-sectional study compared high-risk HPV DNA detection rates in women with past (n = 30) and current (n = 22) VIN-3 to those without current or past VIN (n = 86). HPV DNA was detected in vulvar and cervical samples with Hybrid Capture 2 (HC-2). Smoking was associated in multivariate analysis with current VIN-3 (odds ratio (OR) 8.3, 95% confidence interval (CI) 2.0-8.2) and any VIN-3 history (OR 6.5, 95% CI 2.5-16.5). High-risk HPV DNA was found on the vulva of 64%, 33%, and 20% of women with current VIN-3, past VIN-3, and without previous or current VIN, respectively. After controlling for age and smoking, high-risk HPV vulvar infection was associated with cervical high-risk HPV infection (OR 8.6, 95% CI 2.8-26.5; P = 0.001). After controlling for age, HPV infection was more often multifocal in women with current VIN-3 compared to women with previous but no current VIN-3 lesion (OR 17.6, 95% CI 1.4-227.2). Multifocal vulvar HPV infection was detected in women with previous or active VIN-3. Longitudinal studies are required to determine if the multifocality of HPV infection on the vulva could explain the high recurrence rate of VIN-3.

Risks of cervical intraepithelial neoplasia grade 3 or invasive cancers in ASCUS women with different management: a population-based cohort study.

PubMed

Tai, Yi Jou; Chen, Yun Yuan; Hsu, Huang Cheng; Chiang, Chun Ju; You, San Lin; Chen, Chi An; Cheng, Wen Fang

2018-07-01

To investigate the progression risk of atypical squamous cells of undetermined significance (ASCUS) with different clinical managements. Women with their first diagnosis of ASCUS cytology were retrieved from the national cervical cancer screening database and linked to the national health insurance research database to identify the management of these women. The incidences of developing cervical intraepithelial neoplasia grade 3 and invasive cervical cancer (CIN3+) were calculated, and the hazard ratios (HRs) were estimated using a Cox proportional hazards model. This study was approved by the Research Ethics Committee of the National Taiwan University Hospital and is registered at ClinicalTrials.gov (Identifier: NCT02063152). There were total 69,741 women included. Various management strategies including colposcopy, cervical biopsies and/or endocervical curettage, and cryotherapy, failed to reduce the risk of subsequent CIN3+ compared with repeat cervical smears. Loop electrosurgical excision procedure/conization significantly decreased risk of subsequent CIN3+ lesions (HR=0.22; 95% confidence interval [CI]=0.07-0.68; p=0.010). Women in their 40s-50s had an approximately 30% risk reduction compared to other age groups. Women with a previous screening history >5 years from the present ASCUS diagnosis were at increased risk for CIN3+ (HR=1.24; 95% CI=1.03-1.49; p=0.020). In women of first-time ASCUS cytology, a program of repeat cytology can be an acceptable clinical option in low-resource settings. Caution should be taken especially in women with remote cervical screening history more than 5 years. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

Low Prostate Concentration of Lycopene Is Associated with Development of Prostate Cancer in Patients with High-Grade Prostatic Intraepithelial Neoplasia

PubMed Central

Mariani, Simone; Lionetto, Luana; Cavallari, Michele; Tubaro, Andrea; Rasio, Debora; De Nunzio, Cosimo; Hong, Gena M.; Borro, Marina; Simmaco, Maurizio

2014-01-01

Prostate cancer (PC) is a frequent male malignancy and represents the second most diagnosed cancer in men. Since pre-cancerous lesions, i.e., the high-grade prostatic intraepithelial neoplasia (HGPIN), can be detected years before progression to PC, early diagnosis and chemoprevention are targeted strategies to reduce PC rates. Animal studies have shown that lycopene, a carotenoid contained in tomatoes, is a promising candidate for the chemoprevention of PC. However, its efficacy in humans remains controversial. The present study aimed to investigate the relevance of plasma and prostate concentration of lycopene after a lycopene-enriched diet in patients diagnosed with HGPIN. Thirty-two patients diagnosed with HGPIN were administered a lycopene-enriched diet (20–25 mg/day of lycopene; through 30 g/day of triple concentrated tomato paste) for 6 months. A 6-month follow-up prostate biopsy assessed progression to PC. Patients were classified into three groups according to the histopathological features of the 6-month follow-up biopsy results: prostatitis; HGPIN and PC. PSA and plasma lycopene levels were measured before and after the dietary lycopene supplementation. Prostatic lycopene concentration was only assessed after the supplementation diet. Only prostatic lycopene concentration showed significant differences between the three groups (p = 0.03). Prostatic lycopene concentration below a 1 ng/mg threshold was associated with PC at 6-month follow-up biopsy (p = 0.003). We observed no overall benefits from a 6-month lycopene supplementation, as the rate of HGPIN progression to PC in our population (9/32, 28%) was similar to rates reported in the literature. Baseline PSA levels also showed no significant changes after a lycopene-enriched diet. Our findings point to prostatic lycopene concentration as a promising biomarker of PC. Further prospective longitudinal studies are needed to assess the prognostic role of prostatic lycopene in PC. PMID:24451130

Role of active and passive smoking in high-risk human papillomavirus infection and cervical intraepithelial neoplasia grade 2 or worse.

PubMed

Feng, Rui Mei; Hu, Shang Ying; Zhao, Fang Hui; Zhang, Rong; Zhang, Xun; Wallach, Asya Izraelit; Qiao, You Lin

2017-09-01

We performed a pooled analysis to examine cigarette smoking and household passive smoke exposure in relation to the risk of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia grade 2+ (CIN2+). Data were pooled from 12 cross-sectional studies for cervical cancer screenings from 10 provinces of China in 1999-2007. A total of 16,422 women were analyzed, along with 2,392 high-risk-HPV (hr-HPV) positive women and 381 CIN2+ cases. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models controlling for sexual and non-sexual confounding factors. There was an excess risk between active smoking and hr-HPV infection and CIN2+. Adjusted OR for ever smokers vs. never smokers was 1.45 (95% CI=1.10-1.91), for hr-HPV infection and 1.89 (95% CI=1.03-3.44), for CIN2+. Passive smoking had a slightly increased risk on the hr-HPV infection with adjusted OR 1.11 (1.00-1.24), but no statistical association was observed between passive smoke exposure and CIN2+. Compared with the neither active nor passive smokers, both active and passive smokers had a 1.57-fold (95% CI=1.14-2.15) increased risk of HPV infection and a 1.99-fold (95% CI=1.02-3.88) risk of CIN2+. Our large multi-center cross-sectional study found active smoking could increase the risk of overall hr-HPV infection and CIN2+ adjusted by passive smoking and other factors. Passive smoking mildly increased the risk of HPV infection but not the CIN2+. An interaction existed between passive tobacco exposure and active smoking for hr-HPV infection and the CIN2+. Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology

Piecemeal Versus En Bloc Resection of Large Rectal Adenomas

ClinicalTrials.gov

2018-06-04

Colorectal Adenoma With Mild Dysplasia; Colorectal Adenoma With Severe Dysplasia; Colorectal Adenomatous Polyp; Colorectal Low Grade Intraepithelial Neoplasia; Colorectal High Grade Intraepithelial Neoplasia

Evaluation of candidate methylation markers to detect cervical neoplasia.

PubMed

Shivapurkar, Narayan; Sherman, Mark E; Stastny, Victor; Echebiri, Chinyere; Rader, Janet S; Nayar, Ritu; Bonfiglio, Thomas A; Gazdar, Adi F; Wang, Sophia S

2007-12-01

Studies of cervical cancer and its immediate precursor, cervical intraepithelial neoplasia 3 (CIN3), have identified genes that often show aberrant DNA methylation and therefore represent candidate early detection markers. We used quantitative PCR assays to evaluate methylation in five candidate genes (TNFRSF10C, DAPK1, SOCS3, HS3ST2 and CDH1) previously demonstrated as methylated in cervical cancer. In this analysis, we performed methylation assays for the five candidate genes in 45 invasive cervical cancers, 12 histologically normal cervical specimens, and 23 liquid-based cervical cytology specimens confirmed by expert review as unequivocal demonstrating cytologic high-grade squamous intraepithelial lesions, thus representing the counterparts of histologic CIN3. We found hypermethylation of HS3ST2 in 93% of cancer tissues and 70% of cytology specimens interpreted as CIN3; hypermethylation of CDH1 was found in 89% of cancers and 26% of CIN3 cytology specimens. Methylation of either HS3ST2 or CDH1 was observed in 100% of cervical cancer tissues and 83% of CIN3 cytology specimens. None of the five genes showed detectable methylation in normal cervical tissues. Our data support further evaluation of HS3ST2 and CDH1 methylation as potential markers of cervical cancer and its precursor lesions.

A trial of radiofrequency ablation for anal intraepithelial neoplasia.

PubMed

Goldstone, Robert N; Hasan, Shirin R; Drury, Steven; Darragh, Teresa M; van Zante, Annemieke; Goldstone, Stephen E

2017-03-01

Radiofrequency ablation (RFA) effectively treats esophageal high-grade dysplasia, but its efficacy in treating anal canal high-grade squamous intraepithelial lesions (HSILs) is unsubstantiated. This prospective study assessed the safety and efficacy of applying hemi-circumferential RFA to anal canal HSIL. Twenty-one HIV-negative participants with HSIL occupying ≤ half the anal canal circumference were treated with hemi-circumferential anal canal RFA. Participants were assessed every 3 months for 12 months with high-resolution anoscopy; recurrence in the treatment zone was re-treated with focal RFA. Twenty-one participants with a mean of 1.7 lesions (range 1-4) enrolled and completed the trial. Six (29 %) participants had recurrent HSIL within the treated hemi-circumference within 1 year. Four participants (19 %) had persistence of an index lesion at 3 months. One (2.9 %) index HSIL persisted again at 12 months. No participants had more than two RFA treatments. KM curve-predicted HSIL-free survival within the treatment zone at 1 year was 76 % (95 % CI 52-89 %). Comparing the first 7 and last 14 participants, the predicted 1-year HSIL-free survivals are 43 % (95 % CI 10-73 %) and 93 % (95 % CI 59-99 %), respectively (p = 0.008), suggesting a learning curve with the treating physician. Multivariable analysis showed decreased recurrence in the last 14 participants (HR 0.02; 95 % CI 0.001-0.63) while increasing BMI increased recurrence (HR 1.43, 95 % CI 1.01-2.01). No participants had device or procedure-related serious adverse events, anal stricture, or heavy bleeding. Hemi-circumferential RFA yielded a high rate of anal HSIL eradication in HIV-negative patients at 1 year with minimal adverse events. Lesion persistence was probably related to incomplete initial ablation.

Differentially expressed proteins among normal cervix, cervical intraepithelial neoplasia and cervical squamous cell carcinoma.

PubMed

Zhao, Q; He, Y; Wang, X-L; Zhang, Y-X; Wu, Y-M

2015-08-01

To explore the differentially expressed proteins in normal cervix, cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) tissues by differential proteomics technique. Cervical tissues (including normal cervix, CIN and CSCC) were collected in Department of Gynecologic Oncology of Beijing Obstetrics and Gynecology Hospital. Two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) and DeCyder software were used to detect the differentially expressed proteins. Matrix-assisted laser desorption/ionization-time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) was used to identify the differentially expressed proteins. Western blot (WB) and immunohistochemistry (IHC) were performed to validate the expressions of selected proteins among normal cervix, CIN and CSCC. 2-D DIGE images with high resolution and good repeatability were obtained. Forty-six differentially expressed proteins (27 up-regulated and 19 down-regulated) were differentially expressed among the normal cervix, CIN and CSCC. 26 proteins were successfully identified by MALDI-TOF/TOF MS. S100A9 (S100 calcium-binding protein A9) was the most significantly up-regulated protein. Eukaryotic elongation factor 1-alpha-1 (eEF1A1) was the most significantly down-regulated protein. Pyruvate kinase isozymes M2 (PKM2) was both up-regulated and down-regulated. The results of WB showed that with the increase in the severity of cervical lesions, the expression of S100A9 protein was significantly increased among the three groups (P = 0.010). The expression of eEF1A1 was reduced but without significant difference (P = 0.861). The expression of PKM2 was significantly reduced (P = 0.000). IHC showed that protein S100A9 was mainly expressed in the cytoplasm, and its positive expression rate was 20.0 % in normal cervix, 70.0 % in CIN and 100.0 % in CSCC, with a significant difference among them (P = 0.006). eEF1A1 was mainly expressed in the cell plasma, and its

Antioxidant enzyme expression and reactive oxygen species damage in prostatic intraepithelial neoplasia and cancer.

PubMed

Bostwick, D G; Alexander, E E; Singh, R; Shan, A; Qian, J; Santella, R M; Oberley, L W; Yan, T; Zhong, W; Jiang, X; Oberley, T D

2000-07-01

Oxidative stress results in damage to cellular structures and has been linked to many diseases, including cancer. The authors sought to determine whether the expression of three major antioxidant enzymes, copper-zinc superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), and catalase, was altered in human prostate carcinoma and its likely precursor, high grade prostatic intraepithelial neoplasia (PIN). The level of reactive oxygen species damage was evaluated by measuring the expression of the DNA adduct 8-hydroxydeoxyguanosine. The authors evaluated the tissue expression of the antioxidant enzymes in prostate carcinoma by immunohistochemistry, immunogold electron microscopy, and enzymatic assay. The polymerase chain reaction was used to amplify and screen tissue specimens for the genes of SOD1, SOD2, and extracellular SOD (SOD3). Matched paraffin embedded tissue sections were evaluated by RNA in situ hybridization for expression of SOD1 and immunohistochemically for the DNA adduct 8-hydroxydeoxyguanosine. All prostatic tissues, including cancer, displayed immunoreactivity for the three antioxidant enzymes in epithelial cells, with no staining of the stroma, inflammatory cells, or endothelial cells. The number of immunoreactive cells was greater in benign epithelium than in PIN and cancer for each enzyme. The mean percentage and intensity of immunoreactive cells was greatest for SOD2, intermediate for SOD1, and lower for catalase. Staining in cancer was heterogeneous. Immunogold ultrasound studies revealed strong mitochondrial labeling for SOD2, which was greater in benign epithelium than in cancer; SOD1 labeling was invariably weaker, with nuclear labeling in benign epithelium and cytoplasmic labeling in cancer cells. There was no difference in enzyme activity for the three antioxidant enzymes between benign epithelium and cancer. No mutations were found in the 5 exons of SOD1, 5 exons of SOD2, and 3 exons of SOD3, except for 3 of 20 cases with

Bacterial vaginosis, aerobic vaginitis, vaginal inflammation and major Pap smear abnormalities.

PubMed

Vieira-Baptista, P; Lima-Silva, J; Pinto, C; Saldanha, C; Beires, J; Martinez-de-Oliveira, J; Donders, G

2016-04-01

The purpose of this investigation was to evaluate the impact of the vaginal milieu on the presence of abnormal Pap smears and a positive human papilloma virus (HPV) test. A cross-sectional study was conducted between June 2014 and May 2015, evaluating the vaginal discharge by fresh wet mount microscopy and comparing these data with Pap smear findings. Wet mount slides were scored for bacterial vaginosis (BV), aerobic vaginitis (AV), presence of Candida and Trichomonas vaginalis. Cytologic evaluation was done on all Pap smears according to the Bethesda criteria. The cobas© HPV Test (Roche) was performed for HPV detection. A total of 622 cases were evaluated. The mean age of the patients was 41.6 ± 10.65 years (range 21-75). Eighty-three women (13.3 %) had a cytology result worse than low-grade squamous intraepithelial lesion (LSIL). When comparing this group with the one with normal or minor [atypical squamous cells of undetermined significance (ASC-US) or LSIL] Pap smear abnormalities, there were no differences in the presence of Candida (32.5 % vs. 33.2 %, p = 1.0), absence of lactobacilli (38.6 % vs. 32.5 %, p = 0.32) or BV (20.5 % vs. 13.2 %, p = 0.09). On the other hand, moderate or severe inflammation (msI) (41.0 % vs. 28.8 %, p = 0,04), moderate or severe AV (msAV) (16.9 % vs. 7.2 %, p = 0.009) and msAV/BV (37.3 % vs. 20.0 %, p = 0.001) were more common in women with such major cervical abnormalities. No significant association was found between deviations of the vaginal milieu and high-risk HPV infection. The presence of msI or msAV, but not BV, is independently associated with an increased risk of major cervical cytological abnormalities, but not with HPV infection.

GLUT-1 Expression in Pancreatic Neoplasia

PubMed Central

Basturk, Olca; Singh, Rajendra; Kaygusuz, Ecmel; Balci, Serdar; Dursun, Nevra; Culhaci, Nil; Adsay, N. Volkan

2011-01-01

Objectives GLUT-1 has been found to have an important role in the upregulation of various cellular pathways and implicated in neoplastic transformation correlating with biological behavior in malignancies. However, literature regarding the significance of GLUT-1 expression in pancreatic neoplasia has been limited and controversial. Methods Immunohistochemical expression of GLUT-1 was tested in a variety of pancreatic neoplasia including ductal adenocarcinomas (DAs), pancreatic intraepithelial neoplasms (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and serous cystadenomas. Results There was a progressive increase in the expression of GLUT-1 from low- to higher-grade dysplastic lesions: All higher-grade PanINs/IPMNs (the ones with moderate/high-grade dysplasia) revealed noticeable GLUT-1 expression. Among the 94 DAs analyzed, there were minimal/moderate expression in 46 and significant expression in 24 DAs. However, all 4 clear-cell variants of DAs revealed significant GLUT-1 immunolabeling, as did areas of clear-cell change seen in other DAs. Moreover, all 12 serous cystadenomas expressed significant GLUT-1. GLUT-1 expression was also directly correlated with DA histological grade (P = 0.016) and tumor size (P = 0.03). Conclusions GLUT-1 may give rise to the distinctive clear-cell appearance of these tumors by inducing the accumulation of glycogen in the cytoplasm. Additionally, because GLUT-1 expression was related to histological grade and tumor size of DA, further studies are warranted to investigate the association of GLUT-1 with prognosis and tumor progression. PMID:21206329

High-risk human papillomavirus (hrHPV) E6/E7 mRNA testing by PreTect HPV-Proofer for detection of cervical high-grade intraepithelial neoplasia and cancer among hrHPV DNA-positive women with normal cytology.

PubMed

Rijkaart, D C; Heideman, D A M; Coupe, V M H; Brink, A A T P; Verheijen, R H M; Skomedal, H; Karlsen, F; Morland, E; Snijders, P J F; Meijer, C J L M

2012-07-01

Our aim was to investigate whether high-risk HPV (hrHPV) mRNA detection by PreTect HPV-Proofer can be used to stratify hrHPV DNA-positive women of different cytology classes for risk of high-grade cervical intraepithelial neoplasia or worse (cervical precancer or cancer, i.e., cervical intraepithelial neoplasia grade 2 or higher [≥ CIN2]). A total of 375 women participating in population-based screening, with a GP5+/6+-PCR hrHPV DNA-positive cervical scrape with normal cytology (n = 202), borderline or mild dyskaryosis (BMD) (n = 88), or moderate dyskaryosis or worse (>BMD) (n = 85), were enrolled. Cervical scrapes were additionally subjected to HPV16/18/31/33/45 E6/E7 mRNA analysis by PreTect HPV-Proofer (mRNA test). Referral and follow-up policies were based on cytology, hrHPV DNA, and mRNA testing. The primary study endpoint was the number of ≥CIN2 detected within 3 years of follow-up. The mRNA positivity increased with the severity of cytological abnormality, ranging from 32% (64/202) in hrHPV DNA-positive women with normal cytology to 47% (41/88) in BMD and 68% (58/85) in >BMD groups (P < 0.01). Women with ≥ CIN2 were more likely to test positive by mRNA test (63%) than women without evidence of ≥ CIN2 (32%; P < 0.01). A positive mRNA test result conferred an increased ≥ CIN2 risk in hrHPV DNA-positive women with normal cytology, i.e., 0.55 (95% confidence interval [95% CI], 0.34 to 0.76) in mRNA-positive versus 0.20 (95% CI, 0.07 to 0.33) in mRNA-negative women. In hrHPV DNA-positive women with BMD or >BMD, the result of the mRNA test did not influence the ≥ CIN2 risk. In conclusion, mRNA testing by PreTect HPV-Proofer might be of value to select hrHPV DNA-positive women with normal cytology in need of immediate referral for colposcopy.

High-Risk Human Papillomavirus (hrHPV) E6/E7 mRNA Testing by PreTect HPV-Proofer for Detection of Cervical High-Grade Intraepithelial Neoplasia and Cancer among hrHPV DNA-Positive Women with Normal Cytology

PubMed Central

Rijkaart, D. C.; Heideman, D. A. M.; Coupe, V. M. H.; Brink, A. A. T. P.; Verheijen, R. H. M.; Skomedal, H.; Karlsen, F.; Morland, E.; Snijders, P. J. F.

2012-01-01

Our aim was to investigate whether high-risk HPV (hrHPV) mRNA detection by PreTect HPV-Proofer can be used to stratify hrHPV DNA-positive women of different cytology classes for risk of high-grade cervical intraepithelial neoplasia or worse (cervical precancer or cancer, i.e., cervical intraepithelial neoplasia grade 2 or higher [≥CIN2]). A total of 375 women participating in population-based screening, with a GP5+/6+-PCR hrHPV DNA-positive cervical scrape with normal cytology (n = 202), borderline or mild dyskaryosis (BMD) (n = 88), or moderate dyskaryosis or worse (>BMD) (n = 85), were enrolled. Cervical scrapes were additionally subjected to HPV16/18/31/33/45 E6/E7 mRNA analysis by PreTect HPV-Proofer (mRNA test). Referral and follow-up policies were based on cytology, hrHPV DNA, and mRNA testing. The primary study endpoint was the number of ≥CIN2 detected within 3 years of follow-up. The mRNA positivity increased with the severity of cytological abnormality, ranging from 32% (64/202) in hrHPV DNA-positive women with normal cytology to 47% (41/88) in BMD and 68% (58/85) in >BMD groups (P < 0.01). Women with ≥CIN2 were more likely to test positive by mRNA test (63%) than women without evidence of ≥CIN2 (32%; P < 0.01). A positive mRNA test result conferred an increased ≥CIN2 risk in hrHPV DNA-positive women with normal cytology, i.e., 0.55 (95% confidence interval [95% CI], 0.34 to 0.76) in mRNA-positive versus 0.20 (95% CI, 0.07 to 0.33) in mRNA-negative women. In hrHPV DNA-positive women with BMD or >BMD, the result of the mRNA test did not influence the ≥CIN2 risk. In conclusion, mRNA testing by PreTect HPV-Proofer might be of value to select hrHPV DNA-positive women with normal cytology in need of immediate referral for colposcopy. PMID:22553244

Threshold cost-effectiveness analysis for a therapeutic vaccine against HPV-16/18-positive cervical intraepithelial neoplasia in the Netherlands.

PubMed

Luttjeboer, Jos; Setiawan, Didik; Cao, Qi; Cahh Daemen, Toos; Postma, Maarten J

2016-12-07

In this study, the potential price for a therapeutic vaccine against Human Papilloma Virus (HPV)-16 & 18 (pre)-malignant cervical lesions is examined. A decision tree model was built in the context of the new Dutch cervical cancer-screening program and includes a primary test for the presence of HPV. Based on data of cervical cancer screening and HPV prevalence in the Netherlands, cohorts were created with HPV-16 or 18 positive women with cervical intraepithelial neoplasia (CIN) 2 or 3 or cervical cancer stage 1A (FIGO 1A). In the base case, the vaccine price was based on equal numbers of effective treatments in the vaccine branch and the current treatments branch of the model, and parity in cost, i.e. total cost in both branches are the same. The vaccine price is calculated by subtracting the cost of the vaccine branch from cost in the standard treatment branch and divided by the total number of women in the cohort, thereby equalizing costs in both strategies. Scenario analyses were performed taking quality adjusted life years (QALYs) into account with €20,000/QALY, €50,000/QALY and €80,000/QALY as corresponding thresholds. Sensitivity analyses were specifically targeted at the characteristics of the type-specific HPV test in the screening practice and vaccine efficacy. A probabilistic sensitivity analysis (PSA) was performed to quantify the level of uncertainty of the results found in the base case. In the base case, break-even vaccine prices of €381, €568 and €1697 were found for CIN 2, CIN 3 and FIGO 1A, respectively. The PSA showed vaccine pricing below €310, €490 and €1660 will be cost saving with a likelihood of 95% for CIN 2, CIN 3 and FIGO 1A, respectively. The vaccine price proved to be very sensitive for inclusion of QALY gains, including the HPV-type specific test into the Dutch screening practice and vaccine efficacy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genetic analyses of isolated high-grade pancreatic intraepithelial neoplasia (HG-PanIN) reveal paucity of alterations in TP53 and SMAD4.

PubMed

Hosoda, Waki; Chianchiano, Peter; Griffin, James F; Pittman, Meredith E; Brosens, Lodewijk Aa; Noë, Michaël; Yu, Jun; Shindo, Koji; Suenaga, Masaya; Rezaee, Neda; Yonescu, Raluca; Ning, Yi; Albores-Saavedra, Jorge; Yoshizawa, Naohiko; Harada, Kenichi; Yoshizawa, Akihiko; Hanada, Keiji; Yonehara, Shuji; Shimizu, Michio; Uehara, Takeshi; Samra, Jaswinder S; Gill, Anthony J; Wolfgang, Christopher L; Goggins, Michael G; Hruban, Ralph H; Wood, Laura D

2017-05-01

High-grade pancreatic intraepithelial neoplasia (HG-PanIN) is the major precursor of pancreatic ductal adenocarcinoma (PDAC) and is an ideal target for early detection. To characterize pure HG-PanIN, we analysed 23 isolated HG-PanIN lesions occurring in the absence of PDAC. Whole-exome sequencing of five of these HG-PanIN lesions revealed a median of 33 somatic mutations per lesion, with a total of 318 mutated genes. Targeted next-generation sequencing of 17 HG-PanIN lesions identified KRAS mutations in 94% of the lesions. CDKN2A alterations occurred in six HG-PanIN lesions, and RNF43 alterations in five. Mutations in TP53, GNAS, ARID1A, PIK3CA, and TGFBR2 were limited to one or two HG-PanINs. No non-synonymous mutations in SMAD4 were detected. Immunohistochemistry for p53 and SMAD4 proteins in 18 HG-PanINs confirmed the paucity of alterations in these genes, with aberrant p53 labelling noted only in three lesions, two of which were found to be wild type in sequencing analyses. Sixteen adjacent LG-PanIN lesions from ten patients were also sequenced using targeted sequencing. LG-PanIN harboured KRAS mutations in 94% of the lesions; mutations in CDKN2A, TP53, and SMAD4 were not identified. These results suggest that inactivation of TP53 and SMAD4 are late genetic alterations, predominantly occurring in invasive PDAC. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Serial measurement of type-specific human papillomavirus load enables classification of cervical intraepithelial neoplasia lesions according to occurring human papillomavirus-induced pathway.

PubMed

Verhelst, Stefanie; Poppe, Willy A J; Bogers, Johannes J; Depuydt, Christophe E

2017-03-01

This retrospective study examined whether human papillomavirus (HPV) type-specific viral load changes measured in two or three serial cervical smears are predictive for the natural evolution of HPV infections and correlate with histological grades of cervical intraepithelial neoplasia (CIN), allowing triage of HPV-positive women. A cervical histology database was used to select consecutive women with biopsy-proven CIN in 2012 who had at least two liquid-based cytology samples before the diagnosis of CIN. Before performing cytology, 18 different quantitative PCRs allowed HPV type-specific viral load measurement. Changes in HPV-specific load between measurements were assessed by linear regression, with calculation of coefficient of determination (R) and slope. All infections could be classified into one of five categories: (i) clonal progressing process (R≥0.85; positive slope), (ii) simultaneously occurring clonal progressive and transient infection, (iii) clonal regressing process (R≥0.85; negative slope), (iv) serial transient infection with latency [R<0.85; slopes (two points) between 0.0010 and -0.0010 HPV copies/cell/day], and (v) transient productive infection (R<0.85; slope: ±0.0099 HPV copies/cell/day). Three hundred and seven women with CIN were included; 124 had single-type infections and 183 had multiple HPV types. Only with three consecutive measurements could a clonal process be identified in all CIN3 cases. We could clearly demonstrate clonal regressing lesions with a persistent linear decrease in viral load (R≥0.85; -0.003 HPV copies/cell/day) in all CIN categories. Type-specific viral load increase/decrease in three consecutive measurements enabled classification of CIN lesions in clonal HPV-driven transformation (progression/regression) and nonclonal virion-productive (serial transient/transient) processes.

Frequencies and role of regulatory T cells in patients with (pre)malignant cervical neoplasia

PubMed Central

Visser, J; Nijman, H W; Hoogenboom, B-N; Jager, P; van Baarle, D; Schuuring, E; Abdulahad, W; Miedema, F; van der Zee, A G; Daemen, T

2007-01-01

Oncogenic human papillomavirus (HPV)-infection is crucial for developing cervical cancer and its precursor lesions [cervical intraepithelial neoplasia (CIN)]. Regulatory T cells (Tregs) might be involved in the failure of the immune system to control the development of HPV-induced cancer. We investigated frequencies, phenotype and activity of Tregs in patients with cervical neoplasia. CIN and cervical cancer patients showed increased CD4+/CD25high T cell frequencies in peripheral blood and CD4+ T cell fraction. These CD4+/CD25high T cells represent Tregs as demonstrated by their low proliferation rate, low interferon (IFN)-γ/interleukin (IL)-10 ratio, high expression of CD45RO, GITR, CTLA-4, forkhead box P3 (FoxP3) and low CD45RA expression. Moreover, in HPV16+ cervical cancer patients, in-vitro depletion of CD25+ T cells resulted in increased IFN-γ T cell responses against HPV16 E6- and E7 peptides. Thus, increased frequencies of Tregs in cervical cancer patients may indeed suppress HPV-specific immunity. Longitudinal analysis of CD4+/CD25high T cell frequencies in patients showed a modest decline 1 year after curative surgery or chemoradiation. This study demonstrates increased frequencies and suppressive activity of Tregs in cervical cancer. These results imply that Tregs may suppress the immune control of cervical neoplasia and furthermore that suppression of immunity by Tregs will be another hurdle to overcome in therapeutic immunization strategies against cervical neoplasia. PMID:17937675

Accumulation of invariant NKT cells with increased IFN-γ production in persistent high-risk HPV-infected high-grade cervical intraepithelial neoplasia.

PubMed

Hu, Ting; Yang, Pei; Zhu, Hongmei; Chen, Xinlian; Xie, Xiaoyan; Yang, Mei; Liu, Shanling; Wang, He

2015-04-02

Persistent high-risk human papillomavirus (HR-HPV) infection has been implicated in the development of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer. Invariant natural killer T (iNKT) cells produce large amounts of cytokines to regulate immune responses. However, the role of iNKT cells in human persistent HPV-infected cervical tissues is unknown. In our study, 201 patients with diagnoses ranging from normal ectocervical tissue to CINIII from June 2010 to May 2012 were enrolled. HPV DNA and HPV types were detected using the hybrid capture-2 HPV DNA test. Flow cytometry was used to investigate iNKT and CD3+ T cell infiltration into cervical tissues. Real-time quantitative reverse transcription-polymerase chain reaction was used to study IFN-γ expression and immunohistochemistry was used to determine CD3+ T cell distribution. A significant increase in iNKT cells was observed in HPV-positive cervical tissues (p < 0.05), especially in CINII-III (p < 0.01). IFN-γ expression was also increased in HPV-positive cervical tissues (p < 0.05). CD3+ T cells were detected among both epithelium and stromal layers in cervical tissues, and the percentage of CD3+ T cells in HPV-positive cervical tissues was similar to that in HPV-negative cervical tissues (p > 0.05). The iNKT cell aggregation in cervical tissues during the progression from HPV infection to CIN indicates that iNKT cells might play an important role in suppressing immunity. IFN-γ expression could also be related to the HPV infection status. Preventing the accumulation or functioning of iNKT cells in cervical tissues may be a viable method to prevent the development of CIN. The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2521874671514142.

The Importance of High-Risk Human Papillomavirus Types Other Than 16 and 18 in Cervical Neoplasia.

PubMed

Robadi, Ibrahim A; Pharaon, Majed; Ducatman, Barbara S

2018-06-01

- Types 16 and 18 are the most widely studied high-risk types of human papillomavirus (HPV). However, other high-risk HPV types (HPV non-16/18) also play a significant role in cervical neoplasia. Currently, screening and management algorithms separate out HPV 16/18 from all other HPV non-16/18 types. In addition, most of the previously vaccinated population has only been vaccinated for these high-risk types, so many women are still vulnerable to HPV non-16/18 infections. - To review the prevalence and role of HPV non-16/18 neoplasia and to review current surveillance, management, and vaccination strategies in view of these findings. - The study comprised a review of the literature. - Although HPV non-16/18 types are less frequently associated with cervical intraepithelial neoplasia and cancer, they are nonetheless a significant cause of disease. Further stratification of higher-risk HPV non-16/18 may be necessary to improve prevention and management, however, regional prevalence differences may make a unified approach difficult. As HPV 16/18 infections decrease owing to vaccination of at-risk women, the relative frequency of HPV non-16/18 will increase, although the latest vaccine covers several more high-risk types.

HIV, human papillomavirus, and cervical neoplasia and cancer in the era of highly active antiretroviral therapy.

PubMed

De Vuyst, Hugo; Lillo, Flavia; Broutet, Nathalie; Smith, Jennifer S

2008-11-01

The objective of this study was to review the literature on the epidemiological association between human papillomavirus (HPV), HIV, and cervical neoplasia, and the impact of highly active antiretroviral therapy (HAART) on this association. MEDLINE was searched using the terms 'human papillomavirus', 'HPV', 'HIV', 'cervix', 'neoplasm', and 'antiretroviral' to identify articles published before December 2006. HIV-infection was strongly associated with a higher prevalence, incidence, and persistence of HPV infection and correlated with prevalence, incidence, persistence, and progression of squamous intraepithelial lesions. The association between HIV and invasive cervical carcinoma has been more difficult to establish, but is now fully recognized. HAART seems to have little, if any, beneficial effect on the natural history of intraepithelial lesions in HIV-positive women. Despite this fact, HAART, does increase the life expectancy of HIV-positive women. Therefore, it remains important to closely monitor HPV-related disease in women with HIV who are receiving HAART, particularly in regions of the world where cervical screening is not available routinely.

Home-Based or Clinic-Based Human Papillomavirus (HPV) Screening

ClinicalTrials.gov

2018-04-16

Atypical Squamous Cell of Undetermined Significance; Cervical Carcinoma; Cervical Intraepithelial Neoplasia Grade 2/3; Health Status Unknown; Human Papillomavirus Infection; Low Grade Cervical Squamous Intraepithelial Neoplasia; Stage 0 Cervical Cancer

Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance.

PubMed

Shi, Yong-Hua; Wang, Bo-Wei; Tuokan, Talaf; Li, Qiao-Zhi; Zhang, Ya-Jing

2015-01-01

A micronucleus is an additional small nucleus formed due to chromosomes or chromosomal fragments fail to be incorporated into the nucleus during cell division. In this study, we assessed the utility of micronucleus counting as a screening tool in cervical precancerous lesions in Thinprep cytological test smears under oil immersion. High risk HPV was also detected by hybrid capture-2 in Thinprep cytological test smears. Our results showed that micronucleus counting was significantly higher in high-grade squamous intraepithelial lesion (HSIL) and invasive carcinoma cases compared to low-grade squamous intraepithelial lesion (LSIL) and non-neoplastic cases. Receiver operating characteristic (ROC) curve analysis revealed that micronucleus counting possessed a high degree of sensitivity and specificity for identifying HSIL and invasive carcinoma. Cut-off of 7.5 for MN counting gave a sensitivity of 89.6% and a specificity of 66.7% (P = 0.024 and AUC = 0.892) for detecting HSIL and invasive carcinoma lesions. Multiple linear regression analysis showed that only HSIL and invasive cancer lesions not age, duration of marital life and number of pregnancy are significantly associated with MN counting. The positive rate of high risk HPV was distinctly higher in LSIL, HSIL and invasive cancer than that in non-neoplstic categories. In conclusions, MN evaluation may be viewed as an effective biomarker for cervical cancer screening. The combination of MN count with HPV DNA detection and TCT may serve as an effective means to screen precancerous cervical lesions in most developing nations.

Immunodeficiency and the risk of cervical intraepithelial neoplasia 2/3 and cervical cancer: A nested case-control study in the Swiss HIV cohort study.

PubMed

Clifford, Gary M; Franceschi, Silvia; Keiser, Olivia; Schöni-Affolter, Franziska; Lise, Mauro; Dehler, Silvia; Levi, Fabio; Mousavi, Mohsen; Bouchardy, Christine; Wolfensberger, Aline; Darling, Katharine E; Staehelin, Cornelia; Bertisch, Barbara; Kuenzli, Esther; Bernasconi, Enos; Pawlita, Michael; Egger, Matthias

2016-04-01

HIV-infected women are at increased risk of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening and immunodeficiency. A case-control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985-2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir [odds ratio (OR) per 100-cell/μL decrease = 1.15, 95% CI: 1.08, 1.22], or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200-349 versus ≥350 cells/μL (OR = 1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2-year cART use was seen against CIN2/3 (OR versus never cART use = 0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 vs. >350 cells/μL= 11.10, 95% CI: 1.24, 100). HPV16-L1 antibodies were significantly associated with CIN2/3, but HPV16-E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts, is a significant risk factor for CIN2/3 and cervical cancer. © 2015 UICC.

Penile carcinogenesis in a low-incidence area: a clinicopathologic and molecular analysis of 115 invasive carcinomas with special emphasis on chronic inflammatory skin diseases.

PubMed

Mannweiler, Sebastian; Sygulla, Stephan; Beham-Schmid, Christine; Razmara, Yas; Pummer, Karl; Regauer, Sigrid

2011-07-01

Human papillomavirus (HPV) infections account worldwide for 50% of penile cancers. The role of lichen sclerosus and lichen planus in penile carcinogenesis needs further investigation. Archival formalin-fixed high-grade penile intraepithelial neoplasias, differentiated penile intraepithelial neoplasias, and invasive carcinomas from a single pathology institution in a low-incidence area for penile cancer were analyzed for 28 HPV low-risk and HPV high-risk genotypes, p16 overexpression, presence of peritumoral lichen sclerosus, lichen planus, precursor lesions, and monoclonal rearrangement of the T-cell receptor γ locus. A total of 29 penile intraepithelial neoplasias (100%) and 69 of 115 (60%) invasive cancers contained HPV high-risk genotypes with a single HPV high-risk genotype (80% HPV16, 6% HPV33, 2% HPV45 and HPV18, 1% HPV73). Multiple HPV high-risk genotypes were identified in 4% with and in 5% without HPV16/18. p16 overexpression correlated in all but 1 case of HPV high-risk 45 cancer. No p16 overexpression and HPV genotype was found in 6 differentiated penile intraepithelial neoplasias and 46 of 115 (40%) invasive cancers, 30% of which were pT2/pT3 cancers. For 35 cancers, peritumoral tissue was available for analysis. Advanced lichen sclerosus was identified in 26, lichen planus in 9, and differentiated penile intraepithelial neoplasia in 18 carcinomas. Dense T-cell-dominant lymphocytic infiltrates were identified in 22 of 46 carcinomas and in 3 of 6 differentiated penile intraepithelial neoplasias, with 6 of 13 analyzed carcinomas/penile intraepithelial neoplasias showing a monoclonal rearrangement of the T-cell receptor γ locus. The prevalence of HPV high-risk in penile cancers from a low-incidence area was slightly higher than the global distribution. HPV-negative carcinomas were associated with advanced lichen sclerosus and lichen planus, differentiated penile intraepithelial neoplasia, and accumulation of T lymphocytes with monoclonal rearrangement of

Risk of head-and-neck cancer following a diagnosis of severe cervical intraepithelial neoplasia: a nationwide population-based cohort study in Denmark.

PubMed

Svahn, M F; Munk, C; Jensen, S M; von Buchwald, C; Frederiksen, K; Kjaer, S K

2016-07-01

Women with a history of cervical intraepithelial neoplasia grade 3 including adenocarcinoma in situ (CIN3/AIS) may be more prone to develop cancers of the ano-genital region and head-and-neck cancers. The current literature is, however, limited. We established a nationwide cohort of approximately 2,500,000 Danish women born in 1918-1990. By linking the cohort to population-based health registries, we obtained information on CIN3/AIS, cancer, migration, death, education, and smoking. Cox proportional hazards models were used to estimate hazard ratios (HRs) and confidence intervals (CIs) for the association between CIN3/AIS and risk of head-and-neck squamous cell carcinoma (HNSCC). HRs were presented for any HNSCC and for four subgroups categorized by their anticipated degree of association with human papillomavirus (HPV). A history of CIN3/AIS was significantly associated with an increased overall relative risk of HNSCC after adjustment for year of birth, attained age, and length of education. The risk was especially high for sites anticipated to be strongly associated with HPV (e.g. base of tongue, tonsils) (HR, 2.49; 95% CI, 1.84-3.36). Lower risks were found for sites anticipated to be not or weakly associated with HPV (e.g. nasal cavity, middle ear, sinuses) (HR, 1.29; 95% CI, 0.61-2.76). Women with a history of CIN3/AIS have a significantly higher risk of HNSCC than women without such a history. The increased relative risk persisted for at least 20years after the CIN3/AIS diagnosis. Women with CIN3/AIS may be more susceptible to the consequences of HPV and/or may have higher risk behavior, such as smoking. Copyright © 2016 Elsevier Inc. All rights reserved.

Recurrence of vulval intraepithelial neoplasia following treatment with cidofovir or imiquimod: results from a multicentre, randomised, phase II trial (RT3VIN).

PubMed

Hurt, C N; Jones, Sef; Madden, T-A; Fiander, A; Nordin, A J; Naik, R; Powell, N; Carucci, M; Tristram, A

2018-01-16

To compare the recurrence rates after complete response to topical treatment with either cidofovir or imiquimod for vulval intraepithelial neoplasia (VIN) 3. A prospective, open, randomised multicentre trial. 32 general hospitals located in Wales and England. 180 patients were randomised consecutively between 21 October 2009 and 11 January 2013, 89 to cidofoovir (of whom 41 completely responded to treatment) and 91 to imiquimod (of whom 42 completely responded to treatment). After 24 weeks of treatment, complete responders were followed up at 6-monthly intervals for 24 months. At each visit, the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was assessed and any new lesions were biopsied for histology. Time to histologically confirmed disease recurrence (any grade of VIN). The median length of follow up was 18.4 months. At 18 months, more participants were VIN-free in the cidofovir arm: 94% (95% CI 78.2-98.5) versus 71.6% (95% CI 52.0-84.3) [univariable hazard ratio (HR) 3.46, 95% CI 0.95-12.60, P = 0.059; multivariable HR 3.53, 95% CI 0.96-12.98, P = 0.057). The number of grade 2+ events was similar between treatment arms (imiquimod: 24/42 (57%) versus cidofovir: 27/41 (66%), χ2 = 0.665, P = 0.415), with no grade 4+. Long-term data indicates a trend towards response being maintained for longer following treatment with cidofovir than with imiquimod, with similar low rates of adverse events for each drug. Adverse event rates indicated acceptable safety of both drugs TWEETABLE ABSTRACT: Long-term follow up in the RT3VIN trial suggests cidofovir may maintain response for longer than imiquimod. © 2018 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.

Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance

PubMed Central

Shi, Yong-Hua; Wang, Bo-Wei; Tuokan, Talaf; Li, Qiao-Zhi; Zhang, Ya-Jing

2015-01-01

A micronucleus is an additional small nucleus formed due to chromosomes or chromosomal fragments fail to be incorporated into the nucleus during cell division. In this study, we assessed the utility of micronucleus counting as a screening tool in cervical precancerous lesions in Thinprep cytological test smears under oil immersion. High risk HPV was also detected by hybrid capture-2 in Thinprep cytological test smears. Our results showed that micronucleus counting was significantly higher in high-grade squamous intraepithelial lesion (HSIL) and invasive carcinoma cases compared to low-grade squamous intraepithelial lesion (LSIL) and non-neoplastic cases. Receiver operating characteristic (ROC) curve analysis revealed that micronucleus counting possessed a high degree of sensitivity and specificity for identifying HSIL and invasive carcinoma. Cut-off of 7.5 for MN counting gave a sensitivity of 89.6% and a specificity of 66.7% (P = 0.024 and AUC = 0.892) for detecting HSIL and invasive carcinoma lesions. Multiple linear regression analysis showed that only HSIL and invasive cancer lesions not age, duration of marital life and number of pregnancy are significantly associated with MN counting. The positive rate of high risk HPV was distinctly higher in LSIL, HSIL and invasive cancer than that in non-neoplstic categories. In conclusions, MN evaluation may be viewed as an effective biomarker for cervical cancer screening. The combination of MN count with HPV DNA detection and TCT may serve as an effective means to screen precancerous cervical lesions in most developing nations. PMID:26339413

Inflammation and Atrophy Precede Prostate Neoplasia in PhIP Induced Rat Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borowsky, A D; Dingley, K; Ubick, E

2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) has been implicated as a major mutagenic heterocyclic amine in the human diet and is carcinogenic in the rat prostate. In order to validate PhIP induced rat prostate neoplasia as a model of human prostate cancer progression, we sought to study the earliest histologic and morphologic changes in the prostate and to follow the progressive changes over time. We fed 67 male Fischer F344 5 week old rats with PhIP (400 PPM) or control diets for 20 weeks, and then sacrificed animals for histomorphologic examination at age 25 weeks, 45 weeks, and 65 weeks. Animals treated with PhIPmore » showed significantly more inflammation (P=.002 (25wk), >.001(45wk), .016(65wk)) and atrophy (P=.003(25wk), >.001(45wk), .006 (65wk)) in their prostate glands relative to controls. Prostatic intraepithelial neoplasia (PIN) occurred only in PhIP treated rats. PIN lesions arose in areas of glandular atrophy, most often in the ventral prostate. Atypical cells in areas of atrophy show loss of glutathione S-transferase pi immunostaining preceding development of PIN. None of the animals in this study developed invasive carcinomas differing from previous reports. Overall, these findings suggest that the pathogenesis of prostatic neoplasia in the PhIP treated rat prostate proceeds from inflammation to post-inflammatory proliferative atrophy to PIN.« less

Co-expression of HSV2 and Chlamydia trachomatis in HPV-positive cervical cancer and cervical intraepithelial neoplasia lesions is associated with aberrations in key intracellular pathways.

PubMed

Paba, Pierpaolo; Bonifacio, Daniela; Di Bonito, Luigi; Ombres, Domenico; Favalli, Cartesio; Syrjänen, Kari; Ciotti, Marco

2008-01-01

Oncogenic human papillomaviruses (HPVs) are the etiological agents of cervical cancer. Different cofactors might be needed for malignant transformation, but they still remain elusive. To delineate the role of Chlamydia trachomatis (CT) and herpes simplex virus type 2 (HSV2) in HPV-positive cervical intraepithelial neoplasia (CIN) lesions and cervical carcinoma a series of 149 cervical cancer and CIN biopsies were analyzed for CT and HSV2 DNA by PCR, and HPV genotyped by InnoLipa. Monitoring of aberrations in key intracellular pathways due to CT/HSV2 and HPV co-expression were analyzed with 13 biomarkers. Of the 149 samples tested, 136 were HPV DNA positive; 32/136 contained also CT DNA and 29 HSV2 DNA. Detection of CT was significantly (p = 0.0001) related to multiple-type HPV infections, while HSV2 was of borderline significance (p = 0.053). Of the 13 biomarkers tested, cytoplasmic and nuclear NF-kappaB and VEGF-C were significantly increased in CT+/HPV+ lesions; p = 0.023, p = 0.045, and p = 0.020 as well as survivin, p = 0.026. Survivin was the only marker that was overexpressed also in HSV2+/HPV+ lesions, p = 0.027. CT infection favors the entry and persistence of multiple HR-HPV types, which leads to viral integration, inhibition of apoptosis, overexpression of E6/E7 oncogenes and cell transformation. Copyright 2008 S. Karger AG, Basel.

Risk factors for under-diagnosis of gastric intraepithelial neoplasia and early gastric carcinoma in endoscopic forceps biopsy in comparison with endoscopic submucosal dissection in Chinese patients.

PubMed

Xu, Guifang; Zhang, Weijie; Lv, Ying; Zhang, Bin; Sun, Qi; Ling, Tingsheng; Zhang, Xiaoqi; Zhou, Zhihua; Wang, Lei; Huang, Qin; Zou, Xiaoping

2016-07-01

Differences in pathologic diagnosis between endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) for gastric intraepithelial neoplasia (GIN) and early gastric carcinoma (EGC) in Chinese patients remain unknown. The aim of the study was to investigate risk factors for under-diagnosed pathology in initial EFB, compared to final ESD. We reviewed endoscopic and histopathologic findings for tumor location, size, macroscopic pattern, nodularity, erythema, erosion, GIN (low and high grade), and EGC diagnosed with the WHO criteria. Differences in those features between EFB and ESD were compared and risk factors for under-diagnosis by EFB were analyzed. Although concordant in most (74.9 %) cases between EFBs and ESDs, pathological diagnoses in 57 (25.1 %) cases were upgraded in ESDs. Compared to the concordant group, the lesion size ≥2 cm, and depressed and excavated patterns were significantly more frequent in the upgraded group. Further multivariate regression analysis demonstrated the depressed pattern and lesion size ≥2 cm as independent risk factors for upgraded pathology with the odds ratio of 5.778 (95 % confidence interval 2.893-11.542) and 2.535 (95 % confidence interval 1.257-5.111), respectively. Lesion size ≥2.0 cm and the depressed pattern at initial EFB were independent risk factors for pathologic upgrade to advanced diseases in ESD. Therefore, these endoscopic characteristics should be considered together with the initial EFB diagnosis to guide the optimal clinical management of patients with GIN and EGC.

Factors influencing histologic confirmation of high-grade squamous intraepithelial lesion cytology.

PubMed

Castle, Philip E; Cox, J Thomas; Schiffman, Mark; Wheeler, Cosette M; Solomon, Diane

2008-09-01

To examine the predictors of histologic confirmation of high-grade squamous intraepithelial lesion (HSIL) cytology occurring in follow-up of young women originally referred into a trial because of less severe cytology. We used enrollment HSIL cytology (N=411) as read by clinical center pathologists for women participating in the ASCUS-LSIL Triage Study (ALTS). The primary outcome was histologic cervical intraepithelial neoplasia (CIN) grade 3 and early cancer (n=195; 191 CIN 3 and four cancers) as diagnosed by the Pathology Quality Control Group during the 2-year duration of ALTS. The 2-year absolute risk of CIN 3 or worse after an HSIL cytology was 47.4% (95% confidence interval 42.5-52.4%). The 2-year absolute risk of CIN 3 or worse was lowest (14.3%) for women who were human papillomavirus (HPV)-16-negative, had colposcopic impression of less than low-grade, and whose HSIL cytology as called by the clinical center was not also called HSIL or equivocal HSIL cytology by the Pathology Quality Control Group. The 2-year absolute risk of CIN 3 or worse was highest (82.4%) for women who were HPV16-positive, had colposcopic impression of low-grade or worse, and whose HSIL cytology also was called HSIL or equivocal HSIL cytology by the Pathology Quality Control Group. Histologic confirmation of precancer among young women with HSIL cytology was more likely when other risk factors (eg, HPV16) for cervical precancer were present.

In the absence of (early) invasive carcinoma, vulvar intraepithelial neoplasia associated with lichen sclerosus is mainly of undifferentiated type: new insights in histology and aetiology.

PubMed

van Seters, M; ten Kate, F J W; van Beurden, M; Verheijen, R H M; Meijer, C J L M; Burger, M P M; Helmerhorst, T J M

2007-05-01

Differentiated vulvar intraepithelial neoplasia (VIN) is presumed to be the precursor of invasive squamous cell carcinoma (SCC) of the vulva. It is commonly assumed that differentiated VIN is related to lichen sclerosus (LS). However, evidence for this is limited to a small number of studies describing epithelial alterations adjacent to vulvar SCC. To study the histology and human papillomavirus (HPV) status in patients with a history of both LS and VIN without coexistent SCC. Original biopsy specimens and surgical specimens of patients retrieved from the pathology files were revised for the presence of LS, VIN and (early) invasive SCC, specifically focused on the two different types of VIN: differentiated and undifferentiated. Thereafter, VIN lesions were tested for the presence of HPV DNA. Twenty-seven patients fulfilled the criteria for LS and VIN without SCC. In all 27 patients, LS was found to be related to undifferentiated VIN. Grading yielded the following results: VIN 1 (n=10), VIN 2 (n=11) and VIN 3 (n=6). Additionally, VIN lesions from 26 patients could be tested for the presence of HPV DNA. HPV DNA, predominantly type 16, was present in 8 (31%) of them. Seven of these eight patients had VIN 2 or 3. During follow-up, three patients progressed to (early) invasive carcinoma. In two of these patients, differentiated VIN was observed overlying early invasive SCC. VIN related to LS without coexisting SCC is likely to be undifferentiated, in contrast to what was previously thought. HPV DNA was demonstrated in 31% of the lesions, and was strongly related to high-grade VIN.

Clinical Outcomes after Conservative Management of Cervical Intraepithelial Neoplasia Grade 2 (CIN2) in Women Ages 21-39 Years.

PubMed

Silver, Michelle I; Gage, Julia C; Schiffman, Mark; Fetterman, Barbara; Poitras, Nancy E; Lorey, Thomas; Cheung, Li C; Katki, Hormuzd A; Locke, Alexander; Kinney, Walter K; Castle, Philip E

2018-03-01

Cervical intraepithelial neoplasia grade 2 (CIN2) frequently regresses, is typically slow-growing, and rarely progresses to cancer. Some women forgo immediate treatment, opting for conservative management (heightened surveillance with cytology and colposcopy), to minimize overtreatment and increased risk of obstetric complications; however, there are limited data examining clinical outcomes in these women. We performed a retrospective cohort analysis of younger women diagnosed with initially untreated CIN1/2, CIN2 and CIN2/3 lesions at Kaiser Permanente Northern California between 2003 and 2015. Clinical outcomes were categorized into five mutually exclusive hierarchical groups: cancer, treated, returned to routine screening, persistent high-grade lesion, or persistent low-grade lesion. Median follow-up for the 2,417 women was 48 months. Six women were diagnosed with cancer (0.2%), all with history of high-grade cytology, and none after a negative cotest. Thirty percent of women were treated, and only 20% returned to routine screening; 50% remained in continued intensive follow-up, of which 86% had either low-grade cytology/histology or high-risk human papillomavirus (HPV) positivity, but not necessarily persistence of a single HPV type. No cancers were detected after a single negative cotest in follow-up. Almost half of initially untreated women did not undergo treatment, but remained by protocol in colposcopy clinic for 2 or more years in the absence of persisting CIN2 + Their incomplete return to total negativity was possibly due to sequential new and unrelated low-grade abnormalities. The prolonged colposcopic surveillance currently required to return to routine screening in the absence of persisting CIN2 + might not be necessary after a negative cotest. Significance: Many younger women under conservative management following an initial CIN2 result remain in a clinical protocol of prolonged intensified surveillance without a subsequent diagnosis of CIN2 or more

Human Papillomavirus (HPV) Genotypes in Condylomas, Intraepithelial Neoplasia, and Invasive Carcinoma of the Penis Using Laser Capture Microdissection (LCM)-PCR: A Study of 191 Lesions in 43 Patients.

PubMed

Fernández-Nestosa, María J; Guimerà, Nuria; Sanchez, Diego F; Cañete-Portillo, Sofía; Velazquez, Elsa F; Jenkins, David; Quint, Wim; Cubilla, Antonio L

2017-06-01

Laser capture microdissection-polymerase chain reaction (LCM-PCR) supported by p16 was used for the first time to demonstrate human papillomavirus (HPV) DNA in histologically specific penile lesions, which were as follows: squamous hyperplasia (12 lesions, 10 patients), flat lesions (12 lesions, 5 patients), condylomas (26 lesions, 7 patients), penile intraepithelial neoplasia (PeIN) (115 lesions, 43 patients), and invasive squamous cell carcinomas (26 lesions, 26 patients). HPV was detected by whole-tissue section and LCM-PCR. LCM proved to be more precise than whole-tissue section in assigning individual genotypes to specific lesions. HPV was negative or very infrequent in squamous hyperplasia, differentiated PeIN, and low-grade keratinizing variants of carcinomas. HPV was strongly associated with condylomas, warty/basaloid PeIN, adjacent flat lesions, and warty/basaloid carcinomas. A single HPV genotype was found in each lesion. Some condylomas and flat lesions, especially those with atypia, were preferentially associated with high-risk HPV. Unlike invasive carcinoma, in which few genotypes of HPV were involved, there were 18 HPV genotypes in PeIN, usually HPV 16 in basaloid PeIN but marked HPV heterogeneity in warty PeIN (11 different genotypes). Variable and multiple HPV genotypes were found in multicentric PeIN, whereas unicentric PeIN was usually related to a single genotype. There was a correspondence among HPV genotypes in invasive and associated PeIN. p16 was positive in the majority of HPV-positive lesions except condylomas containing LR-HPV. p16 was usually negative in squamous hyperplasia, differentiated PeIN, and low-grade keratinizing variants of squamous cell carcinomas. In summary, we demonstrated that LCM-PCR was a superior research technique for investigating HPV genotypes in intraepithelial lesions. A significant finding was the heterogeneity of HPV genotypes in PeIN and the differential association of HPV genotypes with subtypes of PeIN. The

Eukaryotic initiation factor 5A-1 (eIF5A-1) as a diagnostic marker for aberrant proliferation in intraepithelial neoplasia of the vulva.

PubMed

Cracchiolo, Bernadette M; Heller, Debra S; Clement, Paul M J; Wolff, Edith C; Park, Myung-Hee; Hanauske-Abel, Hartmut M

2004-07-01

The mature eukaryotic translation initiation factor 5A contains the unusual amino acid hypusine, formed post-translationally from a specific lysine residue and essential for proliferation of eukaryotic cells. We hypothesized that the major eIF5A isoform, eIF5A-1, is an in situ biomarker for proliferation. NIH-353, a polyclonal immunoreagent specific for hypusine-containing eIF5A-1, was used to test this proposal in biopsies of vulvar high-grade intraepithelial neoplasia (VIN), characterized by the presence of proliferating cells throughout the thickness of the epithelium. Methods. Formalin-fixed and paraffin-embedded archival samples with an independently established diagnosis of VIN 3 were stained immunohistochemically after antigen retrieval, employing NIH-353 and, for comparison, the standard Ki-67 antibody. NIH-353 labeled neoplastic keratinocytes throughout the thickness of the epithelium in all VIN 3 samples. Malignant cells in a case of focally invasive squamous cell carcinoma also stained strongly for mature, hypusine-containing eIF5A-1. Epithelium adjacent to these lesions, though still of apparently normal morphology, was immunoreactive throughout its full thickness. At inflammatory foci of lesional sites, solitary reactive lymphocytes were positive, as were individual proliferating cells within dermal appendages. The submucosal stroma lacked reactive cells. NIH-353 identifies mature eIF5A-1 as an in situ biomarker for proliferation. Like Ki-67, this immunoreagent promises broad applicability in histopathological diagnosis and may be helpful in outcome prediction. In contrast to Ki-67, NIH-353 visualizes a molecular target for antineoplastic therapy, and thus may guide the development and clinical testing of drugs that, like the fungicide ciclopirox, inhibit hypusine formation and cell proliferation.

Long-Term Outcomes of Adding HPV Vaccine to the Anal Intraepithelial Neoplasia Treatment Regimen in HIV-Positive Men Who Have Sex With Men

PubMed Central

Deshmukh, Ashish A.; Chhatwal, Jagpreet; Chiao, Elizabeth Y.; Nyitray, Alan G.; Das, Prajnan; Cantor, Scott B.

2015-01-01

Background. Recent evidence shows that quadrivalent human papillomavirus (qHPV) vaccination in men who have sex with men (MSM) who have a history of high-grade anal intraepithelial neoplasia (HGAIN) was associated with a 50% reduction in the risk of recurrent HGAIN. We evaluated the long-term clinical and economic outcomes of adding the qHPV vaccine to the treatment regimen for HGAIN in human immunodeficiency virus (HIV)–positive MSM aged ≥27 years. Methods. We constructed a Markov model based on anal histology in HIV-positive MSM comparing qHPV vaccination with no vaccination after treatment for HGAIN, the current practice. The model parameters, including baseline prevalence, disease transitions, costs, and utilities, were either obtained from the literature or calibrated using a natural history model of anal carcinogenesis. The model outputs included lifetime costs, quality-adjusted life years, and lifetime risk of developing anal cancer. We estimated the incremental cost-effectiveness ratio of qHPV vaccination compared to no qHPV vaccination and decrease in lifetime risk of anal cancer. We also conducted deterministic and probabilistic sensitivity analyses to evaluate the robustness of the results. Results. Use of qHPV vaccination after treatment for HGAIN decreased the lifetime risk of anal cancer by 63% compared with no vaccination. The qHPV vaccination strategy was cost saving; it decreased lifetime costs by $419 and increased quality-adjusted life years by 0.16. Results were robust to the sensitivity analysis. Conclusions. Vaccinating HIV-positive MSM aged ≥27 years with qHPV vaccine after treatment for HGAIN is a cost-saving strategy. Therefore, expansion of current vaccination guidelines to include this population should be a high priority. PMID:26223993

Cytologically diagnosed Gardnerella vaginalis infection and cervical (pre)neoplasia as established in population-based cervical screening.

PubMed

Klomp, Johanna M; Boon, Mathilde E; Van Haaften, Maarten; Heintz, A Peter M

2008-11-01

Cervical inflammation has been proposed as a cofactor in the development of cervical cancer. The purpose of this study was to document the prevalence of cervical (pre)neoplastic changes in asymptomatic women with a cytologically diagnosed Gardnerella vaginalis infection. Data were collected from 800,498 Dutch asymptomatic women, participating in the Dutch national screening program. Prevalences of (pre)neoplasia were calculated for G vaginalis smears using a healthy flora as reference. The prevalence of G vaginalis infection was 0.6 per thousand. The odds ratio for (pre)neoplasia was significantly higher in smears with G vaginalis infection compared with smears of women with a healthy vaginal flora (odds ratio, 10.3; 95% confidence interval, 6.6-16.1). Cytologically diagnosed G vaginalis smears show a strong covariation with the presence of cervical (pre)neoplasia. Future research should therefore focus on the exact causal relation between cytologic G vaginalis infection and the presence of (pre)neoplastic changes of the cervix.

Cervical squamous intraepithelial lesions and associated cervical infections in an HIV-positive population in Rural Mpumalanga, South Africa.

PubMed

Swanepoel, P J; Michelow, P; Du Plessis, R; Proudfoot, I G; Tarr, G A; Bockel, S L; Swanepoel, C J

2013-08-01

The incidences of genital human papillomavirus (HPV) infection, associated squamous intraepithelial lesions and cervical squamous cell carcinoma are significantly increased in HIV-positive women. The role of other cervicovaginal infections in the acquisition of the HPV infection, cervical carcinogenesis and genital HIV infection remains largely speculative. A retrospective study was conducted including 1087 HIV-positive women in rural Mpumalanga province, South Africa, for the period 1 May 2009 to 31 August 2010. For each patient, the age at first presentation, cervical cytological diagnosis, subsequent follow-up cytology and histology, and microscopically visible infections (including endemic Bilharzia) were tabulated and statistically analysed. The prevalence of low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), squamous cell carcinoma, atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells, cannot exclude HSIL (ASC-H) in the study population were 22.1%, 30.9%, 0.6%, 13.5% and 4.0%, respectively. LSIL, HSIL and squamous cell carcinoma were diagnosed, respectively, at the average ages of 35.7, 37.9 and 37.2 years. Four patients with cervical intraepithelial neoplasia grade 1 (CIN1), 32 with CIN2/CIN3 and two with cervical squamous cell carcinoma were also diagnosed with Bilharzia. Of the other infections only bacterial vaginosis had a positive statistical correlation with HPV-induced cervical abnormalities (LSIL, HSIL or squamous cell carcinoma). This study confirms the high prevalence of progressive HPV-associated cervical disease in a rural Southern African HIV-positive population, which is at least equal to or worse than in other African HIV-positive studies. The high incidence of Bilharzia infection in those cases that underwent cervical cone excision suggests a possible relationship with progressive HPV disease and cervical carcinogenesis. Bacterial vaginosis (perhaps in

p16 Expression and Biological Behavior of Flat Vulvar Low-grade Squamous Intraepithelial Lesions (LSIL).

PubMed

Lewis, Natasha; Blanco, Luis Z; Maniar, Kruti P

2017-09-01

Flat low-grade squamous intraepithelial lesion (LSIL) of the vulva [vulvar intraepithelial neoplasia (VIN) 1, flat condyloma] is an uncommon entity with poorly understood biological behavior. We aimed to determine the risk of subsequent vulvar high-grade squamous intraepithelial lesion (HSIL) or carcinoma following a diagnosis of vulvar LSIL/VIN 1, as well as the frequency and predictive value of p16 immunohistochemical expression in this setting. Of the 51 included cases, p16 positivity (diffuse block staining) was identified in 2 (4%). Follow-up data were available in 34 cases, of which 2 (5.9%) developed subsequent vulvar HSIL, including 1/2 p16-positive cases and 1/32 p16-negative cases. The difference in HSIL frequency between p16-positive and p16-negative cases was not statistically significant (P=0.116 for VIN 2+, P=0.061 for VIN 3). For the 18 patients with treatment information available, 10 (56%) received medical or surgical treatment after biopsy. Our results indicate that flat vulvar LSIL is infrequently p16 positive, and that few patients with vulvar LSIL develop subsequent vulvar HSIL. Despite the use of destructive treatment in some cases, the data provide support for the nonpreneoplastic nature of the entity. Immunohistochemical expression of p16 may not be a predictor of HSIL risk in vulvar LSIL, although this result may also be related to the very low rates of both p16 positivity and subsequent vulvar HSIL in our sample. It is clear that vulvar LSIL is distinct from LSIL in other lower anogenital sites in terms of its behavior and p16 expression frequency.

A survey on the prevalence of high-risk subtypes of human papilloma virus among women with cervical neoplasia in Isfahan University of Medical Science.

PubMed

Allameh, Tajossadat; Moghim, Sharareh; Asadi-Zeidabadi, Maryam

2011-12-01

Given the importance of epidemiological studies on the prevalence of human papilloma virus (HPV) and its subtypes to plan more effective strategies for cervical cancer prevention, the aim of this study was to determine the prevalence of HPV in women with cervical intraepithelial neoplasia and cancer in Isfahan. In this descriptive cross-sectional study, women referred to oncology clinic of Shahid Beheshti Hospital because of abnormal cytology of their cervices within the last year were studied. The 2001 Bethesda system was used for histologic classification. The distribution of different pathologies was as follows: squamous cell carcinoma (SCC) 34.7%, low-grade squamous intraepithelial lesions (LSIL) 30.5%, high-grade squamous intraepithelial lesions (HSIL) 22.8%, atypical squamous cell of undetermined significance (ASCUS) 8.4%, and adenocarcinoma (AC) 3.3%. There was no case of atypical glandular of undetermined significance or cases of adenocarcinoma associated with an early lesion. The presence of HPV infection and its subtypes including HPV 16, 18, 6 and 11 was assessed in different cytological categories of cervical neoplasia, by using polymerase chain reaction method. During this study, 130 patients were studied. Their median age was 52 years (range 29-73 years). HPV was detected in 118/130 patients (90.8%) with abnormal cervical cytology. The prevalence of positive HPV samples was 97.6, 80, 93.1, 92.3, and 66.6% in cases with SCC, AC, HSIL, LSIL, and ASCUS, respectively (P < 0.05 between SCC and ASCUS, HSIL and ASCUS, and LSIL and ASCUS). Out of 118 cases with positive HPV, 98 (83.1%) were positive for multiple HPV types 16, 18, and 11 or 6. The distribution of studied HPV subtypes among women with positive HPV was as follows: 49.1% for both types 16 and 18, 10.1% for type 16, 1.69% for type 18 and 22% for type 11 or 6. The prevalence of HPV type 16 was not significantly different in various cytological categories of cervical neoplasia (P > 0.05). The

In the absence of (early) invasive carcinoma, vulvar intraepithelial neoplasia associated with lichen sclerosus is mainly of undifferentiated type: new insights in histology and aetiology

PubMed Central

van Seters, M; Kate, F J W ten; van Beurden, M; Verheijen, R H M; Meijer, C J L M; Burger, M P M; Helmerhorst, T J M

2007-01-01

Background Differentiated vulvar intraepithelial neoplasia (VIN) is presumed to be the precursor of invasive squamous cell carcinoma (SCC) of the vulva. It is commonly assumed that differentiated VIN is related to lichen sclerosus (LS). However, evidence for this is limited to a small number of studies describing epithelial alterations adjacent to vulvar SCC. Aim To study the histology and human papillomavirus (HPV) status in patients with a history of both LS and VIN without coexistent SCC. Methods Original biopsy specimens and surgical specimens of patients retrieved from the pathology files were revised for the presence of LS, VIN and (early) invasive SCC, specifically focused on the two different types of VIN: differentiated and undifferentiated. Thereafter, VIN lesions were tested for the presence of HPV DNA. Results Twenty‐seven patients fulfilled the criteria for LS and VIN without SCC. In all 27 patients, LS was found to be related to undifferentiated VIN. Grading yielded the following results: VIN 1 (n = 10), VIN 2 (n = 11) and VIN 3 (n = 6). Additionally, VIN lesions from 26 patients could be tested for the presence of HPV DNA. HPV DNA, predominantly type 16, was present in 8 (31%) of them. Seven of these eight patients had VIN 2 or 3. During follow‐up, three patients progressed to (early) invasive carcinoma. In two of these patients, differentiated VIN was observed overlying early invasive SCC. Conclusions VIN related to LS without coexisting SCC is likely to be undifferentiated, in contrast to what was previously thought. HPV DNA was demonstrated in 31% of the lesions, and was strongly related to high‐grade VIN. PMID:16714399

Methodological study to evaluate the psychometric properties of FACIT-CD in a sample of Brazilian women with cervical intraepithelial neoplasia.

PubMed

Fregnani, Cristiane Menezes Sirna; Fregnani, José Humberto Tavares Guerreiro; Longatto-Filho, Adhemar

2017-10-16

The occurrence of cervical intraepithelial neoplasia (CIN) is associated with changes in health-related quality of life, including psychological factors, such as fear and shame, and changes in sexuality and sexual satisfaction, such as decreased sexual desire and frequency of sexual intercourse. Personal relationships are the most affected because CIN is sexually transmitted and many women tend to blame their partner for disease transmission. The aim of this study was to evaluate the psychometric properties of the FACIT-CD questionnaire in Brazilian women diagnosed with CIN. The properties of the FACIT-CD questionnaire were tested on a sample of 439 women seen at the Department of Prevention of Barretos Cancer Hospital, including 329 patients who were diagnosed with CIN and 110 women who were not diagnosed with the disease. The analysed parameters included internal consistency (Cronbach's alpha), reproducibility (intraclass correlation coefficient), structural validity, convergent validity (correlation with the SF-12 and EORTC QLQ-CX24 questionnaires), discriminant validity (according to disease status, and self-rating of health), sensitivity, and responsiveness. The Cronbach alpha values ​​of the FACIT-CD scales were higher than 0.70 with the exception of the relationship scale (0.66). The FACIT-CD reproducibility was satisfactory, with variation in the intraclass correlation coefficients ranging between 0.50 and 0.83, although the 95% confidence interval (CI) was lower than 0.40 (0.33-0.64) on the treatment satisfaction scale. Regarding structural validity, only one item on the physical well-being scale was not kept in the original domain. The expected correlations between the FACIT-CD and SF-12 were not confirmed, whereas the correlations between the FACIT-CD and EORTC QLQ-CX24 were confirmed. The questionnaire was able to discriminate the groups according to disease status and self-rating of health. The sensitivity was low for the relationship scale and

Human papillomavirus infection and p16(INK4a) protein expression in vulvar intraepithelial neoplasia and invasive squamous cell carcinoma.

PubMed

Rufforny, Irina; Wilkinson, Edward J; Liu, Chen; Zhu, Haizhen; Buteral, Michael; Massoll, Nicole A

2005-04-01

Vulvar intraepithelial neoplasia (VIN) is defined histopathologically by distinctive abnormalities of cellular maturation and differentiation. The purpose of this study was to investigate the functional properties of VIN related to expression of p16(INK4a) protein as well as to detection of human papillomavirus (HPV) type 16 by real-time polymerase chain reaction (RT-PCR) analysis. A total of 49 vulvar biopsy samples were examined by hematoxylin-eosin staining from benign/reactive lesions, condyloma acuminatum, VIN, and invasive squamous cell carcinoma (SCC). JC8 mouse monoclonal antibodies were used that recognize p16(INK4a) epitope at a dilution of 1:25. The reaction pattern for p16(INK4a) was graded in each sample between 0 and 3+. RT-PCR analysis of formalin-fixed paraffin-embedded sections determined positivity for HPV type 16. p16(INK4a) immunoreactivity was different in VIN 1, VIN 2, VIN 3, and squamous cell carcinoma. Strong expression of p16(INK4a) protein was observed in 92% (22 of 24) of VIN 2 and VIN 3 lesions and 100% (4 of 4) of invasive SCCs. Two (67%) of 3 VIN 2 lesions, 17 (81%) of 21 VIN 3 lesions, and 4 (100%) of 4 SCCs were positive for HPV type 16 by PCR analysis. Two (20%) of 10 VIN 1 lesions were immunoreactive for p16(INK4a), with only 1 lesion positive for HPV type 16. No p16(INK4a) immunoreactivity was observed in any of the benign/reactive and condyloma acuminatum lesions. In addition, none of the benign/reactive or condyloma lesions were positive for HPV type 16 by RT-PCR analysis. Upregulation of INK4a gene occurs in vulvar carcinogenesis. p16(INK4a) is not a sensitive marker for differentiation of benign vulvar squamous epithelium from condyloma acuminatum or VIN 1 lesions because most VIN 1 lesions are p16(INK4a) negative. Expression of p16(INK4a) may aid in the diagnosis of HPV-related lesions and as such may be of value as a surrogate marker in the diagnosis of vulvar premalignant and malignant lesions.

Is self-sampling to test for high-risk papillomavirus an acceptable option among women who have been treated for high-grade cervical intraepithelial neoplasia?

PubMed

Andersson, Sonia; Belkić, Karen; Mints, Miriam; Östensson, Ellinor

2018-01-01

Self-sampling to test for high risk human papilloma virus (HPV) is becoming an increasingly important component of cervical cancer screening. The aim of this observational study is to examine how women treated for high-grade cervical intraepithelial neoplasia (CIN) view HPV self-sampling. Invited to participate in the present study were patients who had undergone treatment of high-grade CIN (grade 2 or higher) and were followed-up at 6-months at the Karolinska University Hospital, Stockholm. The participants were instructed as to how to perform HPV self-sampling. Thereafter, the participants completed a questionnaire about HPV self-sampling and other cervical cancer screening methods, as well as about self-perceived risk of cervical cancer without regular gynecologic follow-up and about specific knowledge regarding HPV, CIN and cervical cancer. Altogether 479 women enrolled in this study. The participation rate was 96.6%. Nearly 75% of the participants stated they would consider performing the HPV self-sampling prior to their next gynecologic follow-up. Confidence in HPV self-sampling was a significant independent predictor of willingness to perform HPV self-sampling. However, confidence in HPV self-sampling was significantly lower than confidence in Papanicolaou smears and in HPV testing with samples collected by health professionals. Higher specific knowledge about HPV, CIN and cervical cancer was also a significant independent predictor of willingness to perform HPV self-sampling, as was having travelled longer distance to attend gynecologic follow-up. Participants with lower income and without completed university education expressed significantly higher confidence in HPV self-sampling and lower confidence in Papanicolaou smears than the other women. To the best of our knowledge, this is the first study to examine the views of women treated for high-grade CIN vis-à-vis HPV self-sampling. The latter is an acceptable option for the vast majority of this cohort

[Preinvasive lesions in gynecology -  vulva].

PubMed

Chovanec, J; Mouková, L; Feranec, R

2013-01-01

For preinvasive lesions of vulva, a common term VIN -  vulval intraepithelial neoplasia is used. VIN is a histological dia-gnosis based on abnormal squamous epithelial proliferation. There are two types of VIN apart from their association with human papillomavirus (HPV). Undifferentiated (usual) vulval intraepithelial neoplasia is commonly associated with carcinogenic genotypes of HVP, whereas differentiated vulval intraepithelial neoplasia is not associated with high-risk genotypes of HPV. The article presents an overview of VIN occurence and epidemiology, its classification system and dia-gnostics. In conclusion, VIN therapeutical possibilities are presented. It can be treated with surgical therapy (local excision, partial vulvectomy, vulvectomy, laser vaporization) or medical therapy (imiquimod).

Neoplasia: The Second Decade

PubMed Central

Rehemtulla, Alnawaz

2008-01-01

This issue marks the end of the 10-year anniversary of Neoplasia where we have seen exciting growth in both number of submitted and published articles in Neoplasia. Neoplasia was first published in 1999. During the past 10 years, Neoplasia has dynamically adapted to the needs of the cancer research community as technologies have advanced. Neoplasia is currently providing access to articles through PubMed Central to continue to facilitate rapid broad-based dissemination of published findings to the scientific community through an Open Access model. This has in part helped Neoplasia to achieve an improved impact factor this past year, demonstrating that the manuscripts published by Neoplasia are of great interest to the overall cancer research community. This past year, Neoplasia received a record number of articles for review and has had a 21% increase in the number of published articles. PMID:19048110

HR-HPV E6/E7 mRNA In Situ Hybridization: Validation Against PCR, DNA In Situ Hybridization, and p16 Immunohistochemistry in 102 Samples of Cervical, Vulvar, Anal, and Head and Neck Neoplasia.

PubMed

Mills, Anne M; Dirks, Dawn C; Poulter, Melinda D; Mills, Stacey E; Stoler, Mark H

2017-05-01

Dysregulated expression of oncogenic types of E6 and E7 is necessary for human papillomavirus (HPV)-driven carcinogenesis. An HPV E6/E7 mRNA in situ hybridization (ISH) assay covering 18 common high-risk types ("HR-RISH," aka HR-HPV RNA18 ISH) has not been extensively studied in the anogenital tract or validated on automated technology. We herein compare HR-RISH to DNA polymerase chain reaction (PCR), p16 immunohistochemistry, and a previously available HPV DNA ISH assay in HPV-related anogenital and head and neck (H&N) neoplasia. A total of 102 squamous intraepithelial lesions (16 CIN1, 25 CIN3, 3 AIN1, 12 AIN3, 9 VIN3)/invasive squamous cell carcinomas (17 cervical, 2 anal, 18 H&N) as well as 10 normal and 15 reactive cervix samples were collected. HR-RISH, DNA ISH, and p16 immunohistochemistry were performed on whole formalin-fixed, paraffin-embedded sections. RNA ISH for 6 low-risk HPV types (LR-RISH) was also performed. RNA and DNA ISH assays used automated systems. HR-HPV PCR was performed on morphology-directed formalin-fixed, paraffin-embedded punches. HR-RISH was ≥97% sensitive for PCR+ and p16+ neoplasia, as well as morphologically defined anogenital high grade squamous intraepithelial lesion/invasive squamous cell carcinoma. HR-RISH was also positive in 78% of anogenital low grade squamous intraepithelial lesion, including 81% of CIN1. Furthermore, a subset of PCR-negative/invalid and p16-negative lesions was positive for HR-RISH. Only 1 problematic reactive cervix sample and no normal cervix samples stained. These results demonstrate that HR-RISH is a robust method for the detection of HR-HPV-related neoplasia and provides insight into HPV pathobiology. Performance meets or exceeds that of existing assays in anogenital and H&N lesions and may play a role in resolving diagnostically challenging CIN1 versus reactive cases.

Reflex Human Papillomavirus Test Results as an Option for the Management of Korean Women With Atypical Squamous Cells Cannot Exclude High-Grade Squamous Intraepithelial Lesion

PubMed Central

Ryu, Ki-Jin; Lee, Sanghoon; Min, Kyung-Jin; Kim, Jae Won; Hong, Jin Hwa; Song, Jae Yun; Lee, Jae Kwan

2015-01-01

Background. Current guidelines recommend initial colposcopy with biopsy regardless of human papillomavirus (HPV) test results in women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H). The purpose of this study was to evaluate the value of HPV testing in women with ASC-H based on colposcopic pathology results. Materials and Methods. A multicenter cross-sectional study was carried out at three academic hospitals and involved 40,847 Korean women who underwent cervical cancer screening with cytology and HPV tests with or without subsequent colposcopic biopsies between January 2007 and December 2013. Results. ASC-H was diagnosed in 276 women (0.7%). Only 6 of 68 (8.8%) women with ASC-H who were HPV negative had cervical intraepithelial neoplasia grade ≥2 (CIN ≥2) lesions, whereas 47.4% of the women with ASC-H who were HPV positive had CIN ≥2 lesions. No cases of invasive cervical cancer were diagnosed among women with ASC-H who were HPV negative. Logistic regression analysis was performed using the group with normal Papanicolaou test results and HPV-negative status as the reference group. Women with ASC-H who were HPV positive had a significantly increased risk of CIN ≥2 lesions, whereas no significant increase was observed in patients with ASC-H and HPV-negative status. Conclusion. If the result of the HPV test was negative, the risk of CIN ≥2 lesions in Korean women with ASC-H cytology was low. Reflex HPV testing should be an option for the management of women with cytology showing ASC-H to decrease unnecessary colposcopic biopsies, which are expensive and invasive. Implications for Practice: Current American Society for Colposcopy and Cervical Pathology guidelines recommend universal colposcopy for the management of women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) on cytology, regardless of human papillomavirus (HPV) test results. The present study suggested

Comparison of Onclarity Human Papillomavirus (HPV) Assay with Hybrid Capture II HPV DNA Assay for Detection of Cervical Intraepithelial Neoplasia Grade 2 and 3 Lesions

PubMed Central

Sideri, M.; Gulmini, C.; Igidbashian, S.; Tricca, A.; Casadio, C.; Carinelli, S.; Boveri, S.; Ejegod, D.; Bonde, J.; Sandri, M. T.

2015-01-01

Analytical and clinical performance validation is essential before introduction of a new human papillomavirus (HPV) assay into clinical practice. This study compares the new BD Onclarity HPV assay, which detects E6/E7 DNA from 14 high-risk HPV types, to the Hybrid Capture II (HC2) HPV DNA test, to concurrent cytology and histology results, in order to evaluate its performance in detecting high-grade cervical lesions. A population of 567 women, including 325 with ≥ASCUS (where ASCUS stands for atypical cells of undetermined significance) and any HC2 result and 242 with both negative cytology and negative HC2 results, were prospectively enrolled for the study. The overall agreement between Onclarity and HC2 was 94.6% (95% confidence intervals [CI], 92.3% to 96.2%). In this population with a high prevalence of disease, the relative sensitivities (versus adjudicated cervical intraepithelial neoplasia grades 2 and 3 [CIN2+] histology endpoints) of the Onclarity and HC2 tests were 95.2% (95% CI, 90.7% to 97.5%) and 96.9% (95% CI, 92.9% to 98.7%), respectively, and the relative specificities were 50.3% (95% CI, 43.2% to 57.4%) for BD and 40.8% (95% CI, 33.9%, 48.1%) for HC2. These results indicate that the BD Onclarity HPV assay has sensitivity comparable to that of the HC2 assay, with a trend to an increased specificity. Moreover, as Onclarity gives the chance to discriminate between the different genotypes, we calculated the genotype prevalence and the absolute risk of CIN2+: HPV 16 was the most prevalent genotype (19.8%) with an absolute risk of CIN2+ of 77.1%. PMID:25903574

FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer

PubMed Central

Andren, Ove; Ohlson, Anna‐Lena; Carlsson, Jessica; Andersson, Swen‐Olof; Giunchi, Francesca; Rider, Jennifer R.; Fiorentino, Michelangelo

2017-01-01

Background The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (Tregs). In the present study we evaluated the prevalence of Treg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer. Methods Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4+ Tregs and CD8+ Tregs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of Tregs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area. Results In men with prostate cancer, similarly high numbers of stromal CD4+ Tregs were identified in PAH and tumor, but CD4+ Tregs were less common in PIN. Greater numbers of epithelial CD4+ Tregs in normal prostatic tissue were positively associated with both Gleason score and pT‐stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4+ Tregs in the normal prostatic tissue counterpart. Conclusions Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4+ Tregs and indicate that transformation of the anti‐tumor immune response may be initiated even before the primary tumor is established. PMID:29105795

Minichromosome maintenance (Mcm) proteins, cyclin B1 and D1, phosphohistone H3 and in situ DNA replication for functional analysis of vulval intraepithelial neoplasia.

PubMed

Davidson, E J; Morris, L S; Scott, I S; Rushbrook, S M; Bird, K; Laskey, R A; Wilson, G E; Kitchener, H C; Coleman, N; Stern, P L

2003-01-27

Vulval intraepithelial neoplasia (VIN) is defined histopathologically by distinctive abnormalities of cellular maturation and differentiation. To investigate the functional properties of VIN, the expression of several proteins involved in the regulation of the cell cycle as well as in situ DNA replication competence was analysed by immunohistochemistry. Snap-frozen vulval biopsies were graded as normal squamous epithelium (n=6), undifferentiated HPV positive VIN 1 (n=3), VIN 2 (n=8) and VIN 3 (n=20). Immunohistochemistry was performed using the following markers: cyclin D1 (expressed in middle/late G1), cyclin B1 (expressed in G2/early M), phosphorylated histone H3 (expressed during mitosis) and minichromosome maintenance (Mcm) proteins 2 and 5 (expressed during the cell cycle, but not in differentiated or quiescent cells). In situ DNA replication competence was used to identify S-phase cells. The percentage of positively stained nuclei in three representative microscopic fields was calculated per biopsy. In normal vulva, the expression of all markers was restricted to the proliferative compartment of the basal layer of the epithelium. In contrast in high-grade VIN, the majority of epithelial cells expressed the Mcm proteins from basal to superficial layer. The detection of cyclins B1 and D1, phospho-histone H3 and in situ DNA replication was also found through the full thickness of these lesions but by a lower proportion of the cells. This is consistent with these markers providing a series of 'snapshots' of the cell cycle status of individual cells. The low-grade VIN showed reduced expression of the cell cycle markers in relation to the level of dysplasia. The combination of these analyses establishes that the majority of VIN cells remain in a functional replicative or prereplicative state of the cell cycle. Clinical application of these analyses may provide a basis for improved diagnosis of VIN.

FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer.

PubMed

Davidsson, Sabina; Andren, Ove; Ohlson, Anna-Lena; Carlsson, Jessica; Andersson, Swen-Olof; Giunchi, Francesca; Rider, Jennifer R; Fiorentino, Michelangelo

2018-01-01

The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (T regs ). In the present study we evaluated the prevalence of T reg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer. Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4 + T regs and CD8 + T regs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of T regs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area. In men with prostate cancer, similarly high numbers of stromal CD4 + T regs were identified in PAH and tumor, but CD4 + T regs were less common in PIN. Greater numbers of epithelial CD4+ T regs in normal prostatic tissue were positively associated with both Gleason score and pT-stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4 + T regs in the normal prostatic tissue counterpart. Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4 + T regs and indicate that transformation of the anti-tumor immune response may be initiated even before the primary tumor is established. © 2017 The Authors. The Prostate Published by Wiley Periodicals Inc.

Computerized image analysis for acetic acid induced intraepithelial lesions

NASA Astrophysics Data System (ADS)

Li, Wenjing; Ferris, Daron G.; Lieberman, Rich W.

2008-03-01

Cervical Intraepithelial Neoplasia (CIN) exhibits certain morphologic features that can be identified during a visual inspection exam. Immature and dysphasic cervical squamous epithelium turns white after application of acetic acid during the exam. The whitening process occurs visually over several minutes and subjectively discriminates between dysphasic and normal tissue. Digital imaging technologies allow us to assist the physician analyzing the acetic acid induced lesions (acetowhite region) in a fully automatic way. This paper reports a study designed to measure multiple parameters of the acetowhitening process from two images captured with a digital colposcope. One image is captured before the acetic acid application, and the other is captured after the acetic acid application. The spatial change of the acetowhitening is extracted using color and texture information in the post acetic acid image; the temporal change is extracted from the intensity and color changes between the post acetic acid and pre acetic acid images with an automatic alignment. The imaging and data analysis system has been evaluated with a total of 99 human subjects and demonstrate its potential to screening underserved women where access to skilled colposcopists is limited.

Chlamydia trachomatis infection and human papillomavirus in women with cervical neoplasia in Pernambuco-Brazil.

PubMed

Tavares, Mayara Costa Mansur; de Macêdo, Jamilly Lopes; de Lima Júnior, Sérgio Ferreira; de Andrade Heráclio, Sandra; Amorim, Melânia Maria Ramos; de Mascena Diniz Maia, Maria; de Souza, Paulo Roberto Eleutério

2014-02-01

Chlamydia trachomatis (CT) is the most common bacterial cause of sexually transmitted disease. High-risk human papillomavirus (HR-HPV) is considered the main etiological agent for cervical neoplasia. Evidences showed that the presence of co-infection of CT and HR-HPV plays a central role in the etiology of cervical intraepithelial neoplasia (CIN) and cervical cancer. The goals of this study were: evaluate the human papillomavirus (HPV) and CT prevalence among Brazilian women with abnormal cytology and provide the effect of this association on the severity of cervical neoplasia. The population of this study was composed by 142 women with incident histological incidence of CIN grades I, II, III or cervical cancer from Recife, Northeast of Brazil. The polymerase chain reaction method on a cervical brush specimen was used to detect both agents and the automatic sequencing method was used for HPV genotyping assay. The prevalence of HPV and CT was 100 and 24.65 %, respectively. Thirteen types of HPV were detected; HPV 16, 18, 31 and 33 were the most common. The most prevalent HPV types were HPV 16 and 18. A significant association between CT positive and HPV 16 infection was found (p < 0.0106; OR = 5.31; 95 % IC 1.59-17.67). In the study population, there was diversity of HPV infections, with high-risk types being the most common. Also, the data collected suggest that CT infection may play an important role in the natural history of HPV infection.

Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical intraepithelial neoplasia and cervical infection in young Japanese women

PubMed Central

Konno, Ryo; Yoshikawa, Hiroyuki; Okutani, Marie; Quint, Wim; V Suryakiran, Pemmaraju; Lin, Lan; Struyf, Frank

2014-01-01

In this open, extended follow-up study (NCT00929526, Clinicaltrials.gov), we evaluated the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine efficacy, immunogenicity and safety up to 4 years after first vaccination in Japanese women aged 20–25 years. In the initial randomized, double-blind study (NCT00316693), 1040 women received the study vaccine or hepatitis A control vaccine; 752 women were included in the follow-up study. In women from the according-to-protocol efficacy cohort (ATP-E), who were initially seronegative for the HPV type analyzed, no cervical intraepithelial neoplasia (CIN) grade 1 or greater (CIN1+) cases associated with HPV-16/18 were reported in the HPV group, while in the control group, 5 cases were identified in extended follow-up analyses (vaccine efficacy [VE] 100% [95% CI: −3.7–100]) and 8 cases in combined initial and follow-up studies analyses (VE 100% [42.2–100]). In the ATP-E, VE against CIN1+ and CIN2+ associated with high-risk HPV types reached 66.4% (21.6–87.1) and 83.0% (22.1–98.2) in extended follow-up analyses, and 63.4% (28.8–82.3) and 77.3% (30.4–94.4) in analyses of combined studies, respectively. During the 4-year period, protection against CIN1+ and CIN2+, irrespective of the HPV type, was 56.7% (32.8–72.6) and 54.9% (20.5–75.3) in women receiving ≥1 vaccine dose, regardless of baseline serostatus (total vaccinated cohort [TVC]) and 61.0% (11.8–84.2) and 73.9% (1.1–95.3) in women naïve to HPV infection at baseline (TVC-naïve), respectively. The high VE observed in Japanese women, accompanied by a sustained immune response and a clinically acceptable safety profile, support findings of large, international trials. PMID:25424783

Penile Analogue of Stratified Mucin-Producing Intraepithelial Lesion of the Cervix: The First Described Case. A Diagnostic Pitfall.

PubMed

Michal, Michael; Michal, Michal; Miesbauerova, Marketa; Hercogova, Jana; Skopalikova, Barbora; Kazakov, Dmitry V

2016-05-01

The authors report a case where undifferentiated (classic) penile intraepithelial neoplasia was associated with the presence of goblet cells throughout the full epithelial thickness and which later progressed into an invasive carcinoma. The lesion evolved in three consecutive biopsies from only surface epithelium occupying numerous goblet cells in the first to variably sized solid nodules in the dermis composed of atypical squamous and/or basaloid cells intermixed with numerous goblet cells in the third biopsy. Both cellular components expressed CK7 and p16 protein. Human Papillomavirus (HPV) genotyping revealed high risk HPV type 16. To the best of our knowledge, this is the first description of such a lesion occurring on the penis, which can be considered the penile analogue of cervical stratified mucin-producing intraepithelial lesion (SMILE). The correct diagnosis was rendered retrospectively, after recognition of the existence of a vulvar lesion resembling cervical SMILE. The initial biopsy was misinterpreted as extramammary Paget disease, which also constitutes the main pitfall in the differential diagnosis. Another important differential diagnosis is penile/vulvar mucinous metaplasia. The finding of atypical squamous epithelial cells positive for p16 associated with mucinous cells present throughout the full epithelial thickness is a clue to the diagnosis of penile SMILE.

Fluorescence spectroscopy for diagnostic differentiation in uteri's cervix biopsies with cervical/vaginal atypical cytology.

PubMed

Rodero, Ademir Barianni; Silveira, Landulfo; Rodero, David Augusto; Racanicchi, Roberto; Pacheco, Marcos Tadeu T

2008-09-01

This work aims the diagnostic differentiation of chronic inflammation (CC), low-grade Intraepithelial squamous lesions (LGSIL) and high-grade intraepithelial squamous lesions (HGSIL) in biopsies of cervix of uterus from patients with atypias (ASC-US and ASC-H) and lesions (LGSIL and HGSIL), traced in the cervical/vaginal cytology by using Laser-Induced Fluorescence Spectroscopy (LIFS), with 488 nm excitation wavelength. Ninety seven biopsies from 32 patients with atypical cervical/vaginal cytology were collected. The biopsies were guided by colposcopy and taken at the squamous-columnar junction. Fluorescence emission spectra of each biopsy were collected by means of an optical fiber cable coupled to an argon laser at 488 nm as excitation source and addressed to a spectrograph and CCD camera/controller. Spectra were separated into three groups, CC, LGSIL and HGSIL, based on the cytopathology. It was detected similar mean spectra profiles for CC and LGSIL, and differences for HGSIL. An algorithm was developed for tissue classification based on the intensity of the multiplication of each spectrum by the mean spectrum of each group, searching for a discriminator that would address this spectral difference. The sensitivity and specificity of HGSIL identification, compared to CC and LGSIL was 89% and 100%, respectively. The LIFS using excitation wavelength of 488 nm could be used to differentiate HGSIL lesions from LGSIL and CC inflammation, and could help a precocious and less invasive diagnosis of cervix lesions.

Repeat Prostate Biopsy Practice Patterns in a Statewide Quality Improvement Collaborative.

PubMed

Burks, Frank N; Hu, Jonathan C; Telang, Dinesh; Liu, Alice; Hawken, Scott; Montgomery, Zack; Linsell, Susan; Montie, James E; Miller, David C; Ghani, Khurshid R

2017-08-01

We examined rebiopsies in MUSIC (Michigan Urological Surgery Improvement Collaborative) to understand adherence to guidelines recommending repeat prostate biopsy in patients with multifocal high grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. We analyzed data on men undergoing repeat biopsy, practice patterns and cancer detection rates. Multivariate regression modeling was used to calculate the proportion of patients undergoing rebiopsy. We used claims data to validate the treatment classification in MUSIC. To understand reasons for not performing rebiopsy we reviewed records of a sample of patients with atypical small acinar proliferation. We identified 5,375 men with a negative biopsy, of whom 411 (7.6%) underwent repeat biopsy. In 718 men with high grade prostatic intraepithelial neoplasia, 350 with atypical small acinar proliferation and 587 with high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation or atypical small acinar proliferation alone at initial biopsy the rebiopsy rate was 20.7%, 42.5% and 55.6%, respectively. The adjusted proportion of patients with rebiopsy in each practice ranged from 0% to 17.2% (p <0.001). The overall cancer detection rate at rebiopsy was 39.3%. It was highest after atypical small acinar proliferation (adjusted probability 0.39, 95% CI 0.30-0.48), and after high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation (adjusted probability 0.50, 95% CI 0.35-0.65). The greatest Gleason 7 or greatest detection rate of 41.1% was found in patients with high grade prostatic intraepithelial neoplasia and atypical small acinar proliferation. Chart review revealed that 45.5% of patients with atypical small acinar proliferation underwent prostate specific antigen testing instead of rebiopsy while 36% failed to undergo rebiopsy despite a recommendation. Rebiopsy rates vary in Michigan practices with relatively low use in men with high grade

Evaluation of DNA Single and Double Strand Breaks in Women with Cervical Neoplasia Based on Alkaline and Neutral Comet Assay Techniques

PubMed Central

Cortés-Gutiérrez, Elva I.; Hernández-Garza, Fernando; García-Pérez, Jorge O.; Dávila-Rodríguez, Martha I.; Aguado-Barrera, Miguel E.; Cerda-Flores, Ricardo M.

2012-01-01

A hospital-based unmatched case-control study was performed in order to determine the relation of DNA single (ssb) and double (dsb) strand breaks in women with and without cervical neoplasia. Cervical epithelial cells of 30 women: 10 with low grade squamous intraepithelial lesions (LG-SIL), 10 with high-grade SIL (HG-SIL), and 10 without cervical lesions were evaluated using alkaline and neutral comet assays. A significant increase in global DNA damage (ssb + dsb) and dsb was observed in patients with HG-SIL (48.90 ± 12.87 and 23.50 ± 13.91), patients with LG-SIL (33.60 ± 14.96 and 11.20 ± 5.71), and controls (21.70 ± 11.87 and 5.30 ± 5.38; resp.). Pearson correlation coefficient reveled a strong relation between the levels ssb and dsb (r2 = 0.99, P = 0.03, and r2 = 0.94, P = 0.16, resp.) and progression of neoplasia. The increase of dsb damage in patients with HG-SIL was confirmed by DNA breakage detection-FISH (DBD-FISH) on neutral comets. Our results argue in favor of a real genomic instability in women with cervical neoplasia, which was strengthened by our finding of a higher proportion of DNA dsb. PMID:23093842

Pain relief for women with cervical intraepithelial neoplasia undergoing colposcopy treatment.

PubMed

Gajjar, Ketan; Martin-Hirsch, Pierre P L; Bryant, Andrew; Owens, Gemma L

2016-07-18

Pre-cancerous lesions of cervix (cervical intraepithelial neoplasia (CIN)) are usually treated with excisional or ablative procedures. In the UK, the National Health Service (NHS) cervical screening guidelines suggest that over 80% of treatments should be performed in an outpatient setting (colposcopy clinics). Furthermore, these guidelines suggest that analgesia should always be given prior to laser or excisional treatments. Currently various pain relief strategies are employed that may reduce pain during these procedures. To assess whether the administration of pain relief (analgesia) reduces pain during colposcopy treatment and in the postoperative period. We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 2), MEDLINE (1950 to March week 3, 2016) and Embase (1980 to week 12, 2016) for studies of any design relating to analgesia for colposcopic management. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Randomised controlled trials (RCTs) that compared all types of pain relief before, during or after outpatient treatment to the cervix, in women with CIN undergoing loop excision, laser ablation, laser excision or cryosurgery in an outpatient colposcopy clinic setting. We independently assessed study eligibility, extracted data and assessed risk of bias. We entered data into Review Manager 5 and double checked it for accuracy. Where possible, we expressed results as mean pain score and standard error of the mean with 95% confidence intervals (CI) and synthesised data in a meta-analysis. We included 19 RCTs (1720 women) of varying methodological quality in the review. These trials compared a variety of interventions aimed at reducing pain in women who underwent treatment for CIN, including cervical injection with lignocaine alone, lignocaine with adrenaline, buffered lignocaine with adrenaline, prilocaine with felypressin, oral

Estimates of the timing of reductions in genital warts and high grade cervical intraepithelial neoplasia after onset of human papillomavirus (HPV) vaccination in the United States.

PubMed

Chesson, Harrell W; Ekwueme, Donatus U; Saraiya, Mona; Dunne, Eileen F; Markowitz, Lauri E

2013-08-20

The objective of this study was to estimate the number of years after onset of a quadrivalent HPV vaccination program before notable reductions in genital warts and cervical intraepithelial neoplasia (CIN) will occur in teenagers and young adults in the United States. We applied a previously published model of HPV vaccination in the United States and focused on the timing of reductions in genital warts among both sexes and reductions in CIN 2/3 among females. Using different coverage scenarios, the lowest being consistent with current 3-dose coverage in the United States, we estimated the number of years before reductions of 10%, 25%, and 50% would be observed after onset of an HPV vaccination program for ages 12-26 years. The model suggested female-only HPV vaccination in the intermediate coverage scenario will result in a 10% reduction in genital warts within 2-4 years for females aged 15-19 years and a 10% reduction in CIN 2/3 among females aged 20-29 years within 7-11 years. Coverage had a major impact on when reductions would be observed. For example, in the higher coverage scenario a 25% reduction in CIN2/3 would be observed with 8 years compared with 15 years in the lower coverage scenario. Our model provides estimates of the potential timing and magnitude of the impact of HPV vaccination on genital warts and CIN 2/3 at the population level in the United States. Notable, population-level impacts of HPV vaccination on genital warts and CIN 2/3 can occur within a few years after onset of vaccination, particularly among younger age groups. Our results are generally consistent with early reports of declines in genital warts among youth. Published by Elsevier Ltd.

High-dose-rate Intracavitary Radiotherapy in the Management of Cervical Intraepithelial Neoplasia 3 and Carcinoma In Situ Presenting With Poor Histologic Factors After Undergoing Excisional Procedures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Yong Bae, E-mail: ybkim3@yuhs.ac; Kim, Young Tae; Cho, Nam Hoon

2012-09-01

Purpose: To assess the effectiveness of high-dose-rate intracavitary radiotherapy (HDR-ICR) in patients with cervical intraepithelial neoplasia 3 (CIN 3) and carcinoma in situ (CIS) presenting with poor histologic factors for predicting residual disease after undergoing diagnostic excisional procedures. Methods and Materials: This study was a retrospective analysis of 166 patients with CIN 3 (n=15) and CIS (n=151) between October 1986 and December 2005. They were diagnosed by conization (n=158) and punch biopsy (n=8). Pathologic analysis showed 135 cases of endocervical gland involvement (81.4%), 74 cases of positive resection margins (44.5%), and 52 cases of malignant cells on endocervical curettage (31.3%).more » All patients were treated with HDR-ICR using Co{sup 60} or Ir{sup 192} at a cancer center. The dose was prescribed at point A located 2 cm superior to the external os and 2 cm lateral to the axis of the tandem for intact uterus. Results: Median age was 61 years (range, 29-77). The median total dose of HDR-ICR was 30 Gy/6 fractions (range, 30-52). At follow-up (median, 152 months), 2 patients developed recurrent diseases: 1 CIN 2 and 1 invasive carcinoma. One hundred and forty patients survived and 26 patients died, owing to nonmalignant intercurrent disease. Rectal bleeding occurred in one patient; however, this symptom subsided with conservative management. Conclusions: Our data showed HDR-ICR is an effective modality for CIN 3 and CIS patients presenting with poor histologic factors after excisional procedures. HDR-ICR should be considered as a definitive treatment in CIN 3 and CIS patients with possible residual disease after undergoing excisional procedures.« less

A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women.

PubMed

Joura, Elmar A; Giuliano, Anna R; Iversen, Ole-Erik; Bouchard, Celine; Mao, Constance; Mehlsen, Jesper; Moreira, Edson D; Ngan, Yuen; Petersen, Lone Kjeld; Lazcano-Ponce, Eduardo; Pitisuttithum, Punnee; Restrepo, Jaime Alberto; Stuart, Gavin; Woelber, Linn; Yang, Yuh Cheng; Cuzick, Jack; Garland, Suzanne M; Huh, Warner; Kjaer, Susanne K; Bautista, Oliver M; Chan, Ivan S F; Chen, Joshua; Gesser, Richard; Moeller, Erin; Ritter, Michael; Vuocolo, Scott; Luxembourg, Alain

2015-02-19

The investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age. We performed a randomized, international, double-blind, phase 2b-3 study of the 9vHPV vaccine in 14,215 women. Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6. Serum was collected for analysis of antibody responses. Swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue were obtained and used for HPV DNA testing, and liquid-based cytologic testing (Papanicolaou testing) was performed regularly. Tissue obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and conization) was tested for HPV. The rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9vHPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1000 person-years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to HPV-31, 33, 45, 52, and 58 in a prespecified per-protocol efficacy population (susceptible population) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group (efficacy of the 9vHPV vaccine, 96.7%; 95% confidence interval, 80.9 to 99.8). Antibody responses to HPV-6, 11, 16, and 18 were noninferior to those generated by the qHPV vaccine. Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group. The 9vHPV vaccine prevented infection and disease

Aberrant Expression of the Cell Polarity Regulator aPKCλ/ι is Associated With Disease Progression in Cervical Intraepithelial Neoplasia (CIN): A Possible Marker for Predicting CIN Prognosis.

PubMed

Mizushima, Taichi; Asai-Sato, Mikiko; Akimoto, Kazunori; Nagashima, Yoji; Taguri, Masataka; Sasaki, Kazunori; Nakaya, Masa-aki; Asano, Ryoko; Tokinaga, Aya; Kiyono, Tohru; Hirahara, Fumiki; Ohno, Shigeo; Miyagi, Etsuko

2016-03-01

Atypical protein kinase C λ/ι (aPKCλ/ι) is a regulator of epithelial cellular polarity. It is also overexpressed in several cancers and functions in cell proliferation and invasion. Therefore, we hypothesized that aPKCλ/ι may be involved in development and progression of cervical intraepithelial neoplasia (CIN), the precancerous disease of cervical cancer induced by human papillomavirus. To do this, we investigated the relationship between aPKCλ/ι expression and CIN. aPKCλ/ι expression level and subcellular localization were assessed in 192 CIN biopsy samples and 13 normal epithelial samples using immunohistochemistry. aPKCλ/ι overexpression (normal epithelium, 7.7%; CIN1, 41.7%; CIN2/3, 76.4%) and aPKCλ/ι nuclear localization (normal epithelium, 0.0%; CIN1, 36.9%; CIN2/3, 78.7%) were higher in CIN samples than normal samples (P<0.05), suggesting that CIN grade is related to aPKCλ/ι overexpression and nuclear localization. Then, 140 CIN cases were retrospectively analyzed for 4-yr cumulative disease progression and regression rates using the Cox proportional hazards model. CIN1 cases with aPKCλ/ι overexpression or aPKCλ/ι nuclear localization had a higher progression rate than CIN1 cases with normal aPKCλ/ι expression levels or cytoplasmic localization (62.5% vs. 9.7% and 63.1% vs. 9.4%, respectively; P<0.001). Multivariate analysis indicated that human papillomavirus types 16 and 18, aPKCλ/ι overexpression (hazard ratio=4.26; 95% confidence interval, 1.50-12.1; P=0.007), and aPKCλ/ι nuclear localization (hazard ratio=3.59; 95% confidence interval, 1.24-10.4; P=0.019) were independent risk factors for CIN1 progression. In conclusion, aPKCλ/ι could be useful for the therapeutic management of patients with CIN, particularly those with non-human papillomavirus 16/18 types.

GLUT-1 expression in pancreatic neoplasia: implications in pathogenesis, diagnosis, and prognosis.

PubMed

Basturk, Olca; Singh, Rajendra; Kaygusuz, Ecmel; Balci, Serdar; Dursun, Nevra; Culhaci, Nil; Adsay, N Volkan

2011-03-01

GLUT-1 has been found to have an important role in the upregulation of various cellular pathways and implicated in neoplastic transformation correlating with biological behavior in malignancies. However, literature regarding the significance of GLUT-1 expression in pancreatic neoplasia has been limited and controversial. Immunohistochemical expression of GLUT-1 was tested in a variety of pancreatic neoplasia including ductal adenocarcinomas (DAs), pancreatic intraepithelial neoplasms (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and serous cystadenomas. There was a progressive increase in the expression of GLUT-1 from low- to higher-grade dysplastic lesions: All higher-grade PanINs/IPMNs (the ones with moderate/high-grade dysplasia) revealed noticeable GLUT-1 expression. Among the 94 DAs analyzed, there were minimal/moderate expression in 46 and significant expression in 24 DAs. However, all 4 clear-cell variants of DAs revealed significant GLUT-1 immunolabeling, as did areas of clear-cell change seen in other DAs. Moreover, all 12 serous cystadenomas expressed significant GLUT-1. GLUT-1 expression was also directly correlated with DA histological grade (P = 0.016) and tumor size (P = 0.03). GLUT-1 may give rise to the distinctive clear-cell appearance of these tumors by inducing the accumulation of glycogen in the cytoplasm. Additionally, because GLUT-1 expression was related to histological grade and tumor size of DA, further studies are warranted to investigate the association of GLUT-1 with prognosis and tumor progression.

Cytological surveillance compared with immediate referral for colposcopy in management of women with low grade cervical abnormalities: multicentre randomised controlled trial.

PubMed

2009-07-28

To examine the effectiveness of cytological surveillance in primary care compared with immediate referral for colposcopic examination in women with low grade abnormal results on cervical cytology tests. Multicentre individually randomised controlled trial. NHS cervical screening programmes in Grampian, Tayside, and Nottingham. 4439 women, aged 20-59, with a cytology result showing borderline nuclear abnormalities or mild dyskaryosis, October 1999-October 2002. Cytological screening every six months in primary care (n=2223) or referral for colposcopy and related interventions (n=2216). All women were followed for three years, concluding with an exit appointment at which colposcopic examination was undertaken. Colposcopists assessing outcome at this appointment were blinded to randomisation. Primary end point: cumulative incidence of cervical intraepithelial neoplasia grade II or more severe disease. Other end points: cervical intraepithelial neoplasia grade III or worse, clinically significant anxiety and depression, other self reported after effects, and rates of non-attendance. Analysis was by intention to treat; all those randomised were included. The cumulative incidence of cervical intraepithelial neoplasia grade II or worse was 79 per 1000 person years in the colposcopy arm and 58 per 1000 person years in the cytological surveillance arm (relative risk 1.37, 95% confidence interval 1.19 to 1.57). This difference was less marked for cervical intraepithelial neoplasia grade III or more severe disease, but the incidence was still higher in the colposcopy arm (relative risk 1.26, 1.04 to 1.53). Among women randomised to immediate colposcopy, 79% (74.9% to 82.5%) of cases of cervical intraepithelial neoplasia grade II or worse were diagnosed at the time of the immediate colposcopy, while among women randomised to cytological surveillance, 77% (72.1% to 81.2%) of cases were detected by surveillance cytology and related interventions. Similar proportions of women

Young women, cervical intraepithelial neoplasia and human papillomavirus: risk factors for persistence and recurrence.

PubMed

Frega, Antonio; Stentella, Patrizia; De Ioris, Andrea; Piazze, Juan Josè; Fambrini, Massimiliano; Marchionni, Mauro; Cosmi, Ermelando Vinicio

2003-07-10

Human papillomavirus (HPV) infection is one of the most common sexually transmitted infections (STIs) in young women. They can occur in one or multiple areas of the female genitalia. Usually, the vulva is the initial site of implantation for HPV. The purpose of our study is to evaluate the epidemiological aspects, incidence of single or multiple lesions in the lower genital tract, correlation between sexual behaviour and their localization and behaviour risk factors for persistence and recurrence of HPV lesions and cervical intraepithelial lesion (CIN) in a long-term follow-up among young women. We recruited 268 patients aged 11-21 years who previously had cytology and/or physical examination suspicious for HPV infection. The women were interviewed and asked information about lifestyle, sexual behaviour, work, personal or family history of genital warts and school attendance. We considered individuals to be 'smokers' if they smoked more than five cigarettes/day. No specific data were recorded about oral contraception, nevertheless, no woman had used oral contraceptives (OCs) for more than 2 years. Young women included in the study were between the age of 12 and 21 years who had HVP lesions after entry examinations and had undergone no treatment for HPV lesions prior to entry. Other exclusion criteria relevant to this study included cervical excisional treatment prior to entry or later. Two hundred and thirty-four young women were included in our study group. Our diagnostic schedule for a complete evaluation included exo- and endocervical cytology, colposcopy, directed biopsy and microcolpohysteroscopy. The treatment was performed with a LASER CO2 Coherent 400, model 451, with Zeiss photocolposcopy attachment. The finding that, among 126/234 (53.8%) adolescents using contraceptives, only 85 (36.3%) have used condom, the only barrier form of contraceptive effectively protecting against virus, shows a low awareness of the high risk for contracting HPV infection among

Cryotherapy Reduces Progression of Cervical Intraepithelial Neoplasia Grade 1 in South African HIV-Infected Women: A Randomized, Controlled Trial.

PubMed

Firnhaber, Cynthia; Swarts, Avril; Goeieman, Bridgette; Rakhombe, Ntombi; Mulongo, Masangu; Williamson, Anna-Lise; Michelow, Pam; Ramotshela, Sibongile; Faesen, Mark; Levin, Simon; Wilkin, Timothy

2017-12-15

HIV-infected women are at an increased risk of cervical cancer, especially in resource-limited countries. Cervical cancer prevention strategies focus treating cervical high-grade squamous intraepithelial lesions (HSIL). The management of low-grade squamous intraepithelial lesions (LSIL) in HIV-infected women is unknown. HIV treatment clinic in Johannesburg, South Africa. We randomized HIV-infected women with histologic cervical LSIL to cervical cryotherapy vs. no treatment (standard of care). Cervical high-risk human papillomavirus testing (hrHPV) was performed at baseline. All women underwent cervical cytology and colposcopic biopsies 12 months after enrollment. The primary end point was HSIL on histology at month 12. Chi-square was used to compare arms. Overall, 220 HIV-infected women were randomized to cryotherapy (n = 112) or no treatment (n = 108). Median age was 38 years, 94% were receiving antiretroviral therapy; median CD4 was 499 cells per cubic millimeter, and 59% were hrHPV positive. Cryotherapy reduced progression to HSIL: 2/99 (2%) in the cryotherapy arm and 15/103 (15%) in the no treatment arm developed HSIL, 86% reduction (95% confidence interval: 41% to 97%; P = 0.002). Among 17 HSIL end points, 16 were hrHPV+ at baseline. When restricting the analysis to hrHPV+ women, HSIL occurred in 2/61 (3%) in the cryotherapy arm vs. 14/54 (26%) in the no treatment arm, 87% reduction (95% confidence interval: 47% to 97%; P = 0.0004). Participants in the cryotherapy arm experienced greater regression to normal histology and improved cytologic outcomes. Treatment of cervical LSIL with cryotherapy decreased progression to HSIL among HIV-infected women especially if hrHPV positive. These results support treatment of LSIL in human papillomavirus test-and-treat approaches for cervical cancer prevention in resource-constrained settings.

Human papillomavirus type 16 variants in cervical intraepithelial neoplasia and invasive carcinoma in San Luis Potosí City, Mexico

PubMed Central

López-Revilla, Rubén; Pineda, Marco A; Ortiz-Valdez, Julio; Sánchez-Garza, Mireya; Riego, Lina

2009-01-01

Background In San Luis Potosí City cervical infection by human papillomavirus type 16 (HPV16) associated to dysplastic lesions is more prevalent in younger women. In this work HPV16 subtypes and variants associated to low-grade intraepithelial lesions (LSIL), high-grade intraepithelial lesions (HSIL) and invasive cervical cancer (ICC) of 38 women residing in San Luis Potosí City were identified by comparing their E6 open reading frame sequences. Results Three European (E) variants (E-P, n = 27; E-T350G, n = 7; E-C188G, n = 2) and one AA-a variant (n = 2) were identified among the 38 HPV16 sequences analyzed. E-P variant sequences contained 23 single nucleotide changes, two of which (A334G, A404T) had not been described before and allowed the phylogenetic separation from the other variants. E-P A334G sequences were the most prevalent (22 cases, 57.9%), followed by the E-P Ref prototype (8 cases, 21.1%) and E-P A404T (1 case, 2.6%) sequences. The HSIL + ICC fraction was 0.21 for the E-P A334G variants and 0.00 for the E-P Ref variants. Conclusion We conclude that in the women included in this study the HPV16 E subtype is 19 times more frequent than the AA subtype; that the circulating E variants are E-P (71.1%) > E-T350G (18.4%) > E-C188G (5.3%); that 71.0% of the E-P sequences carry the A334G single nucleotide change and appear to correspond to a HPV16 variant characteristic of San Luis Potosi City more oncogenic than the E-P Ref prototype. PMID:19216802

Can human papillomavirus DNA testing of self-collected vaginal samples compare with physician-collected cervical samples and cytology for cervical cancer screening in developing countries?

PubMed Central

Bhatla, Neerja; Dar, Lalit; Patro, A. Rajkumar; Kumar, Pankaj; Kriplani, Alka; Gulati, Arti; Iyer, Venkateswaran K.; Mathur, Sandeep R.; Sreenivas, Vishnubhatla; Shah, Keerti V.; Gravitt, Patti E.

2013-01-01

Background To determine human papillomavirus (HPV) types by polymerase chain reaction (PCR)-reverse line blot assay and examine the concordance between HPV by Hybrid Capture 2 (HC2) and PCR on self-collected vaginal and physician-collected cervical samples and cytology. Methods This was a cross-sectional study of 546 sexually active women aged ≥30 years with persistent vaginal discharge, intermenstrual or postcoital bleeding or an unhealthy cervix. Participants self-collected vaginal samples (HPV-S) and physicians collected cervical samples for conventional Pap smear and HPV DNA (HPV-P) testing and performed colposcopy, with directed biopsy, if indicated. HPV testing and genotyping was done by HC2 and PCR reverse line blot assay. Concordance between HC2 and PCR results of self- and physician-collected samples was determined using a Kappa statistic (κ) and Chi-square test. Results Complete data were available for 512 sets with 98% of women providing a satisfactory self-sample. PCR detected oncogenic HPV in 12.3% of self- and 13.0% of physician-collected samples. Overall, there was 93.8% agreement between physician-collected and self-samples (κ = 76.31%, 95% confidence interval [CI]: 64.97–82.29%, p = 0.04)—complete concordance in 473 cases (57 positive, 416 negative), partial concordance in seven pairs and discordance in 32 pairs. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of self-sampling for detection of cervical intraepithelial neoplasia (CIN)2+ disease were 82.5%, 93.6%, 52.4% and 98.4%, respectively; for physician-sampling they were 87.5%, 93.2%, 52.2% and 98.9%, respectively; and for cytology they were 77.5%, 87.3%, 34.1% and 97.9%, respectively. Concordance between HC2 and PCR was 90.9% for self-samples (κ = 63.7%, 95% CI: 55.2–72.2%) and 95.3% for physician-collected samples (κ = 80.4%, 95% CI: 71.8–89.0%). Conclusions Self-HPV sampling compares favourably with physician-sampling and

A Non–Gas-Based Cryotherapy System for the Treatment of Cervical Intraepithelial Neoplasia: A Mixed-Methods Approach for Initial Development and Testing

PubMed Central

Cremer, Miriam; Paul, Proma; Bergman, Katie; Haas, Michael; Maza, Mauricio; Zevallos, Albert; Ossandon, Miguel; Garai, Jillian D; Winkler, Jennifer L

2017-01-01

ABSTRACT Background: Gas-based cryotherapy is the most widely used treatment strategy for cervical intraepithelial neoplasia (CIN) in low-resource settings, but reliance on gas presents challenges in low- and middle-income countries (LMICs). Our team adapted the original CryoPen Cryosurgical System, a cryotherapy device that does not require compressed gas and is powered by electricity, for use in LMICs. Methods: A mixed-methods approach was used involving both qualitative and quantitative methods. First, we used a user-centered design approach to identify priority features of the adapted device. U.S.-based and global potential users of the adapted CryoPen participated in discussion groups and a card sorting activity to rank 7 features of the adapted CryoPen: cost, durability, efficacy and safety, maintenance, no need for electricity, patient throughput, and portability. Mean and median rankings, overall rankings, and summary rankings by discussion group were generated. In addition, results of several quantitative tests were analyzed including bench testing to determine tip temperature and heat extraction capabilities; a pathology review of CIN grade 3 cases (N=107) to determine target depth of necrosis needed to achieve high efficacy; and a pilot study (N=5) investigating depth of necrosis achieved with the adapted device to assess efficacy. Results: Discussion groups revealed 4 priority themes for device development in addition to the need to ensure high efficacy and safety and low cost: improved portability, durability, ease of use, and potential for cure. Adaptions to the original CryoPen system included a single-core, single-tip model; rugged carrying case; custom circuit to allow car battery charging; and sterilization by high-level disinfection. In bench testing, there were no significant differences in tip temperature or heat extraction capability between the adapted CryoPen and the standard cryotherapy device. In 80% of the cases in the pilot study, the

A Non-Gas-Based Cryotherapy System for the Treatment of Cervical Intraepithelial Neoplasia: A Mixed-Methods Approach for Initial Development and Testing.

PubMed

Cremer, Miriam; Paul, Proma; Bergman, Katie; Haas, Michael; Maza, Mauricio; Zevallos, Albert; Ossandon, Miguel; Garai, Jillian D; Winkler, Jennifer L

2017-03-24

Gas-based cryotherapy is the most widely used treatment strategy for cervical intraepithelial neoplasia (CIN) in low-resource settings, but reliance on gas presents challenges in low- and middle-income countries (LMICs). Our team adapted the original CryoPen Cryosurgical System, a cryotherapy device that does not require compressed gas and is powered by electricity, for use in LMICs. A mixed-methods approach was used involving both qualitative and quantitative methods. First, we used a user-centered design approach to identify priority features of the adapted device. U.S.-based and global potential users of the adapted CryoPen participated in discussion groups and a card sorting activity to rank 7 features of the adapted CryoPen: cost, durability, efficacy and safety, maintenance, no need for electricity, patient throughput, and portability. Mean and median rankings, overall rankings, and summary rankings by discussion group were generated. In addition, results of several quantitative tests were analyzed including bench testing to determine tip temperature and heat extraction capabilities; a pathology review of CIN grade 3 cases (N=107) to determine target depth of necrosis needed to achieve high efficacy; and a pilot study (N=5) investigating depth of necrosis achieved with the adapted device to assess efficacy. Discussion groups revealed 4 priority themes for device development in addition to the need to ensure high efficacy and safety and low cost: improved portability, durability, ease of use, and potential for cure. Adaptions to the original CryoPen system included a single-core, single-tip model; rugged carrying case; custom circuit to allow car battery charging; and sterilization by high-level disinfection. In bench testing, there were no significant differences in tip temperature or heat extraction capability between the adapted CryoPen and the standard cryotherapy device. In 80% of the cases in the pilot study, the adapted CryoPen achieved the target depth

Intraepithelial G3 adenocarcinoma of the endometrium after tamoxifen treatment.

PubMed

Marchesoni, Diego; Driul, L; Mozzanega, B; Nardelli, G B; Parenti, A

2005-01-01

In this paper we describe a case of endometrial carcinoma observed in a post-menopausal patient who was treated with tamoxifen for 5 years after a mastectomy for cancer. She came to our department because of vaginal bleeding 2 years after the end of tamoxifen treatment. She underwent hysteroscopy and a D and C. A polypoid endometrium completely filled the uterine cavity and was carefully removed by curettage; histology showed a highly undifferentiated neoplasia with a component of serous adenocarcinoma, which was likely to originate from endometrial polyps. The patient underwent radical hysterectomy, but no residual tumor was found in the uterus or in the tubes, ovary, or pelvic nodes, in spite of its low differentiation grade and high potential aggressiveness, and even though the patient was already symptomatic. Two years after surgery the patient is disease free, which is consistent with the evaluation of the surgical specimen, but unusual in poorly differentiated neoplasms.

Is atypical squamous cells that cannot exclude high-grade squamous intraepithelial lesion clinically significant?

PubMed

McHale, Michael T; Souther, Jessica; Elkas, John C; Monk, Bradley J; Harrison, Terry A

2007-04-01

To determine the cumulative risk of cervical intraepithelial neoplasia (CIN) 2 or 3 in patients with atypical squamous cells, cannot exclude HSIL (ASC-H). A retrospective analysis was performed to identify patients referred to the dysplasia clinic with ASC-H. Initial evaluation included colposcopy, endocervical curettage, and an ectocervical biopsy, when indicated, in all the patients. A follow-up evaluation was performed at 6 and 12 months. Cumulative histological diagnosis of CIN 2 or 3 at 12 months served as the clinical end point. Two hundred twenty-nine patients with ASC-H and with a mean age of 32.8 years were evaluated. At the time of initial colposcopy, only 10.0% (23/229; 95% CI = 6.5%-15%) of the patients had histological evidence of CIN 2 or 3. The cumulative risk of CIN 2 or 3 was 12.2% (95% CI = 8%-17%). Evaluation of patients with ASC-H with colposcopy does lead to the detection of CIN 2 or 3 but perhaps at a rate lower than previously reported.

Perceived Health-Related Quality of Life in Women With Vulvar Neoplasia: A Cross Sectional Study.

PubMed

Kobleder, Andrea; Nikolic, Nataša; Hechinger, Mareike; Denhaerynck, Kris; Hampl, Monika; Mueller, Michael D; Senn, Beate

2016-09-01

The aim of the study was to determine health-related quality of life (HRQoL) of women with surgically treated vulvar intraepithelial neoplasia (VIN) and vulvar cancer (VC) during the first week after hospital discharge. Further objectives were to investigate differences between women with VIN and VC as well as to examine whether correlations exist between women's symptom experience and HRQoL. This cross-sectional study was conducted in 8 hospitals in Germany and Switzerland. Women with VIN and VC rated HRQoL with the validated German Short-Form 36. Differences between HRQoL in women with VIN and VC were tested with Wilcoxon rank-sum score. The WOMen with vulvAr Neoplasia (WOMAN) - Patient reported Outcome (PRO) self-report instrument was used to measure women's symptom experience. Correlations between symptoms and HRQoL were calculated using Spearman correlation coefficient. Women with VIN and VC (n = 65) reported lower HRQoL in physical aspects (Physical Component Summary [PCS], 34.9) than that in mental aspects (Mental Component Summary, 40.5). Women with VC had lower HRQoL than women with VIN, as manifested by significant differences concerning the dimensions of "physical functioning" and "role-physical." "Difficulties in daily life" as a distressing symptom correlated with MCS and PCS. Wound-related symptoms correlated with PCS and psychosocial symptoms/issues with MCS. Analysis showed that women with vulvar neoplasia reported lower HRQoL in the physical and mental dimensions 1 week after discharge than comparable studies referring to months or years after surgery. Health-related quality of life is influenced by physical impairment because physical symptoms are prevalent 1 week after discharge. Patient education should focus on symptom management in an early postsurgical phase to enhance women's HRQoL.

Newly developed vaginal atrophy symptoms II and vaginal pH: a better correlation in vaginal atrophy?

PubMed

Tuntiviriyapun, P; Panyakhamlerd, K; Triratanachat, S; Chatsuwan, T; Chaikittisilpa, S; Jaisamrarn, U; Taechakraichana, N

2015-04-01

The primary objective of this study was to evaluate the correlation among symptoms, signs, and the number of lactobacilli in postmenopausal vaginal atrophy. The secondary objective was to develop a new parameter to improve the correlation. A cross-sectional descriptive study. Naturally postmenopausal women aged 45-70 years with at least one clinical symptom of vaginal atrophy of moderate to severe intensity were included in this study. All of the objective parameters (vaginal atrophy score, vaginal pH, the number of lactobacilli, vaginal maturation index, and vaginal maturation value) were evaluated and correlated with vaginal atrophy symptoms. A new parameter of vaginal atrophy, vaginal atrophy symptoms II, was developed and consists of the two most bothersome symptoms (vaginal dryness and dyspareunia). Vaginal atrophy symptoms II was analyzed for correlation with the objective parameters. A total of 132 naturally postmenopausal women were recruited for analysis. Vaginal pH was the only objective parameter found to have a weak correlation with vaginal atrophy symptoms (r = 0.273, p = 0.002). The newly developed vaginal atrophy symptoms II parameter showed moderate correlation with vaginal pH (r = 0.356, p < 0.001) and a weak correlation with the vaginal atrophy score (r = 0.230, p < 0.001). History of sexual intercourse within 3 months was associated with a better correlation between vaginal atrophy symptoms and the objective parameters. Vaginal pH was significantly correlated with vaginal atrophy symptoms. The newly developed vaginal atrophy symptoms II was associated with a better correlation. The vaginal atrophy symptoms II and vaginal pH may be better tools for clinical evaluation and future study of the vaginal ecosystem.

Sexually transmitted agents and cervical neoplasia in Colombia and Spain.

PubMed

de Sanjosé, S; Muñoz, N; Bosch, F X; Reimann, K; Pedersen, N S; Orfila, J; Ascunce, N; González, L C; Tafur, L; Gili, M

1994-02-01

Case-control studies of cervical intra-epithelial neoplasia grade III (CIN III) and of invasive cervical cancer were carried out in Spain and Colombia to assess the relationship between cervical cancer and 6 common sexually transmitted agents (STAs). The CIN-III studies included 525 cases and 512 controls matched for age and for the place of recruitment; the invasive-cancer studies included 373 histologically confirmed cases of squamous-cell carcinoma and 387 age-stratified controls selected randomly from the populations that generated the cases. Antibodies to Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, herpes simplex virus type II (HSV-2) and cytomegalovirus (CMV) were tested in 88% of the women. Cervical scrapes were examined for HPV DNA in 63% of the women using a polymerase-chain-reaction assay (PCR). Among controls, the highest antibody prevalence was to CMV (96.5%), followed by HSV-2 (31.4%) and C. trachomatis (23.3%). For all STAs, the sero-prevalence was markedly higher in Colombia than in Spain both for cases and for controls. After adjustment for the presence of HPV DNA, C. trachomatis was the only STA associated with CIN III in both countries; Spain and Colombia. In both countries, the risk of CIN III increased with increasing of C. trachomatis antibody titers. Among Spanish women, an increase in risk of invasive carcinoma was found for those with antibodies to N. gonorrhoeae; those with antibodies to HSV-2 and those with antibodies to C. trachomatis. These associations were present only in HPV-DNA-negative women. Among HPV-DNA-positive women, none of the STAs considered were associated with cervical neoplasia. Our findings could be interpreted as indicating that past infections with HSV-2, N. gonorrhoeae and C. trachomatis are surrogate markers of HPV, but because HPV DNA may have escaped detection, we cannot exclude that these STAs are also of separate etiological significance.

Vaginal disorders.

PubMed

Soderberg, S F

1986-05-01

Chronic vaginitis is the most common vaginal disorder. Dogs with vaginitis show no signs of systemic illness but often lick at the vulva and have purulent or hemorrhagic vaginal discharges. Vaginitis is most commonly secondary to a noninfectious inciting factor such as congenital vaginal anomalies, clitoral hypertrophy, foreign bodies, trauma to the vaginal mucosa, or vaginal tumors. Inspection of the caudal vagina and vestibule both visually and digitally will often reveal the source of vaginal irritation. Vaginal cytology is used to establish the stage of the estrous cycle as well as distinguish uterine from vaginal sources of discharge. Vaginal cultures are used to establish the predominant offending organism associated with vaginal discharges and may be used as a guide for selection of a therapeutic agent. Vaginitis is best managed by removing the inciting cause and treating the area locally with antiseptic douches. Congenital malformations at the vestibulovaginal or vestibulovulvar junction may prevent normal intromission. Affected bitches may be reluctant to breed naturally because of pain. Such defects are detected best by digital examination. Congenital vaginal defects may be corrected by digital or surgical means. Prolapse of tissue through the lips of the vulva may be caused by clitoral hypertrophy, vaginal hyperplasia, or vaginal tumors. Enlargement of clitoral tissue is the result of endogenous or exogenous sources of androgens. Treatment of this condition includes removal of the androgen source and/or surgical removal of clitoral tissue. Vaginal hyperplasia is detected during proestrus or estrus of young bitches. Hyperplastic tissue will regress during diestrus. Tissue that is excessively traumatized and/or prolapse of the entire vaginal circumference may be removed surgically. Ovariohysterectomy may be used to prevent recurrence. Vaginal tumors are detected most often in older intact bitches. Such tumors are generally of smooth muscle or fibrous

Risk of metachronous neoplasia on surveillance colonoscopy in young patients with colorectal neoplasia.

PubMed

Kim, Hyun Gun; Cho, Young-Seok; Cha, Jae Myung; Shin, Jeong Eun; Kim, Kyeong Ok; Yang, Hyo-Joon; Koo, Hoon Sup; Joo, Young-Eun; Boo, Sun-Jin

2018-03-01

Few prior reports exist that address the appropriate colonoscopy surveillance interval for individuals <50 years old. We compared the risk of metachronous neoplasia between younger (20-49 years) and older (50-54 years) cohorts. This multicenter retrospective cohort study compared the incidence of metachronous neoplasia in younger and older cohorts according to baseline risk stratification. Subjects were eligible if they underwent their first colonoscopy between June 2006 and May 2010 and had at least 1 or more surveillance colonoscopy up to June 2015. Among a total of 10,477 subjects who underwent baseline colonoscopy, 9722 were eligible after excluding 755 subjects. Of those 9722 subjects, 43% underwent surveillance colonoscopy. In the baseline high-risk adenoma group (n = 840), the 3-year risk of metachronous advanced neoplasia was 10.7% in the younger patients on screening colonoscopy and 8.9% in the older patients (P > .1). In the baseline low-risk adenoma group (n = 1869), the 5-year risk of metachronous advanced neoplasia was 4.9% in the younger patients on screening colonoscopy and 5.1% in the older patients (P > .1). Similarly, in the baseline no neoplasia group (n = 7013), the 5-year risk of metachronous advanced neoplasia was 4.1% in the younger patients on screening colonoscopy and 5.6% in the older patients (P > .1). Considering the similar risk of metachronous advanced neoplasia in younger and older individuals, we suggest a 3-year surveillance interval for high-risk adenoma and a 5-year surveillance interval for low-risk adenoma in young individuals without a strong family history. Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

A Review of Clinical Trials of Human Papillomavirus Prophylactic Vaccines

PubMed Central

Schiller, John T.; Castellsagué, Xavier; Garland, Suzanne M.

2015-01-01

End of study analyses of the phase III trials of prophylactic human papillomavirus (HPV) virus-like particle (VLP) vaccines in young women are now largely completed. Two distinct vaccines were evaluated, Gardasil® (Merck & Co., Whitehouse Station, NJ USA) a quadrivalent vaccine containing VLPs of types 6, 11, 16 and 18 and Cervarix® (GlaxoSmithKline Biologicals, Rixensart, Belgium), a bivalent vaccine containing VLPs of types 16 and 18. Both vaccines exhibited excellent safety and immunogenicity profiles. The vaccines also demonstrated remarkably high and similar efficacy against the vaccine-targeted types for a range of cervical endpoints from persistent infection to cervical intraepithelial neoplasia grade 3 (CIN3) in women naïve to the corresponding type at the time of vaccination. However, protection from incident infection or disease from non-vaccine types was restricted, and the vaccines had no effect on prevalent infection or disease. Gardasil® also demonstrated strong protection against genital warts and vulvar/vaginal neoplasia associated with the vaccine types. In other trials, Gardasil® protected mid-adult women from incident infection and CIN caused by the vaccine types and protected men for incident infection, genital warts and anal intraepithelial neoplasia by the vaccine types. Cervarix® protected against vaccine-targeted anal infections in women in an end of study evaluation. For practical reasons, efficacy studies have not been conducted in the primary target populations of current vaccination programs, adolescent girls and boys. However, immunogenicity bridging studies demonstrating excellent safety and strong immune responses in adolescence, coupled with the documentation of durable antibody responses and protection in young adults, leads to an optimistic projection of the effectiveness of the vaccines in adolescent vaccination programs. Taken together, the excellent clinical trial results strongly support the potential of the vaccines as

Is endoscopic forceps biopsy enough for a definitive diagnosis of gastric epithelial neoplasia?

PubMed

Lee, Chang Kyun; Chung, Il-Kwun; Lee, Suck-Ho; Kim, Sang Pil; Lee, Sae Hwan; Lee, Tae Hoon; Kim, Hong-Soo; Park, Sang-Heum; Kim, Sun-Joo; Lee, Ji-Hye; Cho, Hyun Deuk; Oh, Mee-Hye

2010-09-01

Endoscopic forceps biopsy (EFB) as the primary histological diagnosis of gastric epithelial neoplasia (GEN) is debated in the era of endoscopic resection (ER). Our aim was to investigate the diagnostic reliability of EFB in patients with GEN compared with ER specimens as the reference standard for the final diagnosis in a large consecutive series. This was a cross-sectional retrospective study at a tertiary-referral center. A total of 354 consecutive patients with 397 GENs underwent ER (endoscopic mucosal resection or endoscopic submucosal dissection). Discrepancy rates between the histological results from EFB and ER specimens were assessed. Discrepancies that could affect patient outcome or clinical care were considered major. The overall histological discrepancy rate between EFB and ER specimens was 44.5% (95% confidence interval [CI], 39.7-49.5%) among the enrolled patients. The overall discrepancy rate was significantly higher in the intraepithelial neoplasia (IEN) group than in the carcinoma group (49.8% vs 25.6%, P < 0.001). The major discrepancy rate was also significantly higher in the IEN group than in the carcinoma group (36.6% vs 7.0%, P < 0.001). In subgroup analysis of the IEN group, a major histological discrepancy rate of 33.6% (70/208) for low-grade and 42.7% (44/103) for high-grade IEN was found, respectively. Endoscopic forceps biopsy was insufficient for a definitive diagnosis and therapeutic planning in patients with GEN. ER should be considered as not only definitive treatment but also a procedure for a precise histological diagnosis for lesions initially assessed as GEN by forceps biopsy specimens.

Inhibition of Chronic Pancreatitis and Murine Pancreatic Intraepithelial Neoplasia by a Dual Inhibitor of c-RAF and Soluble Epoxide Hydrolase in LSL-KrasG12D/Pdx-1-Cre Mice

PubMed Central

LIAO, JIE; HWANG, SUNG HEE; LI, HAONAN; LIU, JUN-YAN; HAMMOCK, BRUCE D.; YANG, GUANG-YU

2016-01-01

Mutation of Kirsten rat sarcoma viral oncogene homolog (KRAS) and chronic pancreatitis are the most common pathogenic events involved in human pancreatic carcinogenesis. In the process of long-standing chronic inflammation, aberrant metabolites of arachidonic acid play a crucial role in promoting carcinogenesis, in which the soluble epoxide hydrolase (sEH), as a pro-inflammatory enzyme, generally inactivates anti-inflammatory epoxyeicosatrienoic acids (EETs). Herein, we determined the effect of our newly-synthesized novel compound trans-4-{4-[3-(4-chloro-3-trifluoromethyl-phenyl)-ureido]-cyclohexyloxy}-pyridine-2-carboxylic acid methylamide (t-CUPM), a dual inhibitor of sEH and RAF1 proto-oncogene serine/threonine kinase (c-RAF), on inhibiting the development of pancreatitis and pancreatic intraepithelial neoplasia (mPanIN) in LSL-KrasG12D/Pdx1-Cre mice. The results showed that t-CUPM significantly reduced the severity of chronic pancreatitis, as measured by the extent of acini loss, inflammatory cell infiltration and stromal fibrosis. The progression of low-grade mPanIN I to high-grade mPanIN II/III was significantly suppressed. Inhibition of mutant Kras-transmitted phosphorylation of mitogen-activated protein kinase’s kinase/extracellular signal-regulated kinases was demonstrated in pancreatic tissues by western blots. Quantitative real-time polymerase chain reaction analysis revealed that t-CUPM treatment significantly reduced the levels of inflammatory cytokines including tumor necrosis facor-α, monocyte chemoattractant protein-1, as well as vascular adhesion molecule-1, and the levels of Sonic hedgehog and Gli transcription factor (Hedgehog pathway). Analysis of the eicosanoid profile revealed a significant increase of the EETs/dihydroxyeicosatrienoic acids ratio, which further confirmed sEH inhibition by t-CUPM. These results indicate that simultaneous inhibition of sEH and c-RAF by t-CUPM is important in preventing chronic pancreatitis and carcinogenesis

Vaginal toxic shock reaction triggering desquamative inflammatory vaginitis.

PubMed

Pereira, Nigel; Edlind, Thomas D; Schlievert, Patrick M; Nyirjesy, Paul

2013-01-01

The study aimed to report 2 cases of desquamative inflammatory vaginitis associated with toxic shock syndrome toxin 1 (TSST-1)-producing Staphylococcus aureus strains. Case report of 2 patients, 1 with an acute and 1 with a chronic presentation, diagnosed with desquamative inflammatory vaginitis on the basis of clinical findings and wet mount microscopy. Pretreatment and posttreatment vaginal bacterial and yeast cultures were obtained. Pretreatment vaginal bacterial cultures from both patients grew TSST-1-producing S. aureus. Subsequent vaginal bacterial culture results after oral antibiotic therapy were negative. Desquamative inflammatory vaginitis may be triggered through TSST-1-mediated vaginal toxic shock reaction.

Monocyte-derived dendritic cells from patients with cervical intraepithelial lesions

PubMed Central

Lopes, Angela Maria Moed; Michelin, Márcia Antoniazi; Murta, Eddie Fernando Cândido

2017-01-01

Immunotherapy with dendritic cells (DCs) is a great promise for the treatment of neoplasms. However, the obtainment and protocol of differentiation of these cells may depend on extrinsic factors such as the tumor itself. The aim of the present study was to verify the influence of cervical neoplasia on different protocols of differentiation of monocyte-derived DCs resulting in an increased maturation phenotype. A total of 83 women were included in the study. The patients were grouped in low-grade squamous intraepithelial lesion (LSIL) (n=30), high-grade squamous intraepithelial lesion (HSIL) (n=22), cervical cancer (n=10) and healthy patients (n=21) groups. The mononuclear cells of patients were subjected to three differentiation protocols. In protocol I (pI), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and tumor necrosis factor (TNF)-α were used for the differentiation of mature DCs (pIDCs). In protocol II (pII), monocytes were stimulated with GM-CSF, IL-4, TNF-α and activated lymphocytes in the absence of non-adherent cells (pIIDCs). In protocol III (pIII), monocytes were stimulated with GM-CSF, IL-4, TNF-α and activated lymphocytes in the presence of non-adherent cells (pIIIDCs). These cells were evaluated by flow cytometry for the expression of maturation markers such as cluster of differentiation (CD)11c, CD86 and human leukocyte antigen-antigen D related (HLA-DR). The main cytokines secreted (IL-4, IL-12 and transforming growth factor-β) were measured by ELISA. Our results indicate a significantly lower mature profile of pIIDCs and a significant increase in CD11c+ pIIIDCs able to produce IL-12 (P=0.0007). Furthermore, a significant reduction in cervical cancer HLA-DR+ pIDCs (P=0.0113) was also observed. HSIL patients exhibited a higher percentage of HLA-DR+ pIIDCs (P=0.0113), while LSIL patients had a lower percentage of CD11c+ pIIIDCs (P=0.0411). These findings suggest that the extent of cervical lesions affects the

Monocyte-derived dendritic cells from patients with cervical intraepithelial lesions.

PubMed

Lopes, Angela Maria Moed; Michelin, Márcia Antoniazi; Murta, Eddie Fernando Cândido

2017-03-01

Immunotherapy with dendritic cells (DCs) is a great promise for the treatment of neoplasms. However, the obtainment and protocol of differentiation of these cells may depend on extrinsic factors such as the tumor itself. The aim of the present study was to verify the influence of cervical neoplasia on different protocols of differentiation of monocyte-derived DCs resulting in an increased maturation phenotype. A total of 83 women were included in the study. The patients were grouped in low-grade squamous intraepithelial lesion (LSIL) (n=30), high-grade squamous intraepithelial lesion (HSIL) (n=22), cervical cancer (n=10) and healthy patients (n=21) groups. The mononuclear cells of patients were subjected to three differentiation protocols. In protocol I (pI), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-4 and tumor necrosis factor (TNF)-α were used for the differentiation of mature DCs (pIDCs). In protocol II (pII), monocytes were stimulated with GM-CSF, IL-4, TNF-α and activated lymphocytes in the absence of non-adherent cells (pIIDCs). In protocol III (pIII), monocytes were stimulated with GM-CSF, IL-4, TNF-α and activated lymphocytes in the presence of non-adherent cells (pIIIDCs). These cells were evaluated by flow cytometry for the expression of maturation markers such as cluster of differentiation (CD)11c, CD86 and human leukocyte antigen-antigen D related (HLA-DR). The main cytokines secreted (IL-4, IL-12 and transforming growth factor-β) were measured by ELISA. Our results indicate a significantly lower mature profile of pIIDCs and a significant increase in CD11c + pIIIDCs able to produce IL-12 (P=0.0007). Furthermore, a significant reduction in cervical cancer HLA-DR + pIDCs (P=0.0113) was also observed. HSIL patients exhibited a higher percentage of HLA-DR + pIIDCs (P=0.0113), while LSIL patients had a lower percentage of CD11c + pIIIDCs (P=0.0411). These findings suggest that the extent of cervical lesions affects the

Low-Grade Appendiceal Mucinous Neoplasm Involving the Endometrium and Presenting with Mucinous Vaginal Discharge.

PubMed

Vavinskaya, Vera; Baumgartner, Joel M; Ko, Albert; Saenz, Cheryl C; Valasek, Mark A

2016-01-01

Primary appendiceal mucinous lesions are uncommon and represent a spectrum from nonneoplastic mucous retention cysts to invasive adenocarcinoma. Low-grade appendiceal mucinous neoplasms (LAMNs) represent an intermediate category on this spectrum and can be classified according to whether or not they are confined to the appendix. Although LAMNs are frequently confined to the appendix, they can also spread to the peritoneum and clinically progress as pseudomyxoma peritonei (i.e., mucinous ascites). Thus, the appropriate classification of appendiceal primary neoplasia is essential for prognosis and influences clinical management. In addition, the precise classification, management, and clinical outcome of patients with disseminated peritoneal disease remain controversial. Here, we report an unusual case of LAMN with pseudomyxoma peritonei that initially presented with mucinous and bloody vaginal discharge. Pathological evaluation revealed low-grade appendiceal mucinous neoplasm with secondary involvement of the peritoneum, ovaries, and endometrial surface. Therefore, LAMN should be considered in the differential diagnosis of mucinous vaginal discharge.

Genetic Variants in TAP Are Associated with High-Grade Cervical Neoplasia

PubMed Central

Einstein, Mark H.; Leanza, Suzanne; Chiu, Lydia G.; Schlecht, Nicolas F.; Goldberg, Gary L.; Steinberg, Bettie M.; Burk, Robert D.

2018-01-01

Purpose The transporter associated with antigen processing (TAP) is essential in assembling MHC-I proteins. Human papillomavirus (HPV) evades immune recognition by decreasing class I MHC cell surface expression through down-regulation of TAP1 levels. Consistent with heterogeneity in MHC expression is the individual variability in clearing detectable HPV infections. Genetic polymorphisms in TAP genes may affect protein structure, function, and the ability to clear HPV infection. Experimental Design Case-control study of women with cervical intraepithelial neoplasia (CIN) II or III (n = 114) and women without high-grade CIN (n = 366). Five nonsynonymous single nucleotide polymorphisms (SNP) in TAP1 and TAP2 were genotyped using DNA collected in cervicovaginal lavage samples using microsphere array technology (Luminex ×MAP). HPV typing was done using a PCR-based system with MY09/MY11 primers. TAP1 and TAP2 SNPs were validated by direct sequencing. Results Differences in allele distribution between women with high-grade cervical neoplasia and women without was seen for TAP1 I333V (P = 0.02) and TAP1 D637G (p = 0.01).The odds ratios (OR) for CIN III were significantly lower among carriers of the TAP1 I333V polymorphism (OR, 0.28; 95% confidence interval, 0.1-0.8), and TAP1 D637G polymorphism (OR, 0.27; 95% confidence interval, 0.1-0.7). These associations remained significant even after restricting the evaluation to women who were positive for high-risk HPV types. Conclusions In addition to the down-regulation of MHC-1 by oncogenic HPV, HPV pathogenesis might be facilitated by polymorphisms in the TAP proteins. Identifying TAP polymorphisms may potentially be used to identify women less susceptible to progression to high-grade CIN and cervical cancer. PMID:19188174

Cervical intraepithelial neoplasia (CIN) in African women living with HIV: role and effect of rigorous histopathological review by a panel of pathologists in the HARP study endpoint determination.

PubMed

Doutre, Sylviane; Omar, Tanvier; Goumbri-Lompo, Olga; Kelly, Helen; Clavero, Omar; Zan, Souleymane; Chikandiwa, Admire; Sawadogo, Bernard; Delany-Moretlwe, Sinead; Costes, Valérie; Mayaud, Philippe; Segondy, Michel

2018-01-01

To analyse the effect of the expert end-point committee (EPC) review on histological endpoint classification of cervical intraepithelial neoplasia (CIN). A cohort of women living with HIV were recruited in Burkina Faso (BF) and South Africa (SA) and followed over 18 months. Four-quadrant cervical biopsies were obtained in women with abnormalities detected by at least one screening test. A central review by a panel of five pathologists was organised at baseline and at endline. At baseline the prevalence of high-grade CIN (CIN2+) was 5.1% (28/554) in BF and 23.3% (134/574) in SA by local diagnosis, and 5.8% (32/554) in BF and 22.5% (129/574) in SA by the EPC. At endline the prevalence of CIN2+ was 2.3% (11/483) in BF and 9.4% (47/501) in SA by local diagnosis, and 1.4% (7/483) in BF and 10.2% (51/501) in SA by EPC. The prevalence of borderline CIN1/2 cases was 2.8% (32/1128) and 0.8% (8/984) at baseline and endline. Overall agreement between local diagnosis and final diagnosis for distinguishing CIN2+ from ≤CIN1 was 91.2% (κ=0.82) and 88.9% (κ=0.71) for BF at baseline and endline, and 92.7% (κ=0.79) and 98.7% (κ=0.97) for SA at baseline and endline. Among the CIN1/2 cases, 12 (37.5%) were graded up to CIN2 and 20 (62.5%) were graded down to CIN1 at baseline, and 3 (37.5%) were graded up to CIN2 and 5 (62.5%) were graded down to CIN1 at endline. This study highlights the importance of a centralised rigorous re-reading with exchange of experiences among pathologists from different settings. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Non-specific vaginitis or vaginitis of undetermined aetiology.

PubMed

Faro, S; Phillips, L E

1987-01-01

Vaginitis is a complex syndrome that is probably the most common outpatient disease seen by the gynaecologist. The specific aetiologies of vaginitis are many. One of the most common entities, however, is "non-specific vaginitis" which can be subdivided into: Gardnerella vaginitis, anaerobic vaginosis, and vaginitis of undetermined aetiology. The role of Gardnerella as a causative agent for vaginitis has been studied in depth but its specific role remains controversial. Anaerobic vaginosis can be diagnosed by noting on microscopic examination the presence of clue cells, free-floating bacteria and numerous white blood cells (WBC's). Culturing an aliquot of the vaginal discharge reveals a high number of anaerobes. In addition, this condition responds to antibiotics effective against anaerobes, e.g., metronidazole. Vaginitis of undetermined aetiology is more complex and is characterized by a purulent vaginal discharge, a pH of 4.0-4.6, numerous WBC's, and a high concentration of bacteria. The microbiology of this vaginitis includes many facultative Gram-negative rods and Gram-positive cocci. Anaerobes may be present but do not make up a large component of the endogenous microflora. This condition does not respond to the usual antibiotic therapies employed in treating bacterial vaginitis. Since this condition appears to be primarily an inflammatory reaction, it may be responsive to topical antiinflammatory agents such as benzydamine.

Vaginal cancer

MedlinePlus

Vaginal cancer; Cancer - vagina; Tumor - vaginal ... Most vaginal cancers occur when another cancer, such as cervical or endometrial cancer , spreads. This is called secondary vaginal cancer. Cancer ...

Advanced colorectal adenoma related gene expression signature may predict prognostic for colorectal cancer patients with adenoma-carcinoma sequence.

PubMed

Li, Bing; Shi, Xiao-Yu; Liao, Dai-Xiang; Cao, Bang-Rong; Luo, Cheng-Hua; Cheng, Shu-Jun

2015-01-01

There are still no absolute parameters predicting progression of adenoma into cancer. The present study aimed to characterize functional differences on the multistep carcinogenetic process from the adenoma-carcinoma sequence. All samples were collected and mRNA expression profiling was performed by using Agilent Microarray high-throughput gene-chip technology. Then, the characteristics of mRNA expression profiles of adenoma-carcinoma sequence were described with bioinformatics software, and we analyzed the relationship between gene expression profiles of adenoma-adenocarcinoma sequence and clinical prognosis of colorectal cancer. The mRNA expressions of adenoma-carcinoma sequence were significantly different between high-grade intraepithelial neoplasia group and adenocarcinoma group. The biological process of gene ontology function enrichment analysis on differentially expressed genes between high-grade intraepithelial neoplasia group and adenocarcinoma group showed that genes enriched in the extracellular structure organization, skeletal system development, biological adhesion and itself regulated growth regulation, with the P value after FDR correction of less than 0.05. In addition, IPR-related protein mainly focused on the insulin-like growth factor binding proteins. The variable trends of gene expression profiles for adenoma-carcinoma sequence were mainly concentrated in high-grade intraepithelial neoplasia and adenocarcinoma. The differentially expressed genes are significantly correlated between high-grade intraepithelial neoplasia group and adenocarcinoma group. Bioinformatics analysis is an effective way to study the gene expression profiles in the adenoma-carcinoma sequence, and may provide an effective tool to involve colorectal cancer research strategy into colorectal adenoma or advanced adenoma.

Vaginal Atrophy

MedlinePlus

... an Endocrinologist Search Featured Resource Menopause Map™ View Vaginal Atrophy October 2017 Download PDFs English Editors Christine ... during this time, including vaginal dryness. What is vaginal atrophy? Vaginal atrophy (also referred to as vulvovaginal ...

Vaginal health in contraceptive vaginal ring users - A review.

PubMed

Lete, Iñaki; Cuesta, María C; Marín, Juan M; Guerra, Sandra

2013-08-01

To provide an overview of the available data from clinical studies of vaginal conditions in women who use a vaginal ring as a contraceptive. A systematic review of the literature. Millions of women have already used the ethylene vinyl acetate vaginal ring that releases ethinylestradiol and etonogestrel for contraception. Because of its small size, more than four out of five women using the ring report that they do not feel it, even during sexual intercourse. No colposcopic or cytological changes have been observed in users, although approximately 10% have increased vaginal discharge. While in vitro studies have shown adhesion of Candida yeasts to the vaginal ring surface, clinical studies have not demonstrated a greater incidence of Candida infections compared to users of equivalent oral contraceptives. Some clinical studies suggest a lower incidence of bacterial vaginosis. No interaction exists between concomitant use of the vaginal ring and other drugs or products for vaginal use. The use of a contraceptive vaginal ring does not alter the vaginal ecosystem and therefore does not substantially affect vaginal health.

Penile warty mucoepidermoid carcinoma with features of stratified mucin-producing intra-epithelial lesion and invasive stratified mucin-producing carcinoma.

PubMed

Yorita, Kenji; Kuroda, Naoto; Naroda, Takushi; Tamura, Masato; Ohe, Chisato; Divatia, Mukul; Amin, Mahul B; Cubilla, Antonio L; Kazakov, Dimitry V; Hes, Ondrej; Michal, Michael; Michal, Michal

2018-04-01

Stratified mucin-producing intra-epithelial lesion (SMILE) and invasive stratified mucin-producing carcinoma (ISMC) are recently described cervical and penile lesions. We report an unusual case of mixed variant of penile squamous cell carcinomas with warty, usual and mucoepidermoid SMILE/ISMC features. A 62-year-old Japanese man had a glans penis lesion of one-and-a-half years' duration, suggesting malignancy. Partial penectomy and left inguinal lymphadenectomy were performed. Pathological evaluation revealed a mixed squamous cell carcinoma with warty, mucinous and usual features. The mucinous component resembled mucoepidermoid carcinoma (MEC) and SMILE/ISMC. Glandular differentiation was absent. All the diverse tumour components were negative for p16, which was confirmed by negative human papillomavirus (HPV) genotyping. The mucinous component was diffusely positive for cytokeratin 7 and largely negative for cytokeratin 5 and p63. Fluorescence in-situ hybridisation did not detect rearrangement in the MAML2 or EWSR1 genes. The tumour was pathological stage pT2, pN1 (AJCC prognostic stage group IIIA) and was disease-free 26 months after surgery. The lack of glands in the mucinous areas suggested that MEC should be separated from adenosquamous carcinoma (ASC). Penile SMILE/ISMC may occur without dependence upon HPV status. Further studies will be necessary to determine the pathogenesis and definition of penile SMILE/ISMC, the presence of true MEC arising from the glans penis and the clinicopathological differences of penile ASC, MEC and SMILE/ISMC. Herein, we refer to the SMILE-like penile lesion as 'mucinous penile intra-epithelial neoplasia'. © 2017 John Wiley & Sons Ltd.

Impact of a quadrivalent HPV6/11/16/18 vaccine in Mexican women: public health implications for the region.

PubMed

Lazcano-Ponce, Eduardo; Pérez, Gonzalo; Cruz-Valdez, Aurelio; Zamilpa, Laura; Aranda-Flores, Carlos; Hernández-Nevarez, Pilar; Viramontes, Jose Luis; Salgado-Hernández, Joaquín; James, Margaret; Lu, Shuang; Sattler, Carlos; Haupt, Richard M; Hernández-Avila, Mauricio

2009-08-01

Recognition of human papillomavirus (HPV) as a necessary cause of cervical cancer (CC) led to new perspectives for its control and the demonstration of an effective primary prevention strategy through vaccination. We undertook this study to evaluate the safety, efficacy and immunogenicity of a quadrivalent HPV6/11/16/18 vaccine in Mexican women. A total of 679 Mexican women between 18 and 23 years old participated in two Phase III double-blind, randomized, placebo-controlled clinical trials of a quadrivalent HPV 6/11/16/18 vaccine. Women were enrolled who tested negative for pregnancy and reported having four or less sexual partners during their lifetime. Vaccine or placebo was administered at day 1, month 2 and month 6. Among Mexican women who were naïve to the respective vaccine type at enrollment, the quadrivalent vaccine was highly efficacious, preventing 100% of HPV6/11/16/18-related cervical intraepithelial neoplasia grade 2/3, adenocarcinoma in situ, condyloma and vaginal intraepithelial neoplasia. Statistical significance was not reached for every endpoint due to the limited sample size. Vaccination was generally well tolerated and immunogenic. To widely administer the vaccine, collaborative efforts should be coordinated among public, private and local community sectors. In light of the scarce knowledge of many health professionals with respect to the primary prevention of CC, it will be necessary to educate health providers on the advantages and specific recommendations of HPV vaccines and secondary prevention. Decision making should be based on scientific evidence, allowing health professionals to provide an organized social response that supports the universal right to health.

Cervical cytological abnormalities and human papilloma virus infection in women infected with HIV in Southern India.

PubMed

Thunga, Suchitra; Andrews, Anusmitha; Ramapuram, John; Satyamoorthy, Kapaettu; Kini, Hema; Unnikrishnan, B; Adhikari, Prabha; Singh, Prakhar; Kabekkodu, Shama Prasada; Bhat, Samatha; Kadam, Anagha; Shetty, Avinash K

2016-12-01

The aim of this study was to examine the association between CD4 count, human papilloma virus (HPV) infection, and the risk of cervical intraepithelial neoplasia among HIV-infected women. A cross-sectional study was conducted among 104 HIV-infected women attending an antiretroviral therapy clinic. They underwent Pap smear and cervical HPV DNA testing. The overall prevalence of HPV infection was 57.7%. HPV 16 was the commonest genotype found (38.5%); HPV 16 and 18 put together contributed to 73.3% of HPV infection; 27.5% of HIV-infected women had squamous cell abnormalities. Cervical intraepithelial neoplasia was less likely among women with CD4 count > 500/mm 3 (12%) and in those without opportunistic infections (17.8%). The prevalence of high-risk HPV infection was higher in women with high-grade squamous intraepithelial lesions or greater lesions (85.7%) as compared to women with normal cytology (52.1%). The high prevalence of HPV infection and cervical intraepithelial neoplasia in HIV-infected women warrants the need for regular Pap smear screening in these women and routine HPV vaccination for adolescents to reduce the burden of cervical cancer in India. © 2016 Japan Society of Obstetrics and Gynecology.

Translation and cultural adaptation of the Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD) to evaluate quality of life in women with cervical intraepithelial neoplasia.

PubMed

Fregnani, Cristiane Menezes Sirna; Fregnani, José Humberto Tavares Guerreiro; Paiva, Carlos Eduardo; Barroso, Eliane Marçon; Camargos, Mayara Goulart de; Tsunoda, Audrey Tieko; Longatto-Filho, Adhemar; Paiva, Bianca Sakamoto Ribeiro

2017-01-01

To translate and perform the cultural adaptation of the tool Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD) to the Portuguese language. A descriptive cross-sectional study, with translation and cultural adaptation of the assessment tool performed according to international guidelines and the Functional Assessment of Chronic Illness Therapy (FACIT) protocol group. It involved eight experts, six from Brazil, one from Portugal and one from the United States. After translation and back-translation of the tool, the semantic analysis process was carried out. We randomly included 20 women aged between 18 and 70 years with altered cervical cytology exam, seen at the Department of Prevention and Gynecologic Oncology - Hospital de Câncer de Barretos. The sample consisted of women with low education level. In the first pre-test, ten women participated and half of them considered the questions CD1, CD2 and CD3 as difficult, because they did not understand the meaning of the term "pelvic area". The question CD5, "I worry about spreading the infection", was also considered difficult to understand by five women. After the reconsideration of the expert committee and FACIT group, the second pre-test was performed. At this stage, we concluded that the previously raised understanding problems had been solved. The translated version of FACIT-CD in universal Portuguese language is equivalent to the original version in English and was easily understood by patients with cervical intraepithelial neoplasia. Traduzir e adaptar o instrumento Functional Assessment of Chronic Illness Therapy - Cervical Dysplasia (FACIT-CD), para a língua portuguesa. Estudo descritivo, transversal, com metodologia de tradução e adaptação cultural de instrumento de avaliação, realizado por meio de diretrizes internacionais e seguindo o protocolo do grupo Functional Assessment of Chronic Illness Therapy (FACIT). Envolveu oito especialistas, sendo seis nativos do Brasil

Evaluation of PpIX formation in Cervical Intraepithelial Neoplasia I (CIN) using widefield fluorescence images

NASA Astrophysics Data System (ADS)

Carbinatto, Fernanda M.; Inada, Natalia M.; Fortunato, Thereza C.; Lombardi, Welington; da Silva, Eduardo V.; Vollet Filho, José D.; Kurachi, Cristina; Pratavieira, Sebastião.; Bagnato, Vanderlei S.

2016-03-01

Optical techniques has been described as auxiliary technology for screening of neoplasia because shows the potential for tissues differentiation in real-time and it is a noninvasive detection and safe. However, only endogenous fluorophores presents the lesion may be insufficient and needed of the administration of the fluorophores synthesized, such as, precursor molecule of protoporphyrin IX (PpIX) induced by 5- aminolevulinic acid and your derivatives. Topical application of methylaminolevulinate (MAL), induces formation of the endogenous photosensitizer, PpIX in tissues where carcinogenesis has begun. The PpIX tend to accumulate in premalignant and malignant tissues and the illumination with light with appropriate wavelength beginning to excitation of PpIX fluorescence, which helps to localize PpIX-rich areas and identify potentially malignant tissues. The aim of the study is to evaluate the production of PpIX in the cervix with CIN I through of the fluorescence images captured after 1 hour of cream application. It was possible to visualize PpIX fluorescence in cervix and it was possible to observe the selectivity in fluorescence in squamous-columnar junction, which a pre-cancerous condition (CIN) and usually is localized. Through the image processing it was possible to quantify the increase of red fluorescence. For the CIN I the increase of red fluorescence was approximately of 4 times indicating a good PpIX formation.

Analysis of Vaginal Cell Populations during Experimental Vaginal Candidiasis

PubMed Central

Fidel, Paul L.; Luo, Wei; Steele, Chad; Chabain, Joseph; Baker, Marc; Wormley, Floyd

1999-01-01

Studies with an estrogen-dependent murine model of vaginal candidiasis suggest that local cell-mediated immunity (CMI) is more important than systemic CMI for protection against vaginitis. The present study, however, showed that, compared to uninfected mice, little to no change in the percentage or types of vaginal T cells occurred during a primary vaginal infection or during a secondary vaginal infection where partial protection was observed. Furthermore, depletion of polymorphonuclear leukocytes (PMN) had no effect on infection in the presence or absence of pseudoestrus. These results indicate a lack of demonstrable effects by systemic CMI or PMN against vaginitis and suggest that if local T cells are important, they are functioning without showing significant increases in numbers within the vaginal mucosa during infection. PMID:10338532

Vaginal Toxic Shock Reaction Triggering Desquamative Inflammatory Vaginitis

PubMed Central

Pereira, Nigel; Edlind, Thomas D.; Schlievert, Patrick M.; Nyirjesy, Paul

2012-01-01

Objective To report two cases of desquamative inflammatory vaginitis (DIV) associated with toxic shock syndrome toxin-1 (TSST-1)-producing Staphylococcus aureus strains. Materials and Methods Case report of two patients, one with an acute and one with a chronic presentation, diagnosed with DIV on the basis of clinical findings and wet mount microscopy. Pre- and posttreatment vaginal bacterial and yeast cultures were obtained. Results Pretreatment vaginal bacterial cultures from both patients grew TSST-1-producing S. aureus. Subsequent vaginal bacterial cultures following oral antibiotic therapy were negative. Conclusions DIV may be triggered through TSST-1-mediated vaginal toxic shock reaction. PMID:23222054

Abnormal anal cytology risk in women with known genital squamous intraepithelial lesion.

PubMed

do Socorro Nobre, Maria; Jacyntho, Claudia Marcia; Eleutério, José; Giraldo, Paulo César; Gonçalves, Ana Katherine

2016-01-01

The purpose of this study was to assess the risk of abnormal anal cytology in women with known genital squamous intraepithelial lesion. This study evaluated 200 women with and without genital squamous intraepithelial lesion who were recruited for anal Pap smears. Women who had abnormal results on equally or over atypical squamous cells of undetermined significance were classified as having abnormal anal cytology. A multiple logistic regression analysis (stepwise) was performed to identify the risk for developing abnormal anal cytology. Data were analyzed using the SPSS 20.0 program. The average age was 41.09 (±12.64). Of the total participants, 75.5% did not practice anal sex, 91% did not have HPV-infected partners, 92% did not have any anal pathology, and 68.5% did not have anal bleeding. More than half (57.5%) had genital SIL and a significant number developed abnormal anal cytology: 13% in the total sample and 17.4% in women with genital SIL. A significant association was observed between genital squamous intraepithelial lesion and anal squamous intraepithelial lesion (PR=2.46; p=0.03). In the logistic regression model, women having genital intraepithelial lesion were more likely to have abnormal anal Pap smear (aPR=2.81; p=0.02). This report shows that women with genital squamous intraepithelial lesion must be more closely screened for anal cancer. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

p16INK4A expression as biomarker for HPV 16-related vulvar neoplasias.

PubMed

Riethdorf, Sabine; Neffen, Eduardo F; Cviko, Aida; Löning, Thomas; Crum, Christopher P; Riethdorf, Lutz

2004-12-01

Up-regulation of p16INK4A is associated with high-risk human papillomavirus (HPV) in preinvasive and invasive cervical neoplasia. However, its expression in vulvar carcinomas, which have a diverse pathogenesis, has not been extensively studied. One hundred seventy-seven vulvar intraepithelial neoplasms (VIN), squamous cell carcinomas (SCC), and benign squamous epithelia were analyzed for p16 expression. RNA/RNA in situ hybridization was used to detect HPV 16 E6/E7 transcripts in 112. Ninety-five percent of VIN 3 and basaloid or warty SCCs (76/80) and 4% of keratinizing SCC (2/48) were moderately to strongly immunopositive for p16, which localized to nucleus and cytoplasm; 52/58 analyzed (90%) contained HPV 16 transcripts. The positive predictive value (PPV) of moderate to strong diffuse p16 immunostaining and HPV positivity for the diagnosis of VIN 3 and of basaloid or warty SCC was 97% and 95%, respectively. Conversely, 94% of keratinizing SCC contained heterogeneous staining, and when present, it was strictly cytoplasmic and frequently localized to the cells at the epithelial-stromal interface. Benign squamous epithelia were p16 negative, with the exception of lichen sclerosus, which contained focal and heterogeneously p16 positive in 42%. As in the cervix, intense diffuse p16 expression supports an HPV-related neoplastic process in vulvar neoplasia, irrespective of the level of differentiation. Up-regulation of p16 at the epithelial-stromal interface in HPV negative keratinizing SCCs is consistent with an HPV-independent response to alterations associated with invasion. These disparate patterns of p16 expression underscore 2 different mechanisms for p16 expression in HPV-related and HPV-unrelated vulvar carcinomas.

Vaginal Atrophy

MedlinePlus

... syndrome of menopause (GSM) increases your risk of: Vaginal infections. Changes in the acid balance of your vagina makes vaginal infections (vaginitis) more likely. Urinary problems. Urinary changes associated ...

Sexual dysfunction after colpectomy and vaginal reconstruction with a vertical rectus abdominis myocutaneous flap.

PubMed

Løve, Uffe S; Sjøgren, Pia; Rasmussen, Peter; Laurberg, Søren; Christensen, Henrik K

2013-02-01

The use of the vertical rectus abdominis myocutaneous flap in reconstruction after abdominoperineal resection or pelvic exenteration for neoplasia is well documented. However, functional outcomes after vaginal reconstruction, including sexual function, are poorly described. This study aimed to examine sexual function in women following extensive pelvic surgery with colpectomy and vaginal reconstruction with the use of a vertical rectus abdominis myocutaneous flap. This study is a retrospective review of medical records in combination with patient questionnaires. Nonresponders were followed up with a second contact. This study was performed at a tertiary care university medical center (Colorectal Section, Department of Surgery P, Aarhus University Hospital, Denmark) All women undergoing pelvic surgery and simultaneous vaginal reconstruction with the use of a vertical rectus abdominis myocutaneous flap between 2004 and 2010 at our department were identified from a patient database. Thirty women who were alive at the time of identification were included in the study. Sexual function before and after surgery was evaluated by the use of the Sexual function Vaginal changes Questionnaire. The main outcome end point was whether the patient was sexually active after vaginal reconstruction. Twenty-six participants (87%) answered the questionnaire. Fifty percent of patients reported an active sex life before surgery. In general, patients reported an unchanged desire for both physical and sexual contact after surgery. However, only 2 patients (14%) reported being sexually active after surgery. This was a retrospective study with a heterogeneous cohort involving several types of cancers and surgical procedures. Factors other than vertical rectus abdominis myocutaneous flap reconstruction itself may interfere with the sexual function. Extensive pelvic surgery with colpectomy leads to sexual dysfunction even when the vagina is reconstructed with a vertical rectus abdominis

Serological responses to papillomavirus group-specific antigens in women with neoplasia of the cervix uteri.

PubMed Central

Dillner, L; Moreno-Lopez, J; Dillner, J

1990-01-01

Certain types of human papillomaviruses have been linked to the development of carcinoma of the cervix uteri. We have analyzed 114 serum specimens from women with cervical intraepithelial neoplasia (CIN) or carcinoma of the cervix uteri for the presence of serum antibodies against purified, disrupted bovine papillomavirus (BPV). The titers of immunoglobulin A (IgA) antibodies against BPV were slightly elevated (P less than 0.025) in the sera from CIN or cervical carcinoma patients compared with the titers of 139 serum specimens from sex- and age-matched healthy controls. In contrast, both the IgG and IgM serum antibody titers against BPV were significantly decreased for CIN and cervical carcinoma patients compared with those of healthy controls (P less than 0.001 and P less than 0.005, respectively). These results suggest that the difference between IgA and IgG or IgM antibodies to papillomavirus group-specific antigens may represent interesting serological parameters that could possibly be used in the epidemiologic study of women at risk for CIN. PMID:2157738

Emphysematous vaginitis.

PubMed

Lima-Silva, Joana; Vieira-Baptista, Pedro; Cavaco-Gomes, João; Maia, Tiago; Beires, Jorge

2015-04-01

Emphysematous vaginitis is a rare condition, characterized by the presence of multiple gas-filled cysts in the vaginal and/or exocervical mucosa. Although its etiology is not completely understood, it is self-limited, with a benign clinical course. Vaginal discharge, sometimes bloody, and pruritus are the most common symptoms. Chronic and acute inflammation can be found, and diseases that impair the immune system and pregnancy have been associated with this condition. A 48-year-old postmenopausal woman, with a history of hysterectomy with several comorbidities, presented with a 4-month history of bloody discharge and vulvar pruritus. Examination showed multiple cystic lesions, 1 to 5 mm, occupying the posterior and right lateral vaginal walls. Speculum examination produced crepitus. Vaginal wet mount was normal, except for diminished lactobacilli; results of Trichomonas vaginalis DNA test and vaginal cultures were negative. Lugol's iodine applied to the vagina was taken up by the intact lesions. Biopsy result showed typical features of emphysematous vaginitis. This is an unusual entity, presenting with common gynecological complaints, and both physicians and pathologists should be aware to prevent misdiagnosis and overtreatment.

Conservative approach to preneoplastic cervical lesions in postmenopause.

PubMed

Vetrano, Giuseppe; Aleandri, Vincenzo; Ciolli, Paola; Scardamaglia, Paola; Pacchiarotti, Arianna; Verrico, Monica; Carboni, Simona; Corosu, Roberto

2008-01-01

To evaluate the recurrence rate of high-grade squamous intraepithelial lesions in postmenopausal women previously submitted to laser CO2 conization and the role of persistent oncogenic HPV types. Fifty-five patients with a cytological diagnosis of high-grade squamous intraepithelial lesions were triaged with a standard colposcopy. Hormonal replacement therapy was considered as significative in influencing cervical trophism. Vaginal smears for microbiological examination were obtained. H-R HPV test was performed by PCR. The follow-up checks including cytology, colposcopy and HVP test were performed for a minimum of 5 years. Histological analysis revealed 19 CIN2 (cervical intraepithelial lesions) and 36 CIN3 lesions. The cumulative failure rate at first treatment was 14%. HPV test was positive for HPV 16 type in all patients. Forty-two patients during the follow up checks resulted negative to cytology, colposcopy and HR HPV test. At the one-year follow-up check, 7 patients revealed normal cytological and abnormal colposcopical findings and persistent positive HR HPV test. At the five-year follow-up check, 14 patients with a normal cytological smear had a recurrence of CIN2/3 and positive HR HPV test. In postmenopause, the correct management of H-R squamous intraepithelial lesions is still debated. However, a satisfactory follow-up is the main requirement for the conservative management. HPV typing in the follow-up is important to detect persistent types to identify women at risk of developing cervical abnormalities. The incidence of cervical neoplasia does not decrease with increasing age. Since HPV positivity predicted subsequent infection, testing postmenopausal patients for the virus may be a cost-effective method of disease prevention.

Clinical significance of the qualification of atypical squamous cells of undetermined significance: An analysis on the basis of histologic diagnoses.

PubMed

Vlahos, N P; Dragisic, K G; Wallach, E E; Burroughs, F H; Fluck, S; Rosenthal, D L

2000-04-01

This study was undertaken to evaluate the significance of further qualification of atypical squamous cells of undetermined significance in routine Papanicolaou smears. A retrospective medical records review was conducted on 316 women whose Papanicolaou smears yielded diagnoses of either atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion or atypical squamous cells of undetermined significance suggestive of a reactive process. The overall incidence of a squamous intraepithelial lesion (cervical intraepithelial neoplasia grades I, II, and III) was higher in the group with atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion than in the group with results suggestive of a reactive process (41.1% vs 22.3%; P =.0344). Women with atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion were 9.7 times more likely to have high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia III) develop than were women with atypical squamous cells of undetermined significance suggestive of a reactive process (95% confidence interval, 1.26-74.64). The incidence of high-grade squamous intraepithelial lesion was higher among women 35 years old (17.8% vs 6.3%; P =.0378). Women with a diagnosis of atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion are more likely to have intraepithelial lesions develop than are those with atypical squamous cells of undetermined significance suggestive of a reactive process. Aggressive evaluation of cases of atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion with colposcopy and cervical biopsies may be appropriate. Age should be considered as an independent factor in the plan of management.

Vaginal Cancer Overview

MedlinePlus

... are here Home > Types of Cancer > Vaginal Cancer Vaginal Cancer This is Cancer.Net’s Guide to Vaginal Cancer. Use the menu below to choose the ... social workers, and patient advocates. Cancer.Net Guide Vaginal Cancer Introduction Statistics Medical Illustrations Risk Factors and ...

Comparison of peroxidase-labeled DNA probes with radioactive RNA probes for detection of human papillomaviruses by in situ hybridization in paraffin sections.

PubMed

Park, J S; Kurman, R J; Kessis, T D; Shah, K V

1991-01-01

A study comparing in situ hybridization using nonradioactive DNA probes directly conjugated with horseradish peroxidase (HRP), and 35S-labeled antisense RNA probes for human papillomavirus (HPV) types 6/11, 16, and 18 was performed on formalin-fixed, paraffin-embedded tissue from 34 lesions of the cervix and vulva. These lesions included exophytic condylomas and intraepithelial and invasive neoplasms. HPV 6/11 was detected in two of four condylomata acuminata by both in situ techniques. HPV 16 was detected in 13 of 30 cases of intraepithelial and invasive neoplasms by both methods. Discordance between the two methods occurred in two instances. The radiolabeled probe but not the HRP probe detected HPV 16 in one case of cervical intraepithelial neoplasia (CIN 3), whereas the converse occurred in one case of vulvar intraepithelial neoplasia (VIN 3). HPV 18 was not detected in any of the specimens by either method. This study demonstrates that nonradioactive HRP-labeled probes for the detection of specific HPV types are as sensitive as the more laborious and potentially hazardous radioactive probes.

Comparison of peroxidase-labeled DNA probes with radioactive RNA probes for detection of human papillomaviruses by in situ hybridization in paraffin sections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, J.S.; Kurman, R.J.; Kessis, T.D.

1991-01-01

A study comparing in situ hybridization using nonradioactive DNA probes directly conjugated with horseradish peroxidase (HRP), and {sup 35}S-labeled antisense RNA probes for human papillomavirus (HPV) types 6/11, 16, and 18 was performed on formalin-fixed, paraffin-embedded tissue from 34 lesions of the cervix and vulva. These lesions included exophytic condylomas and intraepithelial and invasive neoplasms. HPV 6/11 was detected in two of four condylomata acuminata by both in situ techniques. HPV 16 was detected in 13 of 30 cases of intraepithelial and invasive neoplasms by both methods. Discordance between the two methods occurred in two instances. The radiolabeled probe butmore » not the HRP probe detected HPV 16 in one case of cervical intraepithelial neoplasia (CIN 3), whereas the converse occurred in one case of vulvar intraepithelial neoplasia (VIN 3). HPV 18 was not detected in any of the specimens by either method. This study demonstrates that nonradioactive HRP-labeled probes for the detection of specific HPV types are as sensitive as the more laborious and potentially hazardous radioactive probes.« less

Vaginal Microbiomes Associated With Aerobic Vaginitis and Bacterial Vaginosis.

PubMed

Kaambo, Evelyn; Africa, Charlene; Chambuso, Ramadhani; Passmore, Jo-Ann Shelley

2018-01-01

A healthy vaginal microbiota is considered to be significant for maintaining vaginal health and preventing infections. However, certain vaginal bacterial commensal species serve an important first line of defense of the body. Any disruption of this microbial barrier might result in a number of urogenital conditions including aerobic vaginitis (AV) and bacterial vaginosis (BV). The health of the vagina is closely associated with inhabitant microbiota. Furthermore, these microbes maintain a low vaginal pH, prevent the acquisition of pathogens, stimulate or moderate the local innate immune system, and further protect against complications during pregnancies. Therefore, this review will focus on vaginal microbial "health" in the lower reproductive tract of women and on the physiological characteristics that determine the well-being of reproductive health. In addition, we explore the distinct versus shared characteristics of BV and AV, which are commonly associated with increased risk for preterm delivery.

Vaginal Microbiomes Associated With Aerobic Vaginitis and Bacterial Vaginosis

PubMed Central

Kaambo, Evelyn; Africa, Charlene; Chambuso, Ramadhani; Passmore, Jo-Ann Shelley

2018-01-01

A healthy vaginal microbiota is considered to be significant for maintaining vaginal health and preventing infections. However, certain vaginal bacterial commensal species serve an important first line of defense of the body. Any disruption of this microbial barrier might result in a number of urogenital conditions including aerobic vaginitis (AV) and bacterial vaginosis (BV). The health of the vagina is closely associated with inhabitant microbiota. Furthermore, these microbes maintain a low vaginal pH, prevent the acquisition of pathogens, stimulate or moderate the local innate immune system, and further protect against complications during pregnancies. Therefore, this review will focus on vaginal microbial “health” in the lower reproductive tract of women and on the physiological characteristics that determine the well-being of reproductive health. In addition, we explore the distinct versus shared characteristics of BV and AV, which are commonly associated with increased risk for preterm delivery. PMID:29632854

Clinical trial experience with prophylactic human papillomavirus 6/11/16/18 vaccine in young black women.

PubMed

Clark, Liana R; Myers, Evan R; Huh, Warner; Joura, Elmar A; Paavonen, Jorma; Perez, Gonzalo; James, Margaret K; Sings, Heather L; Haupt, Richard M; Saah, Alfred J; Garner, Elizabeth I O

2013-03-01

Human papillomavirus (HPV) is the causative agent of cervical cancer. Black women are disproportionally diagnosed and have higher mortality from cervical cancer in the United States. Here we describe the prophylactic efficacy and safety of a quadrivalent HPV-6/11/16/18 vaccine in black women. A total of 700 black women from Latin America, Europe, and North America (aged 16-24 years) received the vaccine or placebo in one of two studies. Analyses focused on the efficacy and safety of the vaccine. Baseline rates of Chlamydia trachomatis infection and history of past pregnancy were more than twice as high in black women compared with the non-black women who were enrolled in these trials. HPV-6/11/16 or 18 DNA was detected in 18% of black women versus 14.6% in non-black women at day 1. For black women, vaccine efficacy against disease caused by HPV-6/11/16/18 was 100% for cervical intraepithelial neoplasia (0 vs. 15 cases; 95% confidence interval, 64.5%-100%) and 100% for vulvar and vaginal intraepithelial neoplasia and condylomata acuminata (0 vs. 17 cases; 95% confidence interval, 69.3%-100%). There were no serious vaccine-related adverse experiences. A similar proportion of pregnancies resulted in live births (75.8% vaccine; 72.7% placebo) and fetal loss (24.2% vaccine; 27.3% placebo). Prophylactic quadrivalent HPV-6/11/16/18 vaccination of young black women demonstrated high efficacy, safety, and tolerability. HPV vaccination has the potential to reduce cervical cancer-related health disparities both in the United States and around the world. Copyright © 2013 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Long-Term Clinical Outcome after Treatment for High-Grade Cervical Lesions: A Retrospective Monoinstitutional Cohort Study

PubMed Central

Del Mistro, Annarosa; Matteucci, Mario; Insacco, Egle Alba; Onnis, GianLibero; Da Re, Filippo; Baboci, Lorena; Minucci, Daria

2015-01-01

Background. The aim of this retrospective observational study of women treated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was to assess the long-term risk of residual/recurrent high-grade CIN. Materials and Methods. We evaluated 760 women treated by loop electrosurgical excision procedure (684) or conization (76) between 2000 and 2009, and followed up to June 30, 2014 (median follow-up 6.7 years, range 4–14). Visits every 6 months for the first year after treatment and yearly for up to the following 10 years included cytology, colposcopy when indicated, and HPV testing (search and typing). Results. CIN2+ or vaginal intraepithelial neoplasia grade 2 or worse (VAIN2+) was detected in 67 cases (8.8%), 39 at first follow-up and 28 after one/more negative visits. The risk of CIN2+ was higher in case of positive margins (odds ratio (OR) 8.04, 95% CI 4.31–15.0), type 3 transformation zone (OR for CIN3 27.7, 95% CI 2.07–36.9), CIN3+ excision (OR 6.02, 95% CI 1.73–20.9), and positive high-risk HPV test at first follow-up (OR for HPV16: 20.6, 95% CI 6.8–62.6; OR for other hrHPV types: 18.3, 95% CI 5.9–57.0). Conclusion. Residual/recurrent high-grade CIN occurred in <9% cases, and the risk was associated with transformation zone type, lesion grade, margins status, and hrHPV test result at 6–12 months of follow-up. PMID:26180819

Human Papilloma Virus and Squamous Cell Carcinoma of the Anus

PubMed Central

Gami, Bhavna; Kubba, Faris; Ziprin, Paul

2014-01-01

The incidence of anal cancer is increasing. In the UK, the incidence is estimated at approximately 1.5 per 100,000. Most of this increase is attributed to certain at-risk populations. Persons who are human immunodeficiency virus (HIV)–positive and men who have sex with men (MSM), Organ transplant recipients, women with a history of cervical cancer, human papilloma virus (HPV), or cervical intraepithelial neoplasia (CIN) are known to have a greater risk for anal cancer. This paper will focus on HPV as a risk factor for anal intraepithelial neoplasia (AIN) and discusses the etiology, anatomy, pathogenesis, management of squamous cell carcinoma (SCC) of the anus. PMID:25288893

Treatment of postmenopausal vaginal atrophy with 10-μg estradiol vaginal tablets.

PubMed

Panay, Nick; Maamari, Ricardo

2012-03-01

Postmenopausal estrogen deficiency can lead to symptoms of urogenital atrophy. Individuals with urogenital atrophy have symptoms that include vaginal dryness, vaginal and vulval irritation, vaginal soreness, pain and burning during urination (dysuria), increased vaginal discharge, vaginal odour, vaginal infections, recurrent urinary tract infections, pain associated with sexual activity (dyspareunia) and vaginal bleeding associated with sexual activity. Despite the frequency and effects of vaginal atrophy symptoms, they are often under-reported and, consequently, under-treated. Therefore, care of a menopausal woman should include a physical assessment of vaginal atrophy and a dialogue between the physician and the patient that explores existing symptoms and their effect on vulvovaginal health, sexuality and quality-of-life issues. The development of the ultra-low-dose 10-µg estradiol vaginal tablets is in line with the requirements of regulatory agencies and women's health societies regarding the use of the lowest effective hormonal dose. Because of its effectiveness and safety profiles, in addition to its minimal systemic absorption, the 10-µg estradiol vaginal tablet can offer greater reassurance to health-care providers and postmenopausal women with an annual estradiol administration of only 1.14 mg.

Premenarchal, recurrent vaginal discharge associated with an incomplete obstructing longitudinal vaginal septum.

PubMed

Hansen, Keith A; DeWitt, Jason

2005-12-01

To describe an unusual, premenarchal presentation of an obstructive vaginal anomaly. Case Report. University Medical Center. Premenarchal subject Vaginogram, vaginal septum resection. Vaginal septum resection with resolution of vaginal discharge. This case demonstrates some of the typical features of uterus didelphys bicollis with incomplete obstructing hemivagina, but had a unique presentation with premenarchal, recurrent vaginal discharge. Typically, patients with an obstructing mullerian anomaly present after menarche with pelvic pain and a mass. The vaginogram assists in the preoperative definition of abnormal anatomy which allows the surgeon to develop the most appropriate surgical approach. Resection of this incompletely obstructing vaginal septum resulted in resolution of the recurrent vaginal discharge.

Hysterectomy - vaginal - discharge

MedlinePlus

Vaginal hysterectomy - discharge; Laparoscopically assisted vaginal hysterectomy - discharge; LAVH - discharge ... you were in the hospital, you had a vaginal hysterectomy. Your surgeon made a cut in your ...

Vaginal foreign bodies.

PubMed

Stricker, T; Navratil, F; Sennhauser, F H

2004-04-01

To evaluate the clinical features and outcome in girls with a vaginal foreign body. Retrospective review of medical records of 35 girls with a vaginal foreign body seen in an outpatient clinic for paediatric and adolescent gynaecology between 1980 and 2000. The ages ranged from 2.6 to 9.2 years. The most common symptom was blood-stained vaginal discharge/vaginal bleeding (49%). Duration of symptoms varied from 1 day to 2 years. Fifty-four percent of the patients recalled insertion of the foreign object, usually by the girl herself. All but three patients (91%) either recalled insertion of the foreign object and/or had vaginal bleeding or blood-stained or foul-smelling vaginal discharge, and/or visualization or palpation of the foreign body in physical examination. Symptoms resolved after removal of the foreign body followed by a single irrigation with Providon-Iod (Betadine). In the majority of patients a carefully obtained history and physical examination suggest the diagnosis of a vaginal foreign object. The leading symptoms are vaginal bleeding and blood-stained or foul smelling vaginal discharge. Removal of the foreign object followed by a single irrigation with Providon-Iod is the definitive treatment and does not require additional measures.

Clinical characteristics of aerobic vaginitis and its association to vaginal candidiasis, trichomonas vaginitis and bacterial vaginosis.

PubMed

Jahic, Mahira; Mulavdic, Mirsada; Nurkic, Jasmina; Jahic, Elmir; Nurkic, Midhat

2013-12-01

Examine clinical characteristics of aerobic vaginitis and mixed infection for the purpose of better diagnostic accuracy and treatment efficiency. Prospective research has been conducted at Clinic for Gynecology and Obstetrics, Department for Microbiology and Pathology at Polyclinic for laboratory diagnostic and Gynecology and Obstetrics Department at Health Center Sapna. Examination included 100 examinees with the signs of vaginitis. anamnesis, clinical, gynecological and microbiological examination of vaginal smear. The average age of the examinees was 32,62±2,6. Examining vaginal smears of the examinees with signs of vaginitis in 96% (N-96) different microorganisms have been isolated, while in 4% (N-4) findings were normal. AV has been found in 51% (N-51) of the examinees, Candida albicans in 17% (N-17), BV in 15% (N-15), Trichomonas vaginalis in 13% (N-13). In 21% (N-21) AV was diagnosed alone while associated with other agents in 30% (N-30). Most common causes of AV are E. coli (N-55) and E. faecalis (N-52). AV and Candida albicanis have been found in (13/30, 43%), Trichomonas vaginalis in (9/30, 30%) and BV (8/30, 26%). Vaginal secretion is in 70,05% (N-36) yellow coloured, red vagina wall is recorded in 31,13% (N-16) and pruritus in 72,54% (N-37). Increased pH value of vagina found in 94,10% (N-48). The average pH value of vaginal environment was 5,15±0,54 and in associated presence of AV and VVC, TV and BV was 5,29±0,56 which is higher value considering presence of AV alone but that is not statistically significant difference (p>0,05). Amino-odor test was positive in 29,94% (N-15) of associated infections. Lactobacilli are absent, while leukocytes are increased in 100% (N-51) of the examinees with AV. AV is vaginal infection similar to other vaginal infections. It is important to be careful while diagnosing because the treatment of AV differentiates from treatment of other vaginitis.

Induction of Cervical Neoplasia in the Mouse by Herpes Simplex Virus Type 2 DNA

NASA Astrophysics Data System (ADS)

Anthony, Donald D.; Budd Wentz, W.; Reagan, James W.; Heggie, Alfred D.

1989-06-01

Induction of cervical neoplasia in the mouse cervix by herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) has been reported. The present study was done to determine if transfection with DNA of HSV-2 can induce carcinogenesis in this animal model. Genomic HSV-2 DNA was isolated from infected HEp-2 cells and separated from host cell DNA by cesium chloride density gradient centrifugation. The DNA was applied to mouse cervix for periods of 80-100 weeks. Experimental controls were treated with uninfected genomic HEp-2 cell DNA or with calf thymus DNA. Vaginal cytological preparations from all animals were examined monthly to detect epithelial abnormalities. Animals were sacrificed and histopathology studies were done when cellular changes indicative of premalignant or malignant lesions were seen on vaginal smears. Cytologic and histologic materials were coded and evaluated without knowledge of whether they were from animals treated with virus or control DNA. Premalignant and malignant cervical lesions similar to those that occur in women were detected in 61% of the histologic specimens obtained from animals exposed to HSV-2 DNA. The yield of invasive cancers was 21% in animals treated with HSV-2 DNA. No cancers were detected in mice treated with either HEp-2 or calf thymus DNA. Dysplasia was detected in only one of these control animals.

Value of bacterial culture of vaginal swabs in diagnosis of vaginal infections.

PubMed

Nenadić, Dane; Pavlović, Miloš D

2015-06-01

Vaginal and cervical swab culture is still very common procedure in our country's everyday practice whereas simple and rapid diagnostic methods have been very rarely used. The aim of this study was to show that the employment of simple and rapid diagnostic tools [vaginal fluid wet mount microscopy (VFWMM), vaginal pH and potassium hydroxide (KOH) test] offers better assessment of vaginal environment than standard microbiologic culture commonly used in Serbia. This prospective study included 505 asymptomatic pregnant women undergoing VFWMM, test with 10% KOH, determination of vaginal pH and standard culture of cervicovaginal swabs. Combining findings from the procedures was used to make diagnoses of bacterial vaginosis (BV) and vaginitis. In addition, the number of polymorphonuclear leukocytes (PMN) was determined in each sample and analyzed along with other findings. Infections with Candida albicans and Trichomonas vaginalis were confirmed or excluded by microscopic examination. In 36 (6%) patients cervicovaginal swab cultures retrieved several aerobes and facultative anaerobes, whereas in 52 (11%) women Candida albicans was isolated. Based on VFWMM findings and clinical criteria 96 (19%) women had BV, 19 (4%) vaginitis, and 72 (14%) candidiasis. Of 115 women with BV and vaginitis, pH 4.5 was found in 5, and of 390 with normal findings 83 (21%) had vaginal pH 4.5. Elevated numbers of PMN were found in 154 (30%) women--in 83 (54%) of them VFWMM was normal. Specificity and sensitivity of KOH test and vaginal pH determination in defining pathological vaginal flora were 95% and 81%, and 79% and 91%, respectively. Cervicovaginal swab culture is expensive but almost non-informative test in clinical practice. The use of simpler and rapid methods as vaginal fluid wet mount microscopy, KOH test and vaginal pH offers better results in diagnosis, and probably in the treatment and prevention of sequels of vaginal infections.

A2. Vulval intraepithelial neoplasia (VIN).

PubMed

Hatch, Kenneth D

2006-11-01

VIN 3 is most likely a cancer precursor and is induced by infection with high-risk types of HPV. VIN 3 lesions may be asymptomatic or present with itching and/or burning or the appearance of a vulval lesion (often raised and hyperpig-mented), which may be unifocal or multifocal. All vulval lesions should be biopsied to confirm the diagnosis. Treatment options include laser vaporization, excision or cautery. Long term follow up is essential. © 2006 International Federation of Gynecology and Obstetrics.

Vaginal yeast infection

MedlinePlus

Yeast infection - vagina; Vaginal candidiasis; Monilial vaginitis ... Most women have a vaginal yeast infection at some time. Candida albicans is a common type of fungus. It is often found in small amounts in the ...

Accuracy of dry vaginal self-sampling for detecting high-risk human papillomavirus infection in cervical cancer screening: a cross-sectional study.

PubMed

Haguenoer, K; Giraudeau, B; Gaudy-Graffin, C; de Pinieux, I; Dubois, F; Trignol-Viguier, N; Viguier, J; Marret, H; Goudeau, A

2014-08-01

Cervical cancer screening coverage remains insufficient in most countries. Testing self-collected samples for high-risk human papillomavirus (HR-HPV) could be an alternative to the Pap smear, but costs, sampling methods and transport issues hamper its wide use. Our objective was to compare diagnostic accuracy of 2 vaginal self-collection methods, a dry swab (vsc-DRY) or swab in liquid medium (vsc-LIQ), for detecting HR-HPV cervical infection assessed by a cervical clinician-collected sample in liquid medium (ccc-LIQ). Women 20 to 65 years attending a Pap smear were recruited between September, 2009 and March, 2011. Each sample (3 per woman) underwent HPV DNA testing. Samples were classified as HR-HPV+ with detection of at least one HR-HPV or probable HR-HPV type. Of 734 women included, 722 had complete HPV data. HR-HPV was detected in 20.9% of ccc-LIQ samples. Estimated sensitivity and specificity to detect HR-HPV in vsc-DRY samples were 88.7% and 92.5%, respectively, and in vsc-LIQ samples, 87.4% and 90.9%. Cytology findings were abnormal for 79 women (10.9%): among 27 samples of low-grade squamous intraepithelial lesions, 25 were HR-HPV+ in vsc-DRY, vsc-LIQ and ccc-LIQ samples. Among 6 samples of high-grade squamous intraepithelial lesions, all were HR-HPV+ in vsc-DRY samples, 1 was HR-HPV- in vsc-LIQ samples and 1 was HR-HPV- in ccc-LIQ samples. Vaginal self-sampling with a dry swab is accurate to detect HR-HPV infection as compared with cervical clinician-collection and accurate as compared with cytology results. This cheap and easy-to-ship sampling method could be widely used in a cervical cancer screening program. Copyright © 2014 Elsevier Inc. All rights reserved.

Detection of occult endocervical glandular dysplasia in cervical conization specimens for squamous lesions.

PubMed

Sopracordevole, F; Clemente, N; Alessandrini, L; Di Giuseppe, J; Cigolot, F; Buttignol, M; Ciavattini, A; Canzonieri, V

2017-03-01

The aim of this work was to evaluate the incidence of occult cervical glandular intraepithelial neoplasia (CGIN) and adenocarcinoma of the cervix (AC) in women treated with CO2-laser conization for cervical intraepithelial neoplasia (CIN) or squamocellular cervical cancer (SCC). The medical records of all women with a histological diagnosis of squamous lesions of the uterine cervix (persistent CIN1, CIN2, CIN3 and SCC) who were subsequently treated with CO2-laser conization at our institution, during the period from January 1991 to December 2014, were analyzed in a retrospective case series. Among the 1004 women fulfilling the study inclusion/exclusion criteria, 77 cases (7.7%) of occult glandular lesions (CGIN and AC) were detected on the final cone specimen (48 cases of occult low-grade cervical glandular intraepithelial neoplasia (LCGIN), 25 cases of occult high-grade cervical glandular intraepithelial neoplasia (HCGIN), and four cases of occult "usual-type" AC). No difference in the mean age between women diagnosed with occult glandular lesions and women without occult glandular lesions on the final specimen emerged (39.1±9.3 vs 38.4±9.4, p=0.5). In women with occult LCGIN on cone specimen, mean follow-up of 48 months was reported (range 7-206 months) and no cases of progression to HCGIN or AC were observed. In conclusion, a relatively high rate of occult glandular lesions was found in women treated for squamous lesions. The natural history of CGIN is still uncertain and, in particular, there are some controversies as to whether LCGIN is a precursor lesion of HCGIN or AC. In this context the role of pathologists become very important since the appropriate diagnosis of these lesions could have potential implications in the clinical management of these patients. Copyright © 2017 Elsevier GmbH. All rights reserved.

Effects of Long-Term Vitamin D Supplementation on Regression and Metabolic Status of Cervical Intraepithelial Neoplasia: a Randomized, Double-Blind, Placebo-Controlled Trial.

PubMed

Vahedpoor, Zahra; Jamilian, Mehri; Bahmani, Fereshteh; Aghadavod, Esmat; Karamali, Maryam; Kashanian, Maryam; Asemi, Zatollah

2017-02-01

We are not aware of any study examining the effects of long term vitamin D administration on regression and metabolic status of patients with cervical intraepithelial neoplasia grade 1 (CIN1). This study was performed to evaluate the effects of long-term vitamin D administration on regression and metabolic status of patients with CIN1. This randomized, double-blind, placebo-controlled trial was performed among 58 women diagnosed with CIN1. CIN1 diagnosis was performed based on specific diagnostic procedures of biopsy, pathological diagnosis, and colposcopy. Patients were randomly allocated into two groups to take 50,000 IU vitamin D3 supplements (n = 29) or placebo (n = 29) every 2 weeks for 6 months. Fasting blood samples were taken at the beginning of the study and end-of-trial to measure related markers. After 6 months of vitamin D administration, greater percentage of women in the vitamin D group had regressed CIN1 (84.6 vs. 53.8%, P = 0.01) than those in the placebo group. Long-term vitamin D supplementation increased serum-25(OH) vitamin D levels in the intervention group compared to the placebo group (+12.3 ± 11.4 vs. -0.1 ± 3.7 ng/mL, P < 0.001). In addition, vitamin D intake led to significant decreases in serum insulin levels (-5.3 ± 7.3 vs. +2.4 ± 5.9 μIU/mL, P < 0.001), homeostasis model of assessment-insulin resistance (-1.2 ± 1.6 vs. +0.5 ± 1.2, P < 0.001), homeostatic model assessment-Beta cell function (P = 0.005) and a significant elevation in quantitative insulin sensitivity check index (+0.03 ± 0.04 vs. -0.007 ± 0.02, P < 0.001) compared with the placebo group. Additionally, significant increases in plasma nitric oxide (NO) (+15.5 ± 10.3 vs. +4.0 ± 13.4 μmol/L, P = 0.001), total antioxidant capacity (TAC) (P = 0.04), total glutathione (GSH) (+11.8 ± 153.5 vs. -294.2 ± 595.1 μmol/L, P = 0.01) and a significant reduction in plasma malondialdehyde (MDA) levels (-0.8 ± 1.0 vs. -0

Animal models of pituitary neoplasia

PubMed Central

Lines, K.E.; Stevenson, M.; Thakker, R.V.

2016-01-01

Pituitary neoplasias can occur as part of a complex inherited disorder, or more commonly as sporadic (non-familial) disease. Studies of the molecular and genetic mechanisms causing such pituitary tumours have identified dysregulation of >35 genes, with many revealed by studies in mice, rats and zebrafish. Strategies used to generate these animal models have included gene knockout, gene knockin and transgenic over-expression, as well as chemical mutagenesis and drug induction. These animal models provide an important resource for investigation of tissue-specific tumourigenic mechanisms, and evaluations of novel therapies, illustrated by studies into multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome in which ∼30% of patients develop pituitary adenomas. This review describes animal models of pituitary neoplasia that have been generated, together with some recent advances in gene editing technologies, and an illustration of the use of the Men1 mouse as a pre clinical model for evaluating novel therapies. PMID:26320859

Clinical Characteristics of Aerobic Vaginitis and Its Association to Vaginal Candidiasis, Trichomonas Vaginitis and Bacterial Vaginosis

PubMed Central

Jahic, Mahira; Mulavdic, Mirsada; Nurkic, Jasmina; Jahic, Elmir; Nurkic, Midhat

2013-01-01

ABSTRACT Aim of the work: Examine clinical characteristics of aerobic vaginitis and mixed infection for the purpose of better diagnostic accuracy and treatment efficiency. Materials and methods: Prospective research has been conducted at Clinic for Gynecology and Obstetrics, Department for Microbiology and Pathology at Polyclinic for laboratory diagnostic and Gynecology and Obstetrics Department at Health Center Sapna. Examination included 100 examinees with the signs of vaginitis. Examination consisted of: anamnesis, clinical, gynecological and microbiological examination of vaginal smear. Results: The average age of the examinees was 32,62±2,6. Examining vaginal smears of the examinees with signs of vaginitis in 96% (N-96) different microorganisms have been isolated, while in 4% (N-4) findings were normal. AV has been found in 51% (N-51) of the examinees, Candida albicans in 17% (N-17), BV in 15% (N-15), Trichomonas vaginalis in 13% (N-13). In 21% (N-21) AV was diagnosed alone while associated with other agents in 30% (N-30). Most common causes of AV are E. coli (N-55) and E. faecalis (N-52). AV and Candida albicanis have been found in (13/30, 43%), Trichomonas vaginalis in (9/30, 30%) and BV (8/30, 26%). Vaginal secretion is in 70,05% (N-36) yellow coloured, red vagina wall is recorded in 31,13% (N-16) and pruritus in 72,54% (N-37). Increased pH value of vagina found in 94,10% (N-48). The average pH value of vaginal environment was 5,15±0,54 and in associated presence of AV and VVC, TV and BV was 5,29±0,56 which is higher value considering presence of AV alone but that is not statistically significant difference (p>0,05). Amino-odor test was positive in 29,94% (N-15) of associated infections. Lactobacilli are absent, while leukocytes are increased in 100% (N-51) of the examinees with AV. Conclusion: AV is vaginal infection similar to other vaginal infections. It is important to be careful while diagnosing because the treatment of AV differentiates from

Pregnancy outcomes after chemotherapy for trophoblastic neoplasia.

PubMed

Garcia, Mila Trementosa; Lin, Lawrence Hsu; Fushida, Koji; Francisco, Rossana Pulcineli Vieira; Zugaib, Marcelo

2016-12-01

The successful development of chemotherapy enabled a fertilitysparing treatment for patients with trophoblastic neoplasia. After disease remission, the outcome of a subsequent pregnancy becomes a great concern for these women. To analyze existing studies in the literature that describe the reproductive outcomes of patients with trophoblastic neoplasia treated with chemotherapy. Systematic review was performed searching for articles on Medline/ Pubmed, Lilacs and Cochrane Library databases, using the terms "gestational trophoblastic disease" and "pregnancy outcome". A total of 18 articles were included. No evidence of decreased fertility after chemotherapy for trophoblastic neoplasia was observed. The abortion rates in patients who conceived within 6 months after chemotherapy was higher compared to those who waited longer. Some studies showed increased rates of stillbirth and repeat hydatidiform moles. Only one work showed increased congenital abnormalities. The pregnancies conceived after chemotherapy for trophoblastic neoplasia should be followed with clinical surveillance due to higher rates of some pregnancy complications. However, studies in the literature provide reassuring data about reproductive outcomes of these patients.

Incidence of macroscopically occult neoplasias in Barrett's esophagus: are random biopsies dispensable in the era of advanced endoscopic imaging?

PubMed

Pohl, Juergen; Pech, Oliver; May, Andrea; Manner, Hendrik; Fissler-Eckhoff, Annette; Ell, Christian

2010-11-01

The gold standard for endoscopic surveillance of Barrett's esophagus (BE) includes targeted biopsies (TBs) from abnormalities as well as stepwise four-quadrant biopsies (4QBs) for detection of invisible high-grade intraepithelial neoplasias (HGINs) or early carcinomas (ECs). In a large mixed BE population, we investigated the rate of HGINs/ECs that are macroscopically occult to enhanced visualization with high-resolution endoscopy plus acetic acid chromoendoscopy. From January 2007 to December 2009, 701 consecutive BE patients were enrolled in a prospective study at a tertiary referral center. Of these, 406 patients had a history of HGIN/EC (high-risk group) and 295 patients did not (low-risk group). In 701 patients, 459 TBs and 5,485 4QBs were obtained. Altogether, 92 patients with 132 lesions containing HGINs/ECs were detected. For the diagnosis of HGINs/ECs, patient-related sensitivity and specificity rates of endoscopic imaging with TBs were 96.7 and 66.5%, with a positive and negative predictive value of 30.4 and 99.3%, respectively. In the high-risk group, 4QBs identified three additional patients (3.3%) with macroscopically occult HGINs/ECs. In the low-risk group, no HGINs/ECs were identified with either biopsy approach. Advanced endoscopic imaging identifies the vast majority of BE patients with early neoplasias, and the additive effect of 4QB is minimal. Therefore, in low- and high-risk patients, limiting endoscopic surveillance to guided biopsies is justified in specialized high-volume centers with permanent quality control. However, we do not advocate abandoning 4QB outside this setting.

NEOPLASIA IN SNAKES AT ZOO ATLANTA DURING 1992-2012.

PubMed

Page-Karjian, Annie; Hahne, Megan; Leach, Kate; Murphy, Hayley; Lock, Brad; Rivera, Samuel

2017-06-01

A retrospective study was conducted to review neoplasia of captive snakes in the Zoo Atlanta collection from 1992 to 2012. Of 255 snakes that underwent necropsy and histopathologic examination at Zoo Atlanta during the study period, 37 were observed with neoplasia at necropsy. In those 37 snakes, 42 neoplastic lesions of 18 primary cell types were diagnosed. Thirty-five of those neoplasms (83.3%) were malignant, and of those, 19 were of mesenchymal origin, whereas 14 were of epithelial origin. The median annual rate of neoplasia at necropsy was 12.5% (interquartile range = 2.8-19.5%) over the 21-yr study period. The mean estimated age at death for snakes with neoplasia was 13.2 yr (range, 1-24 yr). Investigating the incidence and clinical significance of neoplasia in captive snakes is vital for developing effective preventative and treatment regimes.

A patient-reported outcome measure to identify occurrence and distress of post-surgery symptoms of WOMen with vulvAr Neoplasia (WOMAN-PRO) - a cross sectional study.

PubMed

Senn, Beate; Eicher, Manuela; Mueller, Michael D; Hornung, René; Fink, Daniel; Baessler, Kaven; Hampl, Monika; Denhaerynck, Kris; Spirig, Rebecca; Engberg, Sandra

2013-04-01

The aim of the study was to describe the (a) symptom experience of women with vulvar intraepithelial neoplasia and vulvar cancer (vulvar neoplasia) during the first week after hospital discharge, and (b) associations between age, type of disease, stage of disease, the extent of surgical treatment and symptom experience. This cross-sectional study was conducted in eight hospitals in Germany and Switzerland (Clinical Trial ID: NCT01300663). Symptom experience after surgical treatment in women with vulvar neoplasia was measured with our newly developed WOMAN-PRO instrument. Outpatients (n=65) rated 31 items. We used descriptive statistics and regression analysis. The average number of symptoms reported per patient was 20.2 (SD 5.77) with a range of 5 to 31 symptoms. The three most prevalent wound-related symptoms were 'swelling' (n=56), 'drainage' (n=54) and 'pain' (n=52). The three most prevalent difficulties in daily life were 'sitting' (n=63), 'wearing clothes' (n=56) and 'carrying out my daily activities' (n=51). 'Tiredness' (n=62), 'insecurity' (n=54) and 'feeling that my body has changed' (n=50) were the three most prevalent psychosocial symptoms/issues. The most distressing symptoms were 'sitting' (Mean 2.03, SD 0.88), 'open spot (e.g. opening of skin or suture)' (Mean 1.91, SD 0.93), and 'carrying out my daily activities' (Mean 1.86, SD 0.87), which were on average reported as 'quite a bit' distressing. Negative associations were found between psychosocial symptom experience and age. WOMAN-PRO data showed a high symptom prevalence and distress, call for a comprehensive symptom assessment, and may allow identification of relevant areas in symptom management. Copyright © 2013 Elsevier Inc. All rights reserved.

Yeast Infection (Vaginal)

MedlinePlus

Yeast infection (vaginal) Overview A vaginal yeast infection is a fungal infection that causes irritation, discharge and intense itchiness ... symptoms Causes The fungus candida causes a vaginal yeast infection. Your vagina naturally contains a balanced mix of yeast, including ...

High association of Cryptosporidium spp. infection with colon adenocarcinoma in Lebanese patients.

PubMed

Osman, Marwan; Benamrouz, Sadia; Guyot, Karine; Baydoun, Martha; Frealle, Emilie; Chabe, Magali; Gantois, Nausicaa; Delaire, Baptiste; Goffard, Anne; Aoun, Albert; Jurdi, Nawaf; Dabboussi, Fouad; Even, Gael; Slomianny, Christian; Gosset, Pierre; Hamze, Monzer; Creusy, Colette; Viscogliosi, Eric; Certad, Gabriela

2017-01-01

The association between Cryptosporidium and human colon cancer has been reported in different populations. However, this association has not been well studied. In order to add new strong arguments for a probable link between cryptosporidiosis and colon human cancer, the aim of this study was to determine prevalence and to identify species of Cryptosporidium among Lebanese patients. Overall, 218 digestive biopsies were collected in Tripoli, Lebanon, from three groups of patients: (i) patients with recently diagnosed colon intraepithelial neoplasia/adenocarcinoma before any treatment (n = 72); (ii) patients with recently diagnosed stomach intraepithelial neoplasia/adenocarcinoma before any treatment (n = 21); and (iii) patients without digestive intraepithelial neoplasia/adenocarcinoma but with persistent digestive symptoms (n = 125). DNA extraction was performed from paraffin-embedded tissue. The presence of the parasite in tissues was confirmed by PCR, microscopic observation and immunofluorescence analysis. We identified a high rate (21%) of Cryptosporidium presence in biopsies from Lebanese patients with recently diagnosed colonic neoplasia/adenocarcinoma before any treatment. This prevalence was significantly higher compared to 7% of Cryptosporidium prevalence among patients without colon neoplasia but with persistent gastrointestinal symptoms (OR: 4, CI: 1.65-9.6, P = 0.001). When the comparison was done against normal biopsies, the risk of infection increased 11-fold in the group of patients with colon adenocarcinoma (OR: 11.315, CI: 1.44-89.02, P = 0.003). This is the first study performed in Lebanon reporting the prevalence of Cryptosporidium among patients with digestive cancer. These results show that Cryptosporidium is strongly associated with human colon cancer being maybe a potential etiological agent of this disease.

High association of Cryptosporidium spp. infection with colon adenocarcinoma in Lebanese patients

PubMed Central

Osman, Marwan; Benamrouz, Sadia; Guyot, Karine; Baydoun, Martha; Frealle, Emilie; Chabe, Magali; Gantois, Nausicaa; Delaire, Baptiste; Goffard, Anne; Aoun, Albert; Jurdi, Nawaf; Dabboussi, Fouad; Even, Gael; Slomianny, Christian; Gosset, Pierre; Hamze, Monzer; Creusy, Colette; Viscogliosi, Eric

2017-01-01

Background The association between Cryptosporidium and human colon cancer has been reported in different populations. However, this association has not been well studied. In order to add new strong arguments for a probable link between cryptosporidiosis and colon human cancer, the aim of this study was to determine prevalence and to identify species of Cryptosporidium among Lebanese patients. Methodology and principal findings Overall, 218 digestive biopsies were collected in Tripoli, Lebanon, from three groups of patients: (i) patients with recently diagnosed colon intraepithelial neoplasia/adenocarcinoma before any treatment (n = 72); (ii) patients with recently diagnosed stomach intraepithelial neoplasia/adenocarcinoma before any treatment (n = 21); and (iii) patients without digestive intraepithelial neoplasia/adenocarcinoma but with persistent digestive symptoms (n = 125). DNA extraction was performed from paraffin-embedded tissue. The presence of the parasite in tissues was confirmed by PCR, microscopic observation and immunofluorescence analysis. We identified a high rate (21%) of Cryptosporidium presence in biopsies from Lebanese patients with recently diagnosed colonic neoplasia/adenocarcinoma before any treatment. This prevalence was significantly higher compared to 7% of Cryptosporidium prevalence among patients without colon neoplasia but with persistent gastrointestinal symptoms (OR: 4, CI: 1.65–9.6, P = 0.001). When the comparison was done against normal biopsies, the risk of infection increased 11-fold in the group of patients with colon adenocarcinoma (OR: 11.315, CI: 1.44–89.02, P = 0.003). Conclusions This is the first study performed in Lebanon reporting the prevalence of Cryptosporidium among patients with digestive cancer. These results show that Cryptosporidium is strongly associated with human colon cancer being maybe a potential etiological agent of this disease. PMID:29261714

Protection against rat vaginal candidiasis by adoptive transfer of vaginal B lymphocytes.

PubMed

De Bernardis, Flavia; Santoni, Giorgio; Boccanera, Maria; Lucciarini, Roberta; Arancia, Silvia; Sandini, Silvia; Amantini, Consuelo; Cassone, Antonio

2010-06-01

Vulvovaginal candidiasis is a mucosal infection affecting many women, but the immune mechanisms operating against Candida albicans at the mucosal level remain unknown. A rat model was employed to further characterize the contribution of B and T cells to anti-Candida vaginal protection. Particularly, the protective role of vaginal B cells was studied by means of adoptive transfer of vaginal CD3(-) CD5(+) IgM(+) cells from Candida-immunized rats to naïve animals. This passive transfer of B cells resulted into a number of vaginal C. albicans CFU approximately 50% lower than their controls. Sorted CD3(-) CD5(+) IgM(+) vaginal B lymphocytes from Candida-infected rats proliferated in response to stimulation with an immunodominant mannoprotein (MP) antigen of the fungus. Importantly, anti-MP antibodies and antibody-secreting B cells were detected in the supernatant and cell cultures, respectively, of vaginal B lymphocytes from infected rats incubated in vitro with vaginal T cells and stimulated with MP. No such specific antibodies were found when using vaginal B cells from uninfected rats. Furthermore, inflammatory and anti-inflammatory cytokines, such as interleukin-2 (IL-2), IL-6 and IL-10, were found in the supernatant of vaginal B cells from infected rats. These data are evidence of a partial anti-Candida protective role of CD3(-) CD5(+) IgM(+) vaginal B lymphocytes in our experimental model.

Vaginal Microbiota.

PubMed

Mendling, Werner

2016-01-01

The knowledge about the normal and abnormal vaginal microbiome has changed over the last years. Culturing techniques are not suitable any more for determination of a normal or abnormal vaginal microbiota. Non culture-based modern technologies revealed a complex and dynamic system mainly dominated by lactobacilli.The normal and the abnormal vaginal microbiota are complex ecosystems of more than 200 bacterial species influenced by genes, ethnic background and environmental and behavioral factors. Several species of lactobacilli per individuum dominate the healthy vagina. They support a defense system together with antibacterial substances, cytokines, defensins and others against dysbiosis, infections and care for an normal pregnancy without preterm birth.The numbers of Lactobacillus (L.) iners increase in the case of dysbiosis.Bacterial vaginosis (BV) - associated bacteria (BVAB), Atopobium vaginae and Clostridiales and one or two of four Gardnerella vaginalis - strains develop in different mixtures and numbers polymicrobial biofilms on the vaginal epithelium, which are not dissolved by antibiotic therapies according to guidelines and, thus, provoke recurrences.Aerobic vaginitis seems to be an immunological disorder of the vagina with influence on the microbiota, which is here dominated by aerobic bacteria (Streptococcus agalactiae, Escherichia coli). Their role in AV is unknown.Vaginal or oral application of lactobacilli is obviously able to improve therapeutic results of BV and dysbiosis.

Stromal and intraepithelial tumor-infiltrating lymphocytes in colorectal carcinoma

PubMed Central

Jakubowska, Katarzyna; Kisielewski, Wojciech; Kańczuga-Koda, Luiza; Koda, Mariusz; Famulski, Waldemar

2017-01-01

The local mechanisms of antitumor immune defense determine the development and organization of the tumor microenvironment, and the composition and relative proportions of the inflammatory cell population affect the quality and characteristics of the immune response. The aim of the present study was to conduct a quantitative morphological evaluation of two types of tumor-infiltrating lymphocyte (TILs) populations, including those located in the stroma and intraepithelial cancer structures, in the invasive front and the center of the tumor in patients with colorectal cancer (CRC). The study included 160 patients with CRC who had undergone surgery. The tissue material was stained with hematoxylin and eosin, as used in routine histopathological diagnosis, and the two TIL populations were observed and counted with light microscopy. The relative extent of infiltration of stromal and intraepithelial TILs into the front and center of the primary tumors was similar. The extent of infiltration by stromal TILs was negatively correlated with the morphological features of tumor progression including the cancer infiltration of blood vessels (P=0.016), the invasion of lymph vessels (P=0.007), perineural invasion (P=0.036), lymph node involvement (P=0.047) and distant metastases (P=0.032). The infiltration by intraepithelial TILs was positively correlated with a desmoplastic reaction (P=0.002). Disease-free survival time was statistically shorter in patients without intraepithelial TILs in the center of the primary tumor mass (P=0.049; hazard ratio = 1.45). These results confirm that the infiltration of TILs into the invasive front and center of the tumor in patients with CRC serves an important role in the invasion and progression of the disease, and should be considered in routine histopathological examinations. PMID:29151905

Intraepithelial lymphocytes in relation to NIH category IV prostatitis in autopsy prostate.

PubMed

Dikov, Dorian; Bachurska, Svitlana; Staikov, Dimitri; Sarafian, Victoria

2015-07-01

Quantitative analysis of the number, normal and pathologic ratios between lymphocytes and epithelial cells (ECs), and the significance of intraepithelial lymphocytes (IELs) in normal prostatic epithelium, benign prostatic hyperplasia (BPH), and high grade prostatic intraepithelial neoplasia (PIN) in relation to NIH category IV prostatitis (histologic prostatitis: HP) was studied in autopsy prostate. IELs were analysed in 59 autopsy prostates, which was routinely embedded in paraffin and immunohistochemically stained for CD3. An average of 300-500 ECs were counted per case. The number of IELs was calculated as the mean/100 ECs. Category IV prostatitis was evaluated using NIH consensus grading system in terms of anatomical localization and grade. In healthy individuals the mean number of IELs/100 ECs was 0.61 ± 0.34% or ≤1 lymphocyte/100 ECs, which is considered as the normal basal level of prostate IELs. In category IV prostatitis, the mean number of IELs/100 ECs was 8.53 ± 3.25% or 5-11 lymphocytes/100 ECs. The number of IELs in both around and inside inflammation areas correlated to the grade and location of HP (P < 0.0001 and P < 0.0003), the presence of acute glandular inflammation (P < 0.0001), the scattered stromal lymphocytes (P = 0.029), and BPH and PIN associated prostatic inflammation (P < 0.0001). The study presents the first attempt to examine and score the basic quantitative values of prostatic IELs in normal prostate and in relation to category IV prostatitis. The detected normal upper limit of CD3+ IELs is 1 lymphocyte/100 ECs in the normal prostate epithelium. This is considered as an organ specific characteristic of the prostate-associated lymphoid tissue (PALT). Values >5 IELs/100 ECs indicate the presence of category IV prostatitis. The severity of inflammation correlates to the number of IELs. There is an intimate link between the quantity of the IELs, the degree of the severity and the localization of category IV

The role of low-level magnification in visual inspection with acetic acid for the early detection of cervical neoplasia.

PubMed

Sankaranarayanan, Rengaswamy; Shastri, Surendra S; Basu, Parthasarathi; Mahé, Cédric; Mandal, Ranajit; Amin, Geethanjali; Roy, Chinmayi; Muwonge, Richard; Goswami, Smriti; Das, Pradip; Chinoy, Roshini; Frappart, Lucien; Patil, Sharmila; Choudhury, Devjani; Mukherjee, Titha; Dinshaw, Ketayun

2004-01-01

Several studies have investigated the accuracy of naked eye visual inspection with acetic acid (VIA) in the early detection of cervical neoplasia. It is not clear whether low-level (2-4x) magnification (VIAM) can improve the sensitivity and specificity of VIA. The accuracy of both VIA and VIAM, provided by independent health workers, were evaluated in three cross-sectional studies involving 18,675 women aged 25-65 years in Kolkata and Mumbai in India. All screened women were investigated with colposcopy and biopsies were obtained based on colposcopy findings. The final disease status was based on the reference standard of histology (if biopsies had been taken) or colposcopy. Data from the studies were pooled to calculate the test characteristics for the detection of high-grade squamous intraepithelial lesions (HSIL). 14.1% and 14.2% were positive on testing with VIA and VIAM respectively. Two hundred twenty-nine were diagnosed with HSIL and 68 with invasive cancer. The pooled sensitivity, specificity, positive and negative predictive values for VIA in detecting high-grade squamous intraepithelial lesions (HSIL) were 60.3% (95% CI: 53.6-66.7), 86.8% (95% CI: 86.3-87.3), 5.9% (95% CI: 5.0-7.0), and 99.4% (95% CI: 99.2-99.5), respectively. The values were 64.2% (95% CI: 57.6-70.4), 86.8% (95% CI: 86.2-87.3), 6.3% (95% CI: 5.3-7.3) and 99.4% (95% CI: 99.3-99.6), respectively, for VIAM. Low-level magnification did not improve the test performance of naked eye visualization of acetic acid impregnated uterine cervix.

Vaginal Cancer—Patient Version

Cancer.gov

Two-thirds of vaginal cancer cases are caused by human papillomavirus (HPV). Vaccines that protect against infection with HPV may reduce the risk of vaginal cancer. When found early, vaginal cancer can often be cured. Start here to find information on vaginal cancer treatment and research.

More frequent vaginal orgasm is associated with experiencing greater excitement from deep vaginal stimulation.

PubMed

Brody, Stuart; Klapilova, Katerina; Krejčová, Lucie

2013-07-01

Research indicated that: (i) vaginal orgasm (induced by penile-vaginal intercourse [PVI] without concurrent clitoral masturbation) consistency (vaginal orgasm consistency [VOC]; percentage of PVI occasions resulting in vaginal orgasm) is associated with mental attention to vaginal sensations during PVI, preference for a longer penis, and indices of psychological and physiological functioning, and (ii) clitoral, distal vaginal, and deep vaginal/cervical stimulation project via different peripheral nerves to different brain regions. The aim of this study is to examine the association of VOC with: (i) sexual arousability perceived from deep vaginal stimulation (compared with middle and shallow vaginal stimulation and clitoral stimulation), and (ii) whether vaginal stimulation was present during the woman's first masturbation. A sample of 75 Czech women (aged 18-36), provided details of recent VOC, site of genital stimulation during first masturbation, and their recent sexual arousability from the four genital sites. The association of VOC with: (i) sexual arousability perceived from the four genital sites and (ii) involvement of vaginal stimulation in first-ever masturbation. VOC was associated with greater sexual arousability from deep vaginal stimulation but not with sexual arousability from other genital sites. VOC was also associated with women's first masturbation incorporating (or being exclusively) vaginal stimulation. The findings suggest (i) stimulating the vagina during early life masturbation might indicate individual readiness for developing greater vaginal responsiveness, leading to adult greater VOC, and (ii) current sensitivity of deep vaginal and cervical regions is associated with VOC, which might be due to some combination of different neurophysiological projections of the deep regions and their greater responsiveness to penile stimulation. © 2013 International Society for Sexual Medicine.

Intermediate-grade squamous intraepithelial lesion may be a valid diagnostic/interpretive category.

PubMed

Ravinsky, Esther; Baker, Patricia

2009-02-01

We undertook this study to assess the characteristics of smears with features intermediate between high-grade squamous intraepithelial lesion (HSIL) and low-grade squamous intraepithelial lesion (ISIL). We also wanted to determine how these smears correlate with high risk biopsy diagnosis and to compare this with the biopsy correlation of LSIL and HSIL. Seventy-four squamous intraepithelial lesion (SIL) smears were identified as intermediate-grade SIL smears taken at colposcopy in a 1 year period. They were correlated with concurrent colposcopically guided biopsies. Thirty-five percent of cases with intermediate-grade SIL smears had a biopsy diagnosis of moderate dysplasia or higher as compared with 12% for LSIL 74% for HSIL. This confirmed our hypothesis that intermediate-grade SIL smears have a rate of biopsy diagnosis of moderate dysplasia or higher intermediate to that of LSIL and HSIL.

Management of aerobic vaginitis.

PubMed

Tempera, Gianna; Furneri, Pio Maria

2010-01-01

Aerobic vaginitis is a new nonclassifiable pathology that is neither specific vaginitis nor bacterial vaginosis. The diversity of this microbiological peculiarity could also explain several therapeutic failures when patients were treated for infections identified as bacterial vaginosis. The diagnosis 'aerobic vaginitis' is essentially based on microscopic examinations using a phase-contrast microscope (at ×400 magnification). The therapeutic choice for 'aerobic vaginitis' should take into consideration an antibiotic characterized by an intrinsic activity against the majority of bacteria of fecal origin, bactericidal effect and poor/absent interference with the vaginal microbiota. Regarding the therapy for aerobic vaginitis when antimicrobial agents are prescribed, not only the antimicrobial spectrum but also the presumed ecological disturbance on the anaerobic and aerobic vaginal and rectal microbiota should be taken into a consideration. Because of their very low impact on the vaginal microbiota, kanamycin or quinolones are to be considered a good choice for therapy. Copyright © 2010 S. Karger AG, Basel.

Helicobacter pylori infection-induced H3Ser10 phosphorylation in stepwise gastric carcinogenesis and its clinical implications.

PubMed

Yang, Tao-Tao; Cao, Na; Zhang, Hai-Hui; Wei, Jian-Bo; Song, Xiao-Xia; Yi, Dong-Min; Chao, Shuai-Heng; Zhang, Li-Da; Kong, Ling-Fei; Han, Shuang-Yin; Yang, Yu-Xiu; Ding, Song-Ze

2018-04-15

Our previous works have demonstrated that Helicobacter pylori (Hp) infection can alter histone H3 serine 10 phosphorylation status in gastric epithelial cells. However, whether Helicobacter pylori-induced histone H3 serine 10 phosphorylation participates in gastric carcinogenesis is unknown. We investigate the expression of histone H3 serine 10 phosphorylation in various stages of gastric disease and explore its clinical implication. Stomach biopsy samples from 129 patients were collected and stained with histone H3 serine 10 phosphorylation, Ki67, and Helicobacter pylori by immunohistochemistry staining, expressed as labeling index. They were categorized into nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, and intestinal-type gastric cancer groups. Helicobacter pylori infection was determined by either 13 C-urea breath test or immunohistochemistry staining. In Helicobacter pylori-negative patients, labeling index of histone H3 serine 10 phosphorylation was gradually increased in nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia groups, peaked at low-grade intraepithelial neoplasia, and declined in high-grade intraepithelial neoplasia and gastric cancer groups. In Helicobacter pylori-infected patients, labeling index of histone H3 serine 10 phosphorylation followed the similar pattern as above, with increased expression over the corresponding Helicobacter pylori-negative controls except in nonatrophic gastritis patient whose labeling index was decreased when compared with Helicobacter pylori-negative control. Labeling index of Ki67 in Helicobacter pylori-negative groups was higher in gastric cancer than chronic atrophic gastritis and low-grade intraepithelial neoplasia groups, and higher in intestinal metaplasia group compared with chronic atrophic gastritis group. In Helicobacter pylori-positive groups, Ki67 labeling index was increased

Sample entropy analysis of cervical neoplasia gene-expression signatures

PubMed Central

Botting, Shaleen K; Trzeciakowski, Jerome P; Benoit, Michelle F; Salama, Salama A; Diaz-Arrastia, Concepcion R

2009-01-01

Background We introduce Approximate Entropy as a mathematical method of analysis for microarray data. Approximate entropy is applied here as a method to classify the complex gene expression patterns resultant of a clinical sample set. Since Entropy is a measure of disorder in a system, we believe that by choosing genes which display minimum entropy in normal controls and maximum entropy in the cancerous sample set we will be able to distinguish those genes which display the greatest variability in the cancerous set. Here we describe a method of utilizing Approximate Sample Entropy (ApSE) analysis to identify genes of interest with the highest probability of producing an accurate, predictive, classification model from our data set. Results In the development of a diagnostic gene-expression profile for cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma of the cervix, we identified 208 genes which are unchanging in all normal tissue samples, yet exhibit a random pattern indicative of the genetic instability and heterogeneity of malignant cells. This may be measured in terms of the ApSE when compared to normal tissue. We have validated 10 of these genes on 10 Normal and 20 cancer and CIN3 samples. We report that the predictive value of the sample entropy calculation for these 10 genes of interest is promising (75% sensitivity, 80% specificity for prediction of cervical cancer over CIN3). Conclusion The success of the Approximate Sample Entropy approach in discerning alterations in complexity from biological system with such relatively small sample set, and extracting biologically relevant genes of interest hold great promise. PMID:19232110

Anal study in immunocompetent women with human papillomavirus related lower genital tract pathology.

PubMed

Donaire, Concepción; Reillo, Marcos; Martínez-Escoriza, Juan C; López-Fernández, José A

2017-04-01

To estimate the prevalence of anal dysplasia in immunocompetent women with cervical intraepithelial dysplasia. We did a prospective cohort study, in which we enrolled 166 women with gynecological pathology related to human papilloma virus (HPV) infection. All patients underwent an anal cytology and HPV detection. Statistical analysis with a 95% confidence interval was used for prevalence calculations. A Χ2 test and Fisher's exact one were used to determine differences between groups of qualitative variables. Differences between normally distributed and non-normally distributed groups in quantitative variables were accounted for using Student's t-test or Mann-Whitney's U test, respectively. Out of the 166 patients studied, high risk HPV in the anal canal was detected in 107 (64.46%) cases. The most prevalent genotype observed was non 16/18 high risk HPV, present in 54 (50.47%) patients. There was no a significant association with smoking, use of condom, anal intercourse, or anal benign pathology. However, a significant correlation between the presence of high risk HPV in the anal canal and the antecedent of condylomas was observed (p=0.047) (CI95%: 1.00%-12.58%). Women with cervical intraepithelial neoplasia (CIN) grade 1 had a significantly increased presence of high risk HPV in the anal canal (p=0.044). Out of the 166 women, 6 (3.61%) had abnormal anal cytology results, and were referred to high-resolution anoscopy. Anal biopsy was performed in these six cases. In 2 patients the biopsy reported low-grade Anal Intraepithelial Neoplasia: 1.20% (0.15%-4.28%). Women with cervical intraepithelial dysplasia have 1.20% prevalence of anal intraepithelial neoplasia, so that it does not seem necessary to screen this population. Copyright © 2017 Elsevier B.V. All rights reserved.

Vaginal Bleeding

MedlinePlus

... bleeding is any vaginal bleeding unrelated to normal menstruation. This type of bleeding may include spotting of ... two or more hours. Normal vaginal bleeding, or menstruation, occurs every 21 to 35 days when the ...

Vaginal Odor

MedlinePlus

... usually don't cause vaginal odors. Neither do yeast infections. Generally, if you have vaginal odor without ... Avoid douching. All healthy vaginas contain bacteria and yeast. The normal acidity of your vagina keeps bacteria ...

Clindamycin Vaginal

MedlinePlus

... an infection caused by an overgrowth of harmful bacteria in the vagina). Clindamycin is in a class ... works by slowing or stopping the growth of bacteria. Vaginal clindamycin cannot be used to treat vaginal ...

Vaginal Diseases

MedlinePlus

Vaginal problems are some of the most common reasons women go to the doctor. They may have ... common problem is vaginitis, an inflammation of the vagina. Other problems that affect the vagina include sexually ...

Successful vaginal delivery at term after vaginal reconstruction with labium minus flaps in a patient with vaginal atresia: A rare case report.

PubMed

Liu, Yu; Wang, Yi-Feng

2017-07-01

We report a case of successful vaginal delivery after vaginal reconstruction with labium minus flaps in a 23-year-old patient with congenital vaginal atresia. The patient primarily presented with amenorrhea and cyclic abdominal pain; transabdominal ultrasonography revealed an enlarged uterus due to hematometra and absence of the lower segment of the vagina. Eight years ago, she had undergone an unsuccessful attempt at canalization at a local hospital. Upon referral to our hospital, she underwent vaginal reconstruction with labium minus flaps. Four months after this procedure, she became pregnant and, subsequently, successfully and safely vaginally delivered a healthy female baby weighing 3250 g at 38 +1 weeks' gestation. The delivery did not involve perineal laceration by lateral episiotomy. To the best of our knowledge, this is the first reported case of successful vaginal delivery at term after vaginal reconstruction with labium minus flaps in a patient with vaginal atresia. © 2017 Japan Society of Obstetrics and Gynecology.

Photodynamic therapy for premalignant lesions of the vulva and vagina: A long-term follow-up study.

PubMed

Choi, Min Chul; Kim, Mi Sun; Lee, Gee Hoon; Jung, Sang Geun; Park, Hyun; Joo, Won Duk; Lee, Chan; Lee, Je Ho; Hwang, Yoon Young; Kim, Seung Jo

2015-07-14

We aimed to evaluate responses to photodynamic therapy (PDT) and its long-term efficacy in preserving normal anatomy and function in women with premalignant lesions of the lower genital tract. Fifteen patients received PDT for vulvar intraepithelial neoplasia (VIN), vaginal intraepithelial neoplasia (VAIN), or vulvar Paget's disease between January 2003 and December 2013. Patients underwent colposcopy and/or vulvoscopy for assessment of lesions. Surface photoillumination with a 630-nm red laser light was applied to the lesions 48 hours after intravenous injection of 2 mg/kg photosensitizer (PSZ; Photogem®). The light dose to the lesions was 150 J/cm 2 . The median age of the 15 patients (VIN II: 3, VIN III: 4, VAIN II: 2, VAIN III: 3, Paget's disease: 3) was 42.3 years. The complete response (CR) rate was 80% (12/15) at the 3-month follow-up and 71.4% (10/14) at the 1-year follow-up. There were two cases of persistent disease at the 3-month follow-up. One patient with persistent disease underwent partial vulvectomy three times for repetitive recurrence, and the other received secondary PDT with topical 5-aminolevulinic acid (5-ALA) and subsequently showed no evidence of disease (NED). Another patient achieved 90% remission through a combination of additional alternative treatments after showing partial response (PR). In two cases of CR, recurrence was observed at the 1-year follow-up. Regarding adverse events, photosensitivity reactions such as facial edema and urticaria occurred in 13.3% (2/15) and perineal pain occurred in one patient. PDT may be an effective alternative treatment for premalignant lesions of the female lower genital tract to preserve normal anatomy and sexual function without therapeutic impairment. Lasers Surg. Med. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Performance of Anal Cytology Compared With High-Resolution Anoscopy and Histology in Women With Lower Anogenital Tract Neoplasia.

PubMed

Albuquerque, Andreia; Sheaff, Michael; Stirrup, Oliver; Cappello, Carmelina; Bowring, Julie; Cuming, Tamzin; de Masi, Anke; Rosenthal, Adam N; Nathan, Mayura

2018-04-05

Information on the performance of anal cytology in women who are high-risk for human papillomavirus-related lesions and the factors that might influence it are largely lacking. Evaluate the performance of anal cytology in women with lower anogenital tract neoplasia. retrospective study including all new referrals of women with a previous history of anogenital neoplasia, from January 2012 to July 2017, with concomitant anal cytology and high-resolution anoscopy with or without biopsies. 636 anal cytology samples and 323 biopsies were obtained from 278 women. Overall sensitivity and specificity of 'any abnormality' on anal cytology to predict 'any abnormality' in histology was 47% (95% CI 41-54%) and 84% (95% CI 73-91%), respectively. For detecting high-grade squamous intraepithelial lesions (HSIL)/cancer, sensitivity was 71% (95% CI 61-79%) and specificity was 73% (95% CI 66-79%). There was a poor concordance between cytological and histological grades (κ=0.147). Cytology had a higher sensitivity to predict HSIL/cancer in immunosuppressed vs. non-immunosuppressed patients (92% vs. 60%, P=0.002). The sensitivity for HSIL detection was higher when two or more quadrants were affected in comparison with only one (86% vs. 57%, P=0.006). A previous history of vulvar HSIL/cancer (OR 1.71, 1.08-2.73; P=0.023), immunosuppression (OR 1.88, 1.17-3.03; P=0.009) and concomitant genital HSIL/cancer (OR 2.51, 1.47-4.29; P=0.001) were risk factors for abnormal cytology. Patient characteristics can influence the performance of anal cytology in women. The sensitivity for detecting anal HSIL/cancer was higher in those immunosuppressed and with more extensive disease.

Definition of a type of abnormal vaginal flora that is distinct from bacterial vaginosis: aerobic vaginitis.

PubMed

Donders, Gilbert G G; Vereecken, Annie; Bosmans, Eugene; Dekeersmaecker, Alfons; Salembier, Geert; Spitz, Bernard

2002-01-01

To define an entity of abnormal vaginal flora: aerobic vaginitis. Observational study. University Hospital Gasthuisberg, Leuven, Belgium. 631 women attending for routine prenatal care or attending vaginitis clinic. Samples were taken for fresh wet mount microscopy of vaginal fluid, vaginal cultures and measurement of lactate, succinate and cytokine levels in vaginal fluid. Smears deficient in lactobacilli and positive for clue cells were considered to indicate a diagnosis of bacterial vaginosis. Aerobic vaginitis was diagnosed if smears were deficient in lactobacilli, positive for cocci or coarse bacilli, positive for parabasal epithelial cells, and/or positive for vaginal leucocytes (plus their granular aspect). Genital complaints include red inflammation, yellow discharge, vaginal dyspareunia. Group B streptococci, escherichia coli, staphylococcus aureus and trichomonas vaginalis are frequently cultured. Vaginal lactate concentration is severely depressed in women with aerobic vaginitis, as in bacterial vaginosis, but vaginal succinate is not produced. Also in contrast to bacterial vaginosis, aerobic vaginitis produces a host immune response that leads to high production of interleukin-6, interleukin-1-beta and leukaemia inhibitory factor in the vaginal fluid. Aerobic vaginitis is associated with aerobic micro-organisms, mainly group B streptococci and E. coli. Its characteristics are different from those of bacterial vaginosis and elicit an important host response. The most severe form of aerobic vaginitis equals desquamative inflammatory vaginitis. In theory, aerobic vaginitis may be a better candidate than bacterial vaginosis as the cause of pregnancy complications, such as ascending chorioamnionitis, preterm rupture of the membranes and preterm delivery.

Spontaneous neoplasia in four captive greater hedgehog tenrecs (Setifer setosus).

PubMed

Khoii, Mina K; Howerth, Elizabeth W; Burns, Roy B; Carmichael, K Paige; Gyimesi, Zoltan S

2008-09-01

Little information is available about diseases and pathology of species within the family Tenrecidae, including the greater hedgehog tenrec (Setifer setosus), a Madagascan insectivore. This report summarizes necropsy and histopathologic findings of neoplasia in four captive greater hedgehog tenrecs. Although only four animals are included in this report, neoplasia seems to be a common and significant source of morbidity and mortality in greater hedgehog tenrecs. Types of neoplasia identified include a thyroid follicular-solid carcinoma, two urinary bladder transitional cell carcinomas, uterine endometrial polyps, and multicentric B-cell lymphoma. Due to small sample size, no etiology could be determined, but genetics, viral infection, pesticide treatment, nutrition, or other environmental factors might contribute to the development of neoplasia in this species. This is the first report of neoplasia in greater hedgehog tenrecs.

Thirty-five years of noninvasive bladder carcinoma: a plea for the use of papillary intraurothelial neoplasia as new terminology.

PubMed

Van der Kwast, Theodorus H; Zlotta, Alexandre R; Fleshner, Neil; Jewett, Michael; Lopez-Beltran, Antonio; Montironi, Roldolfo

2008-12-01

Since the introduction of the World Health Organization (WHO) 1973 terminology for bladder cancer, noninvasive epithelial bladder tumors have consistently been labeled bladder carcinomas. In the WHO 2004 classification the removal of the "carcinoma" label from a small subset of noninvasive bladder carcinomas with indolent behavior created the entity of papillary urothelial neoplasms of low malignant potential, but the remaining noninvasive carcinomas of the urothelial tract retained this label. In this overview, we analyze clinical, pathologic and molecular-genomic findings to support a more evidence-based nomenclature of papillary neoplastic lesions of the urinary tract. In line with the tendency during the last few decades to label flat precancerous lesions of various organs intraepithelial neoplasms, we may now also refer to dysplasia and carcinoma in situ of the urinary tract as low and high grade intraurothelial neoplasia, respectively. To harmonize nomenclature, we now propose that the terms low and high grade papillary urothelial carcinoma be replaced by low and high grade papillary intraurothelial neoplasiafor all noninvasive urothelial cancers.

Amine content of vaginal fluid from untreated and treated patients with nonspecific vaginitis.

PubMed Central

Chen, K C; Forsyth, P S; Buchanan, T M; Holmes, K K

1979-01-01

We examined the vaginal washings from patients with nonspecific vaginitis (NSV) to seek biochemical markers and possible explanations for the signs and symptoms of this syndrome. Seven amines were identified including methylamine, isobutylamine, putrescine, cadaverine, histamine, tyramine, and phenethylamine. These amines may contribute to the symptoms of NSV and may contribute to the elevated pH of the vaginal discharge. They may also be partly responsible for the "fishy" odor that is characteristic of vaginal discharges from these patients. Among the seven amines, putrescine and cadaverine were the most abundant and were present in all vaginal discharges from each of ten patients before treatment. These amines are produced in vitro during growth of mixed vaginal bacteria in chemically defined medium, presumably by decarboxylation of the corresponding amino acids. We hypothesize the anaerobic vaginal organisms, previously shown to be quantitatively increased in NSV, are responsible for the amine production, because metronidazole inhibited the production of amines by vaginal bacteria in vitro, and Haemophilus vaginalis did not produce amines. H. vaginalis did release high concentrations of pyruvic acid and of amino acids during growth in peptone-starch-dextrose medium, whereas, other vaginal flora consumed both pyruvic acid and amino acids in the same medium during growth. These findings suggest that a symbiotic relationship may exist between H. vaginalis and other vaginal flora in patients with NSV. Images PMID:447831

Biopsy and selective recall compared with immediate large loop excision in management of women with low grade abnormal cervical cytology referred for colposcopy: multicentre randomised controlled trial.

PubMed

2009-07-28

To compare the effectiveness of punch biopsy and selective recall for treatment versus a policy of immediate treatment by large loop excision in the management of women with low grade abnormal cervical cytology referred for colposcopy. Multicentre individually randomised controlled trial, nested within the NHS cervical screening programmes. Grampian, Tayside, and Nottingham. 1983 women, aged 20-59, with cytology showing borderline nuclear abnormalities or mild dyskaryosis, October 1999-October 2002. Immediate large loop excision or up to four targeted punch biopsies taken immediately with recall for treatment (by large loop excision) if these showed cervical intraepithelial neoplasia grade II or III or worse. Participants were followed for three years, concluding with an exit colposcopy. Clinical end points: cumulative incidence of cervical intraepithelial neoplasia grade II or worse and grade III or worse at three years. Clinically significant anxiety and depression and self reported after effects assessed six weeks after colposcopy, biopsies, or large loop excision. 879 women (44%) had a normal transformation zone at colposcopy and had no further procedures at that time. Colposcopists were less likely to classify the transformation zone as abnormal when the allocation was large loop excision (603 (60%) in the biopsy and selective recall group; 501 (51%) in the immediate large loop excision group). Of women randomised to biopsy and recall, 157 (16%) required a second clinic visit for treatment. Specimens from almost 60% (n=296) of women who underwent immediate large loop excision showed no cervical intraepithelial neoplasia (31%; n=156) or showed cervical intraepithelial neoplasia grade I (28%; n=140). The percentages of women diagnosed with grade II or worse up to and including the exit examination were 22% (n=216) in the biopsy and recall arm and 23% (n=228) in the immediate large loop excision arm. There was no significant difference between the arms in

Vaginal orgasm is associated with vaginal (not clitoral) sex education, focusing mental attention on vaginal sensations, intercourse duration, and a preference for a longer penis.

PubMed

Brody, Stuart; Weiss, Petr

2010-08-01

Evidence was recently provided for vaginal orgasm, orgasm triggered purely by penile-vaginal intercourse (PVI), being associated with better psychological functioning. Common sex education and sexual medicine approaches might undermine vaginal orgasm benefits. To examine the extent to which women's vaginal orgasm consistency is associated with (i) being told in childhood or adolescence that the vagina was the important zone for inducing female orgasm; (ii) how well they focus mentally on vaginal sensations during PVI; (iii) greater PVI duration; and (iv) preference for above-average penis length.   In a representative sample of the Czech population, 1,000 women reported their vaginal orgasm consistency (from never to almost every time; only 21.9% never had a vaginal orgasm), estimates of their typical foreplay and PVI durations, what they were told in childhood and adolescence was the important zone for inducing female orgasm, their degree of focus on vaginal sensations during PVI, and whether they were more likely to orgasm with a longer than average penis. The association of vaginal orgasm consistency with the predictors noted above. Vaginal orgasm consistency was associated with all hypothesized correlates. Multivariate analysis indicated the most important predictors were being educated that the vagina is important for female orgasm, being mentally focused on vaginal sensations during PVI, and in some analyses duration of PVI (but not foreplay) and preferring a longer than average penis. Focusing attention on penile-vaginal sensation supports vaginal orgasm and the myriad benefits thereof. Brody S, and Weiss P. Vaginal orgasm is associated with vaginal (not clitoral) sex education, focusing mental attention on vaginal sensations, intercourse duration, and a preference for a longer penis. © 2009 International Society for Sexual Medicine.

Vaginal cysts

MedlinePlus

... essential to determine what type of cyst or mass you may have. A mass or bulge of the vaginal wall may be ... to rule out vaginal cancer, especially if the mass appears to be solid. If the cyst is ...

Menopause and the vaginal microbiome.

PubMed

Muhleisen, Alicia L; Herbst-Kralovetz, Melissa M

2016-09-01

For over a century it has been well documented that bacteria in the vagina maintain vaginal homeostasis, and that an imbalance or dysbiosis may be associated with poor reproductive and gynecologic health outcomes. Vaginal microbiota are of particular significance to postmenopausal women and may have a profound effect on vulvovaginal atrophy, vaginal dryness, sexual health and overall quality of life. As molecular-based techniques have evolved, our understanding of the diversity and complexity of this bacterial community has expanded. The objective of this review is to compare the changes that have been identified in the vaginal microbiota of menopausal women, outline alterations in the microbiome associated with specific menopausal symptoms, and define how hormone replacement therapy impacts the vaginal microbiome and menopausal symptoms; it concludes by considering the potential of probiotics to reinstate vaginal homeostasis following menopause. This review details the studies that support the role of Lactobacillus species in maintaining vaginal homeostasis and how the vaginal microbiome structure in postmenopausal women changes with decreasing levels of circulating estrogen. In addition, the associated transformations in the microanatomical features of the vaginal epithelium that can lead to vaginal symptoms associated with menopause are described. Furthermore, hormone replacement therapy directly influences the dominance of Lactobacillus in the microbiota and can resolve vaginal symptoms. Oral and vaginal probiotics hold great promise and initial studies complement the findings of previous research efforts concerning menopause and the vaginal microbiome; however, additional trials are required to determine the efficacy of bacterial therapeutics to modulate or restore vaginal homeostasis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Prevalence of vaginal candidiasis among pregnant women with abnormal vaginal discharge in Maiduguri.

PubMed

Ibrahim, S M; Bukar, M; Mohammed, Y; Mohammed, B; Yahaya, M; Audu, B M; Ibrahim, H M; Ibrahim, H A

2013-01-01

Pregnancy represents a risk factor in the occurrence of vaginal candidiasis. To determine the prevalence and clinical features associated with abnormal vaginal discharge and C. albicans infection in pregnant women. High vaginal swab samples and data on epidemiological characteristics were collected from 400 pregnant women with complaints of abnormal vaginal discharge at booking clinic of University of Maiduguri Teaching Hospital. The data was analysed using SPSS 16.0 statistical software. The prevalence of abnormal vaginal discharge in pregnancy was 31.5%. The frequency of abnormal vaginal discharge was 183 (45.8%) among those aged 20-24 years, 291 (72.8%) in multipara, 223 (55.8%) in those with Primary education and 293 (73.2%) in unemployed. Vulval pruritus 300 (75.0%) was significantly related to abnormal vaginal discharge (P < 0.001). The prevalence of C. albicans was 41%. The frequencies of Vulval itching, Dyspareunia and vulval excoriation among those with candidiasis were 151 (50.3%), 14 (56.0%) and 75 (75.0%) respectively (P < 0.001). The prevalence of abnormal vaginal discharge in pregnancy was high in this study and C. albicans was the commonest cause. It is recommended that a pregnant woman complaining of abnormal vaginal discharge be assessed and Laboratory diagnosis done in order to give appropriate treatment.

Ultrathin endoscopy versus high-resolution endoscopy for diagnosing superficial gastric neoplasia.

PubMed

Toyoizumi, Hirobumi; Kaise, Mitsuru; Arakawa, Hiroshi; Yonezawa, Jin; Yoshida, Yukinaga; Kato, Masayuki; Yoshimura, Noboru; Goda, Ken-ichi; Tajiri, Hisao

2009-08-01

Ultrathin endoscopy (UTE) is an acceptable and cost-effective alternative to EGD with the patient under sedation, although the diagnostic accuracy of UTE is not well established. To compare the diagnostic accuracy of UTE and high-resolution endoscopy (HRE) for superficial gastric neoplasia. Prospective comparative study. Academic center. Patients with or without superficial gastric neoplasia underwent peroral UTE and HRE, back-to-back in a random order while under standard sedation. The procedures were performed by 2 endoscopists who were blinded to the clinical information. The rate of missed lesions and misdiagnosis, sensitivity, and specificity for the diagnosis of gastric neoplasia when using pathology as the reference standard. In total, 126 lesions (41 superficial gastric neoplasias, 85 nonneoplastic lesions) were recorded in 57 enrolled patients. For the diagnosis of gastric neoplasia, the sensitivity of UTE (58.5%) was significantly (P = .021) lower than that of HRE (78%), and the specificity of UTE (91.8%) was significantly (P = .014) lower than that of HRE (100%). The rate of missed lesions and misdiagnosis of gastric neoplasias when using UTE (41.5%) was significantly (P > .001) higher than that of HRE (22.0%). The corresponding rate of neoplasias at the proximal portion (fornix and corpus) when using UTE (29%) was significantly (P = .002) higher than that of HRE (7.2%), although the rates of neoplasias at the distal portion (angulus and antrum) were comparable for UTE and HRE. Small sample numbers in an enriched population. The diagnostic accuracy of UTE is significantly lower than that of HRE for superficial gastric neoplasia, and this difference is particularly striking for neoplasias in the proximal stomach. For UTE to be used as an alternative modality, improvements in optical quality and the incorporation of additional procedures, including close-range observations and chromoendoscopy, are required to enhance visualization.

Clinical response to glycyrrhizinic acid in genital infection due to human papillomavirus and low-grade squamous intraepithelial lesion

PubMed Central

Valencia, Marcelino Hernández; Pacheco, Adia Carrillo; Quijano, Tomás Hernández; Girón, Antonio Vargas; López, Carlos Vargas

2011-01-01

Human papilloma virus (HPV) can infect any of the mucosal areas of the body and cause cervical cancer. Until recently, no specific treatments were available for this condition; therefore, any damaged tissue had to be removed or destroyed, which may have presented obstetrical repercussions for some women. Recently, new drugs have been developed that have shown to be effective for the cure of HPV infection. Glycyrrhizinic acid (GA) has shown fewer side effects and its systemic use makes it possible to reach difficult-to-treat lesions. The purpose of this study was to evaluate the clinical outcome of GA to eliminate the epithelial lesion and HPV. We carried out a longitudinal, descriptive study that included women of reproductive age who were diagnosed with HPV associated with low-grade squamous intraepithelial lesion (LSIL). Subjects began treatment based on GA using two routes of administration - systemic (oral) and topical (spray) - with assessments every month to determine the clinical changes of the lesions through colposcopy and Papanicolaou (Pap) smear. Simple statistics were used along with two-tailed Student's t-test; P<0.05 was considered statistically significant before and after treatment. There were 70 eligible patients, of whom 62 fulfilled the inclusion criteria. Age of subjects was 27.8±9.5 years. At the time of the study, 100% of the patients had HPV infection, 40% were associated with LSIL, and only 16% used a barrier contraceptive (condom) method. Resolution was achieved in all patients from 4 weeks of treatment initiation and improvement was achieved in the majority of patients at 12 weeks (74%) (P<0.001). However, there was persistence of LSIL in 27.7% of patients and only one patient progressed to cervical intraepithelial neoplasia (CIN) II. The use of GA proved to be effective in resolving clinical HPV lesions. For cervical lesions with epithelial changes (LSIL), treatment may be required for a longer period as with other drugs used for this

Modeling human endothelial cell transformation in vascular neoplasias

PubMed Central

Wen, Victoria W.; MacKenzie, Karen L.

2013-01-01

Endothelial cell (EC)-derived neoplasias range from benign hemangioma to aggressive metastatic angiosarcoma, which responds poorly to current treatments and has a very high mortality rate. The development of treatments that are more effective for these disorders will be expedited by insight into the processes that promote abnormal proliferation and malignant transformation of human ECs. The study of primary endothelial malignancy has been limited by the rarity of the disease; however, there is potential for carefully characterized EC lines and animal models to play a central role in the discovery, development and testing of molecular targeted therapies for vascular neoplasias. This review describes molecular alterations that have been identified in EC-derived neoplasias, as well as the processes that underpin the immortalization and tumorigenic conversion of ECs. Human EC lines, established through the introduction of defined genetic elements or by culture of primary tumor tissue, are catalogued and discussed in relation to their relevance as models of vascular neoplasia. PMID:24046386

Vaginal Fistula

MedlinePlus

Vaginal fistula Overview A vaginal fistula is an abnormal opening that connects your vagina to another organ, such as your bladder, colon or rectum. Your ... describe the condition as a hole in your vagina that allows stool or urine to pass through ...

Comparison between vaginal royal jelly and vaginal estrogen effects on quality of life and vaginal atrophy in postmenopausal women: a clinical trial study.

PubMed

Seyyedi, Fatemeh; Kopaei, Mahmoud Rafiean; Miraj, Sepideh

2016-11-01

This study was conducted to evaluate the therapeutic effects of vaginal royal jelly and vaginal estrogen on quality of life and vaginal atrophy in postmenopausal women. This double-blind randomized controlled clinical trial was carried out at gynecology and obstetrics clinics of Hajar Hospital of Shahrekord University of Medical Sciences (Iran) from January 2013 to January 2014. The study was conducted on married postmenopausal women between 50 and 65 years old. Of 120 patients, 30 individuals were excluded based on the exclusion criteria, and 90 women were randomly distributed into three groups of 30 royal jelly vaginal cream 15%, vaginal Premarin, and placebo (lubricant), for three months. At the beginning and the end of the study, quality of life and vaginal cytology assay were evaluated. Data were analyzed by SPSS Version 11. Vaginal cream of royal jelly is significantly more effective than vaginal cream of Premarin and lubricant in improvement of quality of life in postmenopausal women (p<0.05). Moreover, Pap smear results showed that vaginal atrophy in vaginal Premarin group was lower than the other groups (p<0.001), and there was no significant difference between lubricant and royal jelly groups (p=0.89). Administration of vaginal royal jelly was effective in quality-of-life improvement of postmenopausal women. Given to the various properties of royal jelly and its effectiveness on quality of life and vaginal atrophy in postmenopausal women, further studies are recommended for using =royal jelly in improving menopausal symptoms. The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT code: 2014112220043n1. Shahrekord University of Medical Sciences supported this research (project no. 1440).

Stratified mucin-producing intraepithelial lesion with invasive carcinoma: 12 cases with immunohistochemical and ultrastructural findings.

PubMed

Onishi, Junji; Sato, Yuichiro; Sawaguchi, Akira; Yamashita, Atsushi; Maekawa, Kazunari; Sameshima, Hiroshi; Asada, Yujiro

2016-09-01

Stratified mucin-producing intraepithelial lesion (SMILE) is considered to be a variant of adenocarcinoma in situ (defined as intraepithelial malignant glandular epithelium without invasion) or adenosquamous carcinoma in situ of the uterine cervix. However, recent study suggested that SMILE is more similar to high-grade squamous epithelial lesion by their immunohistochemical findings. An invasive form of SMILE "invasive stratified mucin-producing carcinoma (ISMC)" has been also proposed, but immunohistochemical features are not well documented. Therefore, this study aimed to clarify the immunohistochemical characteristics of SMILE and ISMC. Twelve cases of SMILE were found among 445 patients (2.7%) with high-grade intraepithelial lesions or invasive carcinomas, 3 of whom had solely intraepithelial disease with SMILE component (mean age, 37 years; range, 30-48 years) and 9 with invasive carcinomas (mean age, 47 years; range, 37-66 years; including ISMC). Immunohistochemically, SMILE and ISMC were diffusely positive for p16 and CAM5.2, focally for IMP3, and almost negative or only focally positive for p63. Nuclear signals in SMILE and invasive carcinomas were detected by human papillomavirus (HPV) in situ hybridization; 5 cases showed HPV16 and/or HPV18 polymerase chain reaction products. The ultrastructural study of 1 case showed surface microvilli and small vacuolar structure in SMILE; ISMC had mucous-like vacuoles, many mitochondria and intracytoplasmic lumen but lacked tonofilament. These findings were more similar to adenocarcinoma in situ or adenocarcinoma than squamous intraepithelial lesion or squamous cell carcinoma. We suggest that SMILE is an intraepithelial neoplasm and ISMC is an invasive form of SMILE. Copyright © 2016 Elsevier Inc. All rights reserved.

Diabetes Mellitus and Colorectal Neoplasia.

PubMed

Acevedo, Alejandro; Diaz, Yaritza; Perez, Cynthia M; Garau, Maria; Baron, John; Cruz-Correa, Marcia

2012-11-01

Many studies have provided evidence for an association between obesity, physical inactivity, and western diet as risk factors for colorectal cancer (CRC). Few studies directly address the association between type 2 Diabetes Mellitus (DM) and the risk of colorectal lesions at specific anatomic locations. 2,663 subjects with a previous history of adenoma(s) and removal of all current adenomas at study entry were followed for a mean time of three years across three different chemoprevention clinical trials. The primary endpoint was colorectal adenoma recurrence and number of lesions during the treatment phase; the secondary endpoints were presence of advanced colorectal neoplasia (CRN) and location of CRN. Using log linear regression, the effect of DM status on the relative risk (RR) of CRN recurrence, advanced CRN, and location of CRN was assessed. DM status was not significantly associated with incidence of colorectal adenomas, incidence of advanced colorectal lesions, or left-sided colorectal neoplastic lesions. Subjects with DM had a marginally increased risk of right-sided (p= 0.06) colorectal adenomas and a significant increased risk of multiple right-sided adenomas (p=0.03) in the unadjusted model; this association was not significant after adjusting for age and other potential confounders (RR=1.22, 95% CI: 0.85-1.76). We did not observe a statistically significant increased risk in CRN recurrence for overall neoplasia, advanced neoplasia or location of neoplasia in individuals with DM compared to non-DM individuals. However, given the patterns observed in this investigation, future studies with longer follow-up time and longer DM exposure, incorporating objective measurements of type 2 DM might help elucidate the risk of CRN among individuals with DM.

Vaginal lactobacilli profile in pregnant women with normal & abnormal vaginal flora.

PubMed

Yeruva, Thirupathaiah; Rajkumar, Hemalatha; Donugama, Vasundhara

2017-10-01

Lactobacilli species that are better adapted to vaginal environment of women may colonize better and offer protection against vaginal pathogenic bacteria. In this study, the distribution of common Lactobacillus species was investigated in pregnant women. Sixty seven pregnant women were included in the study and vaginal samples were collected for Gram staining. Women were classified as normal vaginal flora, intermediate flora and bacterial vaginosis (BV) based on Nugent's score. Vaginal samples were also collected for the identification of Lactobacillus spp. by multiplex polymerase chain reaction (PCR) profiling of 16S rDNA amplification method. Lactobacillus crispatus (100%) was the most predominant Lactobacillus spp. present in pregnant women with normal flora, followed by L. iners (77%), L. jensenii (74%) and L. helveticus (60%). While, L. iners was commonly present across groups in women with normal, intermediate or BV flora, L. crispatus, L. jensenii and L. helveticus decreased significantly as the vaginal flora changed to intermediate and BV. In women with BV, except L. iners other species of lactobacilli was less frequently prevalent. Species such as L. rhamnosus, L. fermentum, L. paracasei and L. casei were not detected in any vaginal sample. L. crispatus, L. jensinii and L. helveticus were predominant species in women with normal flora. L. crispatus alone or in combination with L. jensinii and L. helveticus may be evaluated for probiotic properties for the prevention and treatment of BV.

Vaginal biogenic amines: biomarkers of bacterial vaginosis or precursors to vaginal dysbiosis?

PubMed Central

Nelson, Tiffanie M.; Borgogna, Joanna-Lynn C.; Brotman, Rebecca M.; Ravel, Jacques; Walk, Seth T.; Yeoman, Carl J.

2015-01-01

Bacterial vaginosis (BV) is the most common vaginal disorder among reproductive age women. One clinical indicator of BV is a “fishy” odor. This odor has been associated with increases in several biogenic amines (BAs) that may serve as important biomarkers. Within the vagina, BA production has been linked to various vaginal taxa, yet their genetic capability to synthesize BAs is unknown. Using a bioinformatics approach, we show that relatively few vaginal taxa are predicted to be capable of producing BAs. Many of these taxa (Dialister, Prevotella, Parvimonas, Megasphaera, Peptostreptococcus, and Veillonella spp.) are more abundant in the vaginal microbial community state type (CST) IV, which is depleted in lactobacilli. Several of the major Lactobacillus species (L. crispatus, L. jensenii, and L. gasseri) were identified as possessing gene sequences for proteins predicted to be capable of putrescine production. Finally, we show in a small cross sectional study of 37 women that the BAs putrescine, cadaverine and tyramine are significantly higher in CST IV over CSTs I and III. These data support the hypothesis that BA production is conducted by few vaginal taxa and may be important to the outgrowth of BV-associated (vaginal dysbiosis) vaginal bacteria. PMID:26483694

Vaginal biogenic amines: biomarkers of bacterial vaginosis or precursors to vaginal dysbiosis?

PubMed

Nelson, Tiffanie M; Borgogna, Joanna-Lynn C; Brotman, Rebecca M; Ravel, Jacques; Walk, Seth T; Yeoman, Carl J

2015-01-01

Bacterial vaginosis (BV) is the most common vaginal disorder among reproductive age women. One clinical indicator of BV is a "fishy" odor. This odor has been associated with increases in several biogenic amines (BAs) that may serve as important biomarkers. Within the vagina, BA production has been linked to various vaginal taxa, yet their genetic capability to synthesize BAs is unknown. Using a bioinformatics approach, we show that relatively few vaginal taxa are predicted to be capable of producing BAs. Many of these taxa (Dialister, Prevotella, Parvimonas, Megasphaera, Peptostreptococcus, and Veillonella spp.) are more abundant in the vaginal microbial community state type (CST) IV, which is depleted in lactobacilli. Several of the major Lactobacillus species (L. crispatus, L. jensenii, and L. gasseri) were identified as possessing gene sequences for proteins predicted to be capable of putrescine production. Finally, we show in a small cross sectional study of 37 women that the BAs putrescine, cadaverine and tyramine are significantly higher in CST IV over CSTs I and III. These data support the hypothesis that BA production is conducted by few vaginal taxa and may be important to the outgrowth of BV-associated (vaginal dysbiosis) vaginal bacteria.

Prevalence and risk factors associated with high-grade anal squamous intraepithelial lesions (HSIL)-AIN2 and HSIL-AIN3 in homosexual men.

PubMed

Machalek, Dorothy A; Jin, Fengyi; Poynten, I Mary; Hillman, Richard J; Templeton, David J; Law, Carmella; Roberts, Jennifer M; Tabrizi, Sepehr N; Garland, Suzanne M; Farnsworth, Annabelle; Fairley, Christopher K; Grulich, Andrew E

2016-12-01

Anal intraepithelial neoplasia grade 2 (AIN2) and AIN grade 3 (AIN3) are commonly grouped together as high grade squamous intraepithelial lesions (HSIL). We assessed risk factors for HSIL-AIN2 and HSIL-AIN3 in a cohort of homosexual men. At the baseline visit in the Study for the Prevention of Anal Cancer (SPANC), all men completed a questionnaire and underwent anal swabbing for cytology and HPV genotyping, followed by high resolution anoscopy. Composite-HSIL prevalence was 47% and 32% among 220 HIV-positive and 396 HIV-negative men, respectively. HSIL-AIN3 (37.7% versus 24.7%; p<0.001), but not HSIL-AIN2 (9.5% versus 7.6%; p=0.395) was more common in HIV-positive men. Recent receptive anal partners (p-trend=0.045), and increasing number of high-risk (HR)-HPV types (p-trend<0.001) were associated with HSIL-AIN2. Lifetime receptive partners (p-trend<0.001), HIV status (OR 1.74; 95% CI: 1.05-2.87) and HPV16 (OR 3.00; 95% CI: 1.56-5.75) were associated with HSIL-AIN3. HPV16 was the most common HR-HPV type detected in men with HSIL-AIN3, both HIV-negative (61.1%) and HIV-positive (54.9%). HPV16 was less commonly detected in men with HSIL-AIN2. Grouping HSIL-AIN2 and HSIL-AIN3 as HSIL may mask considerable heterogeneity in anal cancer risk. Given the strong link between HPV16 and anal cancer, men with HSIL-AIN3 and HPV16 are likely to be at greatest risk of cancer. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Vaginal bleeding in pregnancy

MedlinePlus

Pregnancy - vaginal bleeding; Maternal blood loss - vaginal ... Up to 1 in 4 women have vaginal bleeding at some time during their pregnancy. Bleeding is more common in the first 3 months (first trimester), especially with twins.

Vaginitis: diagnosis and management.

PubMed

Faro, S

1996-01-01

The various conditions that give rise to vaginitis include specific and nonspecific entities, such as candidiasis, trichomoniasis, bacterial vaginosis, group B streptococcal vaginitis, purulent vaginitis, volvodynia, and vestibulitis. The patient with chronic vaginitis usually develops this condition because of a misdiagnosis. It is critical that patients who have chronic vaginitis be thoroughly evaluated to determine if there is a specific etiology and whether their condition is recurrent or persistent, or is a reinfection. This also must include obtaining a detailed history, beginning with the patient's best recollection of when she felt perfectly normal. The physician must have an understanding of a healthy vaginal ecosystem and what mechanisms are in place to maintain the equilibrium. The vaginal ecosystem is a complex system of micro-organisms interacting with host factors to maintain its equilibrium. The endogenous microflora consists of a variety of bacteria, which include aerobic, facultative and obligate anaerobic bacteria. These organisms exist in a commensal, synergistic or antagonistic relationship. Therefore, it is important to understand what factors control the delicate equilibrium of the vaginal ecosystem, and which factors, both endogenous and exogenous, can disrupt this system. It is also important for the physician to understand that when a patient has symptoms of vaginitis it is not always due to an infectious etiology. There are situations in which an inflammatory reaction occurs but the specific etiology may not be determined. Thus, it is important that the physician not rush through the history or the examination.

Comparison between vaginal royal jelly and vaginal estrogen effects on quality of life and vaginal atrophy in postmenopausal women: a clinical trial study

PubMed Central

Seyyedi, Fatemeh; Kopaei, Mahmoud Rafiean; Miraj, Sepideh

2016-01-01

Objective This study was conducted to evaluate the therapeutic effects of vaginal royal jelly and vaginal estrogen on quality of life and vaginal atrophy in postmenopausal women. Methods This double-blind randomized controlled clinical trial was carried out at gynecology and obstetrics clinics of Hajar Hospital of Shahrekord University of Medical Sciences (Iran) from January 2013 to January 2014. The study was conducted on married postmenopausal women between 50 and 65 years old. Of 120 patients, 30 individuals were excluded based on the exclusion criteria, and 90 women were randomly distributed into three groups of 30 royal jelly vaginal cream 15%, vaginal Premarin, and placebo (lubricant), for three months. At the beginning and the end of the study, quality of life and vaginal cytology assay were evaluated. Data were analyzed by SPSS Version 11. Results Vaginal cream of royal jelly is significantly more effective than vaginal cream of Premarin and lubricant in improvement of quality of life in postmenopausal women (p<0.05). Moreover, Pap smear results showed that vaginal atrophy in vaginal Premarin group was lower than the other groups (p<0.001), and there was no significant difference between lubricant and royal jelly groups (p=0.89). Conclusion Administration of vaginal royal jelly was effective in quality-of-life improvement of postmenopausal women. Given to the various properties of royal jelly and its effectiveness on quality of life and vaginal atrophy in postmenopausal women, further studies are recommended for using =royal jelly in improving menopausal symptoms. Clinical trial registration The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT code: 2014112220043n1. Funding Shahrekord University of Medical Sciences supported this research (project no. 1440). PMID:28070251

Vaginal Cancer—Health Professional Version

Cancer.gov

Vaginal cancer is often squamous cell carcinoma. Other types of vaginal cancer are adenocarcinoma, melanoma, and sarcoma. Infection with certain types of human papillomavirus (HPV) causes most vaginal cancer. Find evidence-based information on vaginal cancer treatment and research.

Vaginal drug distribution modeling.

PubMed

Katz, David F; Yuan, Andrew; Gao, Yajing

2015-09-15

This review presents and applies fundamental mass transport theory describing the diffusion and convection driven mass transport of drugs to the vaginal environment. It considers sources of variability in the predictions of the models. It illustrates use of model predictions of microbicide drug concentration distribution (pharmacokinetics) to gain insights about drug effectiveness in preventing HIV infection (pharmacodynamics). The modeling compares vaginal drug distributions after different gel dosage regimens, and it evaluates consequences of changes in gel viscosity due to aging. It compares vaginal mucosal concentration distributions of drugs delivered by gels vs. intravaginal rings. Finally, the modeling approach is used to compare vaginal drug distributions across species with differing vaginal dimensions. Deterministic models of drug mass transport into and throughout the vaginal environment can provide critical insights about the mechanisms and determinants of such transport. This knowledge, and the methodology that obtains it, can be applied and translated to multiple applications, involving the scientific underpinnings of vaginal drug distribution and the performance evaluation and design of products, and their dosage regimens, that achieve it. Copyright © 2015 Elsevier B.V. All rights reserved.

Human papillomavirus genotype prevalence in cervical biopsies from women diagnosed with cervical intraepithelial neoplasia or cervical cancer in Fiji.

PubMed

Tabrizi, Sepehr N; Law, Irwin; Buadromo, Eka; Stevens, Matthew P; Fong, James; Samuela, Josaia; Patel, Mahomed; Mulholland, E Kim; Russell, Fiona M; Garland, Suzanne M

2011-09-01

There is currently limited information about human papillomavirus (HPV) genotype distribution in women in the South Pacific region. This study's objective was to determine HPV genotypes present in cervical cancer (CC) and precancers (cervical intraepithelial lesion (CIN) 3) in Fiji. Cross-sectional analysis evaluated archival CC and CIN3 biopsy samples from 296 women of Melanesian Fijian ethnicity (n=182, 61.5%) and Indo-Fijian ethnicity (n=114, 38.5%). HPV genotypes were evaluated using the INNO-LiPA assay in archival samples from CC (n=174) and CIN3 (n=122) among women in Fiji over a 5-year period from 2003 to 2007. Overall, 99% of the specimens tested were HPV DNA-positive for high-risk genotypes, with detection rates of 100%, 97.4% and 100% in CIN3, squamous cell carcinoma (SCC) and adenosquamous carcinoma biopsies, respectively. Genotypes 16 and 18 were the most common (77%), followed by HPV 31 (4.3%). Genotype HPV 16 was the most common identified (59%) in CIN3 specimens, followed by HPV 31 (9%) and HPV 52 (6.6%). Multiple genotypes were detected in 12.5-33.3% of specimens, depending on the pathology. These results indicated that the two most prevalent CC-associated HPV genotypes in Fiji parallel those described in other regions worldwide, with genotype variations thereafter. These data suggest that the currently available bivalent and quadrivalent HPV vaccines could potentially reduce cervical cancers in Fiji by over 80% and reduce precancers by at least 60%.

Vaginal Cancer

MedlinePlus

Vaginal cancer is a rare type of cancer. It is more common in women 60 and older. You are also more likely to get it if you have had a human ... test can find abnormal cells that may be cancer. Vaginal cancer can often be cured in its ...

The effect of vaginal cream containing ginger in users of clotrimazole vaginal cream on vaginal candidiasis.

PubMed

Shabanian, Sheida; Khalili, Sima; Lorigooini, Zahra; Malekpour, Afsaneh; Heidari-Soureshjani, Saeid

2017-01-01

Vulvovaginal candidiasis is one of the most common infections of the genital tract in women that causes many complications. Therefore, we examined the clinical effect of ginger cream along with clotrimazole compared to vaginal clotrimazole alone in this study. This double-blind clinical trial was conducted on 67 women admitted to the Gynecology Clinic of Hajar Hospital with vaginal candidiasis. The patients were divided randomly into two groups of 33 and 34 people. The diagnosis was made according to clinical symptoms, wet smear, and culture. Ginger-clotrimazole vaginal cream 1% and clotrimazole vaginal cream 1% were administered to groups 1 and 2, respectively, once a day for 7 days and therapeutic effects and symptoms were evaluated in readmission. Data analysis was performed using SPSS version 22, t -test and Chi-square. The mean value of variables itching ( P > 0.05), burning ( P > 0.05), and cheesy secretion ( P < 0.05) in users of ginger-clotrimazole was less than the other group after the treatment. Recurrence in clotrimazole group was 48.5% and in ginger-clotrimazole group 51.2% during the 1-month follow-up with no significant difference. Study results showed that cream containing ginger and clotrimazole 1% was more effective and may be more useful than the clotrimazole to treat vaginal candidiasis.

Vaginal mucosal flap as a sling preservation for the treatment of vaginal exposure of mesh.

PubMed

Kim, Sea Young; Park, Jong Yeon; Kim, Han Kwon; Park, Chang Hoo; Kim, Sung Jin; Sung, Gi Teck; Park, Chang Myon

2010-06-01

Tension-free vaginal tape (TVT) procedures are used for the treatment of stress urinary incontinence in women. The procedures with synthetic materials can have a risk of vaginal erosion. We experienced transobturator suburethral sling (TOT) tape-induced vaginal erosion and report the efficacy of a vaginal mucosal covering technique. A total of 560 female patients diagnosed with stress urinary incontinence underwent TOT procedures at our hospital between January 2005 and August 2009. All patients succeeded in follow-ups, among which 8 patients (mean age: 50.5 years) presented with vaginal exposure of the mesh. A vaginal mucosal covering technique was performed under local anesthesia after administration of antibiotics and vaginal wound dressings for 3-4 days. Seven of the 8 patients complained of persistent vaginal discharge postoperatively. Two of the 8 patients complained of dyspareunia of their male partners. The one remaining patient was otherwise asymptomatic, but mesh erosion was discovered at the routine follow-up visit. Six of the 8 patients showed complete mucosal covering of the mesh after the operation (mean follow-up period: 16 moths). Vaginal mucosal erosion recurred in 2 patients, and the mesh was then partially removed. One patient had recurrent stress urinary incontinence. Vaginal mucosal covering as a sling preservation with continued patient continence may be a feasible and effective option for the treatment of vaginal exposure of mesh after TOT tape procedures.

Prostate Cancer—Health Professional Version

Cancer.gov

Prostate cancers are often adenocarcinomas. Prostatic intraepithelial neoplasia is often present in association with prostatic adenocarcinoma. Find evidence-based information on prostate cancer including treatment, causes and prevention, screening, research, genetics, and statistics.

Distinguishing rhinitis and nasal neoplasia by radiography.

PubMed

Russo, M; Lamb, C R; Jakovljevic, S

2000-01-01

To compare the incidence of radiographic signs in dogs with rhinitis and primary nasal neoplasia and to assess the performance of observers for distinguishing these conditions, the nasal radiographs of 72 dogs with either rhinitis (n = 42) or primary nasal neoplasia (n = 30) were examined by two independent observers using custom-designed forms to record their interpretations. Rhinitis was associated with a higher incidence of focal or multifocal lesions, localised soft tissue opacities, lucent foci, and a lack of frontal sinus involvement. Neoplasia was associated with soft tissue opacities and loss of turbinate detail that affected the entire ipsilateral nasal cavity, signs of invasion of the bones surrounding the nasal cavity, and soft tissue/fluid opacities within the ipsilateral frontal sinus. The signs with the highest positive predictive value (PPV) for rhinitis were absence of frontal sinus lesions and lucent foci in nasal cavity (PPV of each 82%), and invasion of surrounding bones for neoplasia (PPV 88%). There were no significant differences in the position of the lesion within the nasal cavity, incidence of unilateral versus bilateral lesions, calcified lesions, or absence of teeth. There was moderate agreement between observers about the diagnosis (kappa 0.59). Areas (SE) under ROC curves were 0.94 (0.03) and 0.96 (0.03) for observers A and B, respectively (not significantly different; P = 0.68). These results indicate a high accuracy for radiologists examining dogs with nasal diseases. Differentiation of rhinitis and nasal neoplasia should be based on finding combinations of radiologic signs that together have a high PPV. Differences in interpretation between experienced observers in this study suggest that certain signs are potential sources of error.

Recent Changes of Classification for Squamous Intraepithelial Lesions of the Head and Neck.

PubMed

Cho, Kyung-Ja; Song, Joon Seon

2018-05-18

- Interpretation of atypical squamous lesions of the head and neck has always been a nettlesome task for pathologists. Moreover, many different grading systems for squamous intraepithelial lesions have been proposed in past decades. The recent World Health Organization 2017 classification presents 2 types of 2-tier systems for laryngeal and oral precursor lesions. - To review the recent changes in classification and the clinical significance for squamous intraepithelial lesions of the head and neck. - Personal experience and data from the literature. - The 2-tier grading system for laryngeal dysplasia, presented by World Health Organization in 2017, is expected to improve diagnostic reproducibility and clinical implication. However, the diagnostic criteria for low-grade dysplasia do not distinguish it clearly from basal cell hyperplasia. The World Health Organization 2017 classification of oral epithelial dysplasia remains unclear, and complicated and variable grading systems still make head and neck intraepithelial lesions difficult to interpret.

Lactobacilli Dominance and Vaginal pH: Why Is the Human Vaginal Microbiome Unique?

PubMed

Miller, Elizabeth A; Beasley, DeAnna E; Dunn, Robert R; Archie, Elizabeth A

2016-01-01

The human vaginal microbiome is dominated by bacteria from the genus Lactobacillus , which create an acidic environment thought to protect women against sexually transmitted pathogens and opportunistic infections. Strikingly, lactobacilli dominance appears to be unique to humans; while the relative abundance of lactobacilli in the human vagina is typically >70%, in other mammals lactobacilli rarely comprise more than 1% of vaginal microbiota. Several hypotheses have been proposed to explain humans' unique vaginal microbiota, including humans' distinct reproductive physiology, high risk of STDs, and high risk of microbial complications linked to pregnancy and birth. Here, we test these hypotheses using comparative data on vaginal pH and the relative abundance of lactobacilli in 26 mammalian species and 50 studies ( N = 21 mammals for pH and 14 mammals for lactobacilli relative abundance). We found that non-human mammals, like humans, exhibit the lowest vaginal pH during the period of highest estrogen. However, the vaginal pH of non-human mammals is never as low as is typical for humans (median vaginal pH in humans = 4.5; range of pH across all 21 non-human mammals = 5.4-7.8). Contrary to disease and obstetric risk hypotheses, we found no significant relationship between vaginal pH or lactobacilli relative abundance and multiple metrics of STD or birth injury risk ( P -values ranged from 0.13 to 0.99). Given the lack of evidence for these hypotheses, we discuss two alternative explanations: the common function hypothesis and a novel hypothesis related to the diet of agricultural humans. Specifically, with regard to diet we propose that high levels of starch in human diets have led to increased levels of glycogen in the vaginal tract, which, in turn, promotes the proliferation of lactobacilli. If true, human diet may have paved the way for a novel, protective microbiome in human vaginal tracts. Overall, our results highlight the need for continuing research on non

Comparison of patient- and clinician-collected anal cytology samples to screen for human papillomavirus-associated anal intraepithelial neoplasia in men who have sex with men.

PubMed

Chin-Hong, Peter V; Berry, J Michael; Cheng, Su-Chun; Catania, Joseph A; Da Costa, Maria; Darragh, Teresa M; Fishman, Fred; Jay, Naomi; Pollack, Lance M; Palefsky, Joel M

2008-09-02

Human papillomavirus (HPV)-associated anal cancer is increasing in prevalence and is more common among men who have sex with men and HIV-positive individuals than cervical cancer is among women in the United States. Cytology screening can detect the anal cancer precursor, anal intraepithelial neoplasia (AIN). Little is known about self-collected samples for AIN screening, and few community-based AIN estimates exist. To compare the sensitivity of self-collected versus clinician-collected anal cytology specimens to detect biopsy-confirmed AIN and the prevalence estimate of AIN in a community sample. Cross-sectional study. Participants were mailed anal cytology self-collection kits with instructions. Clinicians repeated anal cytology and performed high-resolution anoscopy with biopsies as the diagnostic reference standard. San Francisco, California. Community-based sample of men who have sex with men. Prevalence of anal HPV and AIN. Sensitivity and specificity of self-collected and clinician-collected anal cytology specimens to diagnose AIN were calculated. Biopsy-proven AIN was diagnosed in 57% of HIV-positive and 35% of HIV-negative participants (P = 0.04), and 80% provided adequate self-collected specimens for interpretation. The sensitivity of cytology to detect AIN in HIV-positive men was 75% (95% CI, 51% to 93%) when self-collected and 90% (CI, 68% to 99%) when clinician-collected; respective values in HIV-negative men were 48% (CI, 26% to 70%) and 62% (CI, 38% to 82%). The specificity of cytology to detect AIN in HIV-positive men was 50% (CI, 22% to 78%) when self-collected and 64% (CI, 36% to 86%) when clinician-collected; respective values in HIV-negative men were 86% (CI, 71% to 94%) and 85% (CI, 72% to 93%). The study sample was from a narrowly defined geographical area. Participants self-reported HIV status. In a community-based sample, a high proportion of HIV-positive and HIV-negative men who have sex with men have AIN. The sensitivity of cytology to

Accuracy of reading liquid based cytology slides using the ThinPrep Imager compared with conventional cytology: prospective study

PubMed Central

d'Assuncao, Jefferson; Irwig, Les; Macaskill, Petra; Chan, Siew F; Richards, Adele; Farnsworth, Annabelle

2007-01-01

Objective To compare the accuracy of liquid based cytology using the computerised ThinPrep Imager with that of manually read conventional cytology. Design Prospective study. Setting Pathology laboratory in Sydney, Australia. Participants 55 164 split sample pairs (liquid based sample collected after conventional sample from one collection) from consecutive samples of women choosing both types of cytology and whose specimens were examined between August 2004 and June 2005. Main outcome measures Primary outcome was accuracy of slides for detecting squamous lesions. Secondary outcomes were rate of unsatisfactory slides, distribution of squamous cytological classifications, and accuracy of detecting glandular lesions. Results Fewer unsatisfactory slides were found for imager read cytology than for conventional cytology (1.8% v 3.1%; P<0.001). More slides were classified as abnormal by imager read cytology (7.4% v 6.0% overall and 2.8% v 2.2% for cervical intraepithelial neoplasia of grade 1 or higher). Among 550 patients in whom imager read cytology was cervical intraepithelial neoplasia grade 1 or higher and conventional cytology was less severe than grade 1, 133 of 380 biopsy samples taken were high grade histology. Among 294 patients in whom imager read cytology was less severe than cervical intraepithelial neoplasia grade 1 and conventional cytology was grade 1 or higher, 62 of 210 biopsy samples taken were high grade histology. Imager read cytology therefore detected 71 more cases of high grade histology than did conventional cytology, resulting from 170 more biopsies. Similar results were found when one pathologist reread the slides, masked to cytology results. Conclusion The ThinPrep Imager detects 1.29 more cases of histological high grade squamous disease per 1000 women screened than conventional cytology, with cervical intraepithelial neoplasia grade 1 as the threshold for referral to colposcopy. More imager read slides than conventional slides were

A prospective study of risk-based colposcopy demonstrates improved detection of cervical precancers.

PubMed

Wentzensen, Nicolas; Walker, Joan; Smith, Katie; Gold, Michael A; Zuna, Rosemary; Massad, L Stewart; Liu, Angela; Silver, Michelle I; Dunn, S Terence; Schiffman, Mark

2018-06-01

Sensitivity for detection of precancers at colposcopy and reassurance provided by a negative colposcopy are in need of systematic study and improvement. We sought to evaluate whether selecting the appropriate women for multiple targeted cervical biopsies based on screening cytology, human papillomavirus testing, and colposcopic impression could improve accuracy and efficiency of cervical precancer detection. In all, 690 women aged 18-67 years referred to colposcopy subsequent to abnormal cervical cancer screening results were included in the study (ClinicalTrials.gov: NCT00339989). Up to 4 cervical biopsies were taken during colposcopy to evaluate the incremental benefit of multiple biopsies. Cervical cytology, human papillomavirus genotyping, and colposcopy impression were used to establish up to 24 different risk strata. Outcomes for the primary analysis were cervical precancers, which included p16 + cervical intraepithelial neoplasia 2 and all cervical intraepithelial neoplasia 3 that were detected by colposcopy-guided biopsy during the colposcopy visit. Later outcomes in women without cervical intraepithelial neoplasia 2 + at baseline were abstracted from electronic medical records. The risk of detecting precancer ranged from 2-82% across 24 strata based on colposcopy impression, cytology, and human papillomavirus genotyping. The risk of precancer in the lowest stratum increased only marginally with multiple biopsies. Women in the highest-risk strata had risks of precancer consistent with immediate treatment. In other risk strata, multiple biopsies substantially improved detection of cervical precancer. Among 361 women with cervical intraepithelial neoplasia <2 at baseline, 195 (54%) had follow-up cytology or histology data with a median follow-up time of 508 days. Lack of detection of precancer at initial colposcopy that included multiple biopsies predicted low risk of precancer during follow-up. Risk assessment at the colposcopy visit makes identification of

Clothing factors and vaginitis.

PubMed

Heidrich, F E; Berg, A O; Bergman, J J

1984-10-01

Associations of clothing factors and vulvovaginal symptoms, signs, and microbiology were sought in 203 women seeking care at a university family medicine clinic. Clothing factors studied were use of panty hose, underwear for sleep, cotton lining panels, and pants vs skirts. Women wearing and not wearing panty hose had similar rates of vaginitis symptoms and signs, but yeast vaginitis was about three times more common among wearers. Relationships of other clothing factors to vaginitis were not found. Nonspecific vaginitis was not found to be related to clothing.

The interaction between vaginal microbiota, cervical length, and vaginal progesterone treatment for preterm birth risk.

PubMed

Kindinger, Lindsay M; Bennett, Phillip R; Lee, Yun S; Marchesi, Julian R; Smith, Ann; Cacciatore, Stefano; Holmes, Elaine; Nicholson, Jeremy K; Teoh, T G; MacIntyre, David A

2017-01-19

Preterm birth is the primary cause of infant death worldwide. A short cervix in the second trimester of pregnancy is a risk factor for preterm birth. In specific patient cohorts, vaginal progesterone reduces this risk. Using 16S rRNA gene sequencing, we undertook a prospective study in women at risk of preterm birth (n = 161) to assess (1) the relationship between vaginal microbiota and cervical length in the second trimester and preterm birth risk and (2) the impact of vaginal progesterone on vaginal bacterial communities in women with a short cervix. Lactobacillus iners dominance at 16 weeks of gestation was significantly associated with both a short cervix <25 mm (n = 15, P < 0.05) and preterm birth <34 +0  weeks (n = 18; P < 0.01; 69% PPV). In contrast, Lactobacillus crispatus dominance was highly predictive of term birth (n = 127, 98% PPV). Cervical shortening and preterm birth were not associated with vaginal dysbiosis. A longitudinal characterization of vaginal microbiota (<18, 22, 28, and 34 weeks) was then undertaken in women receiving vaginal progesterone (400 mg/OD, n = 25) versus controls (n = 42). Progesterone did not alter vaginal bacterial community structure nor reduce L. iners-associated preterm birth (<34 weeks). L. iners dominance of the vaginal microbiota at 16 weeks of gestation is a risk factor for preterm birth, whereas L. crispatus dominance is protective against preterm birth. Vaginal progesterone does not appear to impact the pregnancy vaginal microbiota. Patients and clinicians who may be concerned about "infection risk" associated with the use of a vaginal pessary during high-risk pregnancy can be reassured.

Effect of vaginal or systemic estrogen on dynamics of collagen assembly in the rat vaginal wall.

PubMed

Montoya, T Ignacio; Maldonado, P Antonio; Acevedo, Jesus F; Word, R Ann

2015-02-01

The objective of this study was to compare the effects of systemic and local estrogen treatment on collagen assembly and biomechanical properties of the vaginal wall. Ovariectomized nulliparous rats were treated with estradiol or conjugated equine estrogens (CEEs) either systemically, vaginal CEE, or vaginal placebo cream for 4 wk. Low-dose local CEE treatment resulted in increased vaginal epithelial thickness and significant vaginal growth without uterine hyperplasia. Furthermore, vaginal wall distensibility increased without compromise of maximal force at failure. Systemic estradiol resulted in modest increases in collagen type I with no change in collagen type III mRNA. Low-dose vaginal treatment, however, resulted in dramatic increases in both collagen subtypes whereas moderate and high dose local therapies were less effective. Consistent with the mRNA results, low-dose vaginal estrogen resulted in increased total and cross-linked collagen content. The inverse relationship between vaginal dose and collagen expression may be explained in part by progressive downregulation of estrogen receptor-alpha mRNA with increasing estrogen dose. We conclude that, in this menopausal rat model, local estrogen treatment increased total and cross-linked collagen content and markedly stimulated collagen mRNA expression in an inverse dose-effect relationship. High-dose vaginal estrogen resulted in downregulation of estrogen receptor-alpha and loss of estrogen-induced increases in vaginal collagen. These results may have important clinical implications regarding the use of local vaginal estrogen therapy and its role as an adjunctive treatment in women with loss of vaginal support. © 2015 by the Society for the Study of Reproduction, Inc.

Prostate Expression Databases: Gene Expression Resources for Comparative Studies of Prostate Carcinogenesis

DTIC Science & Technology

2008-01-01

lesions of low -grade prostatic intraepithelial neoplasia (PIN). Over time, osteopontin expressing dysplastic cells seemed to increase in number in high...neoplasia (PIN) lesions, not seen at 2.5 months, were mostly low grade at 12 months and then turning to an abundant combination of low -grade PIN...Prostate specific antigen (PSA) allows the diagnosis of low grade, localized PCa, that allows the physician to offer the patient several efficacious

Photodynamic Therapy for Gynecological Diseases and Breast Cancer

PubMed Central

Shishkova, Natashis; Kuznetsova, Olga; Berezov, Temirbolat

2012-01-01

Photodynamic therapy (PDT) is a minimally invasive and promising new method in cancer treatment. Cytotoxic reactive oxygen species (ROS) are generated by the tissue-localized non-toxic sensitizer upon illumination and in the presence of oxygen. Thus, selective destruction of a targeted tumor may be achieved. Compared with traditional cancer treatment, PDI has advantages including higher selectivity and lower rate of toxicity. The high degree of selectivity of the proposed method was applied to cancer diagnosis using fluorescence. This article reviews previous studies done on PDT treatment and photodetection of cervical intraepithelial neoplasia, vulvar intraepithelial neoplasia, ovarian and breast cancer, and PDT application in treating non-cancer lesions. The article also highlights the clinical responses to PDT, and discusses the possibility of enhancing treatment efficacy by combination with immunotherapy and targeted therapy. PMID:23691448

Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis

PubMed Central

Soler, Vincent José; Tran-Viet, Khanh-Nhat; Galiacy, Stéphane D; Limviphuvadh, Vachiranee; Klemm, Thomas Patrick; St Germain, Elizabeth; Fournié, Pierre R; Guillaud, Céline; Maurer-Stroh, Sebastian; Hawthorne, Felicia; Suarez, Cyrielle; Kantelip, Bernadette; Afshari, Natalie A; Creveaux, Isabelle; Luo, Xiaoyan; Meng, Weihua; Calvas, Patrick; Cassagne, Myriam; Arné, Jean-Louis; Rozen, Steven G; Malecaze, François; Young, Terri L

2014-01-01

Background Corneal intraepithelial dyskeratosis is an extremely rare condition. The classical form, affecting Native American Haliwa-Saponi tribe members, is called hereditary benign intraepithelial dyskeratosis (HBID). Herein, we present a new form of corneal intraepithelial dyskeratosis for which we identified the causative gene by using deep sequencing technology. Methods and results A seven member Caucasian French family with two corneal intraepithelial dyskeratosis affected individuals (6-year-old proband and his mother) was ascertained. The proband presented with bilateral complete corneal opacification and dyskeratosis. Palmoplantar hyperkeratosis and laryngeal dyskeratosis were associated with the phenotype. Histopathology studies of cornea and vocal cord biopsies showed dyskeratotic keratinisation. Quantitative PCR ruled out 4q35 duplication, classically described in HBID cases. Next generation sequencing with mean coverage of 50× using the Illumina Hi Seq and whole exome capture processing was performed. Sequence reads were aligned, and screened for single nucleotide variants and insertion/deletion calls. In-house pipeline filtering analyses and comparisons with available databases were performed. A novel missense mutation M77T was discovered for the gene NLRP1 which maps to chromosome 17p13.2. This was a de novo mutation in the proband’s mother, following segregation in the family, and not found in 738 control DNA samples. NLRP1 expression was determined in adult corneal epithelium. The amino acid change was found to destabilise significantly the protein structure. Conclusions We describe a new corneal intraepithelial dyskeratosis and how we identified its causative gene. The NLRP1 gene product is implicated in inflammation, autoimmune disorders, and caspase mediated apoptosis. NLRP1 polymorphisms are associated with various diseases. PMID:23349227

Secondary intracranial neoplasia in the dog: 177 cases (1986-2003).

PubMed

Snyder, J M; Lipitz, L; Skorupski, K A; Shofer, F S; Van Winkle, T J

2008-01-01

This study investigates the frequency, location, and clinical findings associated with 177 secondary brain tumors in dogs. Secondary intracranial neoplasia is more common than primary intracranial neoplasia in dogs during the time period studied, and hemangiosarcoma (HSA) is the most common secondary intracranial tumor. One hundred and seventy-seven client-owned dogs presented to the Matthew J. Ryan Veterinary Hospital between 1986 and 2003. Medical records were searched for a diagnosis of intracranial neoplasia in dogs who underwent complete postmortem examination. Of these dogs, those with a diagnosis of primary intracranial neoplasia were excluded. Of the 177 secondary brain tumors, 51 (29%) were HSAs, 44 (25%) were pituitary tumors, 21 (12%) were lymphosarcomas, and 21 (12%) were metastatic carcinomas. The average age at diagnosis was 9.6 +/- 3.0 years. Most tumors were located in the cerebrum, and a mentation change was the most common presenting clinical sign. On postmortem examination, the same tumor that was in the brain was also present in the lung in 84 cases (47%), in the kidney in 62 cases (35%), and in the heart in 55 cases (31%). Secondary intracranial neoplasia in dogs was more common than primary intracranial neoplasia during the time period studied. Many of these dogs had related disease in other body systems that was apparent on diagnostic tests such as thoracic radiography.

Assisted Vaginal Delivery

MedlinePlus

... Patient Education FAQs Assisted Vaginal Delivery Patient Education Pamphlets - Spanish Assisted Vaginal Delivery FAQ192, February 2016 PDF ... on Patient Safety For Patients Patient FAQs Spanish Pamphlets Teen Health About ACOG About Us Leadership & Governance ...

Vaginal estrogen: a dual-edged sword in postoperative healing of the vaginal wall.

PubMed

Ripperda, Christopher M; Maldonado, Pedro Antonio; Acevedo, Jesus F; Keller, Patrick W; Akgul, Yucel; Shelton, John M; Word, Ruth Ann

2017-07-01

Reconstructive surgery for pelvic organ prolapse is plagued with high failure rates possibly due to impaired healing or regeneration of the vaginal wall. Here, we tested the hypothesis that postoperative administration of local estrogen, direct injection of mesenchymal stem cells (MSCs), or both lead to improved wound healing of the injured vagina in a menopausal rat model. Ovariectomized rats underwent surgical injury to the posterior vaginal wall and were randomized to treatment with placebo (n = 41), estrogen cream (n = 47), direct injection of MSCs (n = 39), or both (n = 43). MSCs did not survive after injection and had no appreciable effects on healing of the vaginal wall. Acute postoperative administration of vaginal estrogen altered the response of the vaginal wall to injury with decreased stiffness, decreased collagen content, and decreased expression of transcripts for matrix components in the stromal compartment. Conversely, vaginal estrogen resulted in marked proliferation of the epithelial layer and increased expression of genes related to epithelial barrier function and protease inhibition. Transcripts for genes involved in chronic inflammation and adaptive immunity were also down-regulated in the estrogenized epithelium. Collectively, these data indicate that, in contrast to the reported positive effects of preoperative estrogen on the uninjured vagina, acute administration of postoperative vaginal estrogen has adverse effects on the early phase of healing of the stromal layer. In contrast, postoperative estrogen plays a positive role in healing of the vaginal epithelium after injury.

Vaginal estrogen: a dual-edged sword in postoperative healing of the vaginal wall

PubMed Central

Ripperda, Christopher M.; Maldonado, Pedro Antonio; Acevedo, Jesus F.; Keller, Patrick W.; Akgul, Yucel; Shelton, John M.; Word, Ruth Ann

2017-01-01

Abstract Objective: Reconstructive surgery for pelvic organ prolapse is plagued with high failure rates possibly due to impaired healing or regeneration of the vaginal wall. Here, we tested the hypothesis that postoperative administration of local estrogen, direct injection of mesenchymal stem cells (MSCs), or both lead to improved wound healing of the injured vagina in a menopausal rat model. Methods: Ovariectomized rats underwent surgical injury to the posterior vaginal wall and were randomized to treatment with placebo (n = 41), estrogen cream (n = 47), direct injection of MSCs (n = 39), or both (n = 43). Results: MSCs did not survive after injection and had no appreciable effects on healing of the vaginal wall. Acute postoperative administration of vaginal estrogen altered the response of the vaginal wall to injury with decreased stiffness, decreased collagen content, and decreased expression of transcripts for matrix components in the stromal compartment. Conversely, vaginal estrogen resulted in marked proliferation of the epithelial layer and increased expression of genes related to epithelial barrier function and protease inhibition. Transcripts for genes involved in chronic inflammation and adaptive immunity were also down-regulated in the estrogenized epithelium. Conclusions: Collectively, these data indicate that, in contrast to the reported positive effects of preoperative estrogen on the uninjured vagina, acute administration of postoperative vaginal estrogen has adverse effects on the early phase of healing of the stromal layer. In contrast, postoperative estrogen plays a positive role in healing of the vaginal epithelium after injury. PMID:28169915

Human papillomavirus is associated with the frequent detection of warty and basaloid high-grade neoplasia of the vulva and cervical neoplasia among immunocompromised women.

PubMed

Petry, K U; Köchel, H; Bode, U; Schedel, I; Niesert, S; Glaubitz, M; Maschek, H; Kühnle, H

1996-01-01

A total of 158 women who either HIV-infected or under iatrogenic immunosuppression were examined regularly during a 4-year period to evaluate if certain vulvar neoplasms and cervical neoplasia have similar associated risk factors. Patients with CIN were matched prospectively with immunocompetent controls with CIN. Forty-eight cervical lesions were detected among patients, including 2 invasive carcinoma and 15 CIN-3 lesions, compared to 11 vulvar lesions, including 2 invasive carcinoma and 7 VIN-3 lesions. Women who have more than five life-time partners were more likely to have HPV-DNA positive cervical swabs and vulvar scrapes as well as cervical and/or vulvar neoplasia. Compared to 2.7% of controls 15.2% of patients with CIN had coexisting high-grade lesions of the vulva. With 1 exception all patients with vulvar neoplasia either suffered from symptomatic immunodeficiency or received immunosuppressive drugs for more than 10 years. Except for 1 VIN-3 lesions, all vulvar neoplasms were associated with HPV-DNA types 16, 31, and/or 33. Six of nine patients as well as the 2 controls with coexisting vulvar and cervical neoplasia had the same HPV-type associated with both lesions. All vulvar lesions were classified as either "warty" or "basaloid". In conclusion cervical and bowenoid/basaloid vulvar neoplasia seem to have a similar HPV-related genesis. Malfunction of the cellular immune response appears to be a cofactor in the genesis of HPV-associated neoplasia at both sites.

Lactobacilli Dominance and Vaginal pH: Why Is the Human Vaginal Microbiome Unique?

PubMed Central

Miller, Elizabeth A.; Beasley, DeAnna E.; Dunn, Robert R.; Archie, Elizabeth A.

2016-01-01

The human vaginal microbiome is dominated by bacteria from the genus Lactobacillus, which create an acidic environment thought to protect women against sexually transmitted pathogens and opportunistic infections. Strikingly, lactobacilli dominance appears to be unique to humans; while the relative abundance of lactobacilli in the human vagina is typically >70%, in other mammals lactobacilli rarely comprise more than 1% of vaginal microbiota. Several hypotheses have been proposed to explain humans' unique vaginal microbiota, including humans' distinct reproductive physiology, high risk of STDs, and high risk of microbial complications linked to pregnancy and birth. Here, we test these hypotheses using comparative data on vaginal pH and the relative abundance of lactobacilli in 26 mammalian species and 50 studies (N = 21 mammals for pH and 14 mammals for lactobacilli relative abundance). We found that non-human mammals, like humans, exhibit the lowest vaginal pH during the period of highest estrogen. However, the vaginal pH of non-human mammals is never as low as is typical for humans (median vaginal pH in humans = 4.5; range of pH across all 21 non-human mammals = 5.4–7.8). Contrary to disease and obstetric risk hypotheses, we found no significant relationship between vaginal pH or lactobacilli relative abundance and multiple metrics of STD or birth injury risk (P-values ranged from 0.13 to 0.99). Given the lack of evidence for these hypotheses, we discuss two alternative explanations: the common function hypothesis and a novel hypothesis related to the diet of agricultural humans. Specifically, with regard to diet we propose that high levels of starch in human diets have led to increased levels of glycogen in the vaginal tract, which, in turn, promotes the proliferation of lactobacilli. If true, human diet may have paved the way for a novel, protective microbiome in human vaginal tracts. Overall, our results highlight the need for continuing research on non

Impact of human papillomavirus (HPV) 16 and 18 vaccination on prevalent infections and rates of cervical lesions after excisional treatment

PubMed Central

Hildesheim, Allan; Gonzalez, Paula; Kreimer, Aimee R.; Wacholder, Sholom; Schussler, John; Rodriguez, Ana C.; Porras, Carolina; Schiffman, Mark; Sidawy, Mary; Schiller, John T.; Lowy, Douglas R.; Herrero, Rolando

2016-01-01

BACKGROUND Human papillomavirus (HPV) vaccines prevent HPV infection and cervical precancers. The impact of vaccinating women with a current infection or after treatment for an HPV-associated lesion is not fully understood. OBJECTIVES To determine whether HPV-16/18 vaccination influences the outcome of infections present at vaccination and the rate of infection and disease after treatment of lesions. STUDY DESIGN We included 1711 women (18–25 years) with carcinogenic human papillomavirus infection and 311 women of similar age who underwent treatment for cervical precancer and who participated in a community-based trial of the AS04-adjuvanted HPV-16/18 virus-like particle vaccine. Participants were randomized (human papillomavirus or hepatitis A vaccine) and offered 3 vaccinations over 6 months. Follow-up included annual visits (more frequently if clinically indicated), referral to colposcopy of high-grade and persistent low-grade lesions, treatment by loop electrosurgical excisional procedure when clinically indicated, and cytologic and virologic follow-up after treatment. Among women with human papillomavirus infection at the time of vaccination, we considered type-specific viral clearance, and development of cytologic (squamous intraepithelial lesions) and histologic (cervical intraepithelial neoplasia) lesions. Among treated women, we considered single-time and persistent human papillomavirus infection, squamous intraepithelial lesions, and cervical intraepithelial neoplasia 2+. Outcomes associated with infections absent before treatment also were evaluated. Infection-level analyses were performed and vaccine efficacy estimated. RESULTS Median follow-up was 56.7 months (women with human papillomavirus infection) and 27.3 months (treated women). There was no evidence of vaccine efficacy to increase clearance of human papillomavirus infections or decrease incidence of cytologic/histologic abnormalities associated with human papillomavirus types present at

p16 Is Superior to ProEx C in Identifying High-grade Squamous Intraepithelial Lesions (HSIL) of the Anal Can

PubMed Central

Bala, Rajeev; Pinsky, Benjamin A.; Beck, Andrew H.; Kong, Christina S.; Welton, Mark L.; Longacre, Teri A.

2016-01-01

Although the incidence of human papillomavirus (HPV)-associated anal neoplasia is increasing, interobserver and intraobserver reproducibility in the grading of biopsy specimens from this area remains unacceptably low. Attempts to produce a more reproducible grading scheme have led to the use of biomarkers for the detection of high-risk HPV (HR-HPV). We evaluated the performance of standard morphology and biomarkers p16, ProEx C, and Ki-67 in a set of 75 lesions [17 nondysplastic lesions, 23 low-grade squamous intraepithelial lesions (LSIL)/condyloma, 20 high-grade squamous intraepithelial lesions (HSIL), 15 invasive squamous cell carcinomas] from the anal and perianal region in 65 patients and correlated these findings with HPV subtype on the basis of a type-specific multiplex real-time polymerase chain reaction assay designed to detect HR-HPV. A subset of cases with amplifiable HPV DNA was also sequenced. HSIL was typically flat (15/20), and only a minority (4/20) had koilocytes. In contrast, only 1 LSIL was flat (1/23), and the remainder were exophytic. The majority of LSIL had areas of koilocytic change (20/23). HR-HPV DNA was detected in the majority (89%) of invasive carcinomas and HSIL biopsies, 86% and 97% of which were accurately labeled by strong and diffuse block-positive p16 and ProEx C, respectively. LSIL cases, however, only infrequently harbored HR-HPV (13%); most harbored low-risk HPV (LR-HPV) types 6 and 11. Within the LSIL group, p16 outperformed ProEx C, resulting in fewer false-positive cases (5% vs. 75%). Ki-67 was also increased in HR-HPV-positive lesions, although biopsies with increased inflammation and reactive changes also showed higher Ki-67 indices. These data suggest that strong and diffuse block-positive nuclear and cytoplasmic labeling with p16 is a highly specific biomarker for the presence of HR-HPV in anal biopsies and that this finding correlates with high-grade lesions. PMID:23552383

Evolving concepts in the management of lobular neoplasia.

PubMed

Anderson, Benjamin O; Calhoun, Kristine E; Rosen, Eric L

2006-05-01

Lobular neoplasia broadly defines the spectrum of changes within the lobule, ranging from atypical lobular hyperplasia (ALH) to lobular carcinoma in situ (LCIS). This continuum of lesions is associated with an increased risk for developing subsequent invasive breast cancer, with the magnitude of that risk corresponding to the degree of proliferative change. The associated risk for developing invasive breast cancer after a diagnosis of lobular neoplasia is multicentric, bilateral, and equal in both breasts. Lobular neoplasia itself may transform into invasive carcinoma, although the frequency of this occurrence is unknown. Thus, lobular neoplasia is a risk factor for invasive breast cancer and may be a precursor lesion in unusual circumstances. The management of ALH and LCIS depends on the setting in which they are encountered. When ALH and LCIS are diagnosed after core needle breast biopsy, wire localization for surgical excision is required for definitive diagnosis because rates of histologic underestimation approach those of atypical ductal hyperplasia (ADH). When diagnosed on surgical biopsy, ALH and LCIS generally do not require further intervention, even when present at a surgical margin. However, bilateral breast cancer risk must be considered, especially when patients have a family history of breast cancer. In selected situations, bilateral prophylactic mastectomy with or without reconstruction may be considered when atypical hyperplasia or LCIS is diagnosed. Although this reduces risk for developing subsequent breast carcinoma by 90%, patients selected for prophylactic mastectomy represent a small subgroup of lobular neoplasia patients and generally have other risk factors, such as strong family history or evidence of genetic predisposition.

True vaginal prolapse in a bitch.

PubMed

Alan, M; Cetin, Y; Sendag, S; Eski, F

2007-08-01

Frequently, vaginal fold prolapse is the protrusion of edematous vaginal tissue into and through the opening of the vulva occurring during proestrus and estrus stages of the sexual cycle. True vaginal prolapse may occur near parturition, as the concentration of serum progesterone declines and the concentration of serum oestrogen increases. In the bitch, this type of true vaginal prolapse is a very rare condition. This short communication describes a 5-year-old female, cross-breed dog in moderate condition, weighing 33 kg, with distocia and true vaginal prolapse. Abdominal palpation and transabdominal ultrasonography revealed live and dead foetuses in the uterine horns. One dead and four live fetuses were removed from uterus by cesarean section. The ovariohysterectomy was performed after repositioning the vaginal wall with a combination of traction from within the abdomen and external manipulation through the vulva. Re-occurrence of a vaginal prolapse was not observed and the bitch recovered completely after the surgical therapy. Compared to other vaginal disorders, vaginal prolapse is an uncommon condition in the bitch. In the present case, extreme tenesmus arising from distocia may have predisposed to the vaginal prolapse. The cause of dystocia was probably the disposition of the first foetus. We concluded that the vaginal prolapse was the result of dystocia in the present case.

Dinoprostone vaginal insert versus intravenous oxytocin to reduce postpartum blood loss following vaginal or cesarean delivery.

PubMed

Ozalp, E; Tanir, H M; Sener, T

2010-01-01

To compare the impact of a dinoprostone vaginal insert and intravenous oxytocin in reducing blood loss of women undergoing vaginal or cesarean delivery. This study was conducted among term singleton pregnancies delivered vaginally or by elective cesarean section. In the vaginally delivered cases, active management of the third stage of labor was conducted. During cesarean delivery, 20 IU of intravenous oxytocin was administered. Women, who either delivered via the vaginal or abdominal route, were then randomly allocated to receive 10 mg vaginal dinoprostone insert for 12 hours (group I, n: 100) or intravenous oxytocin (group II, n: 100), respectively. Mean blood loss and need for additional uterotonics and postpartum hemoglobin and hematocrit levels at 24 and 36 hours after delivery did not differ between the two groups. Women allocated to the dinoprostone vaginal insert arm experienced more nausea and vomiting. Dinoprostone vaginal insert was as effective as intravenous oxytocin in the prevention of postpartum blood loss.

Evaluation of vaginal complaints.

PubMed

Anderson, Matthew R; Klink, Kathleen; Cohrssen, Andreas

2004-03-17

Vaginal symptoms are one of the most common reasons for gynecological consultation. Clinicians have traditionally diagnosed vaginal candidiasis, bacterial vaginosis, and vaginal trichomoniasis using some combination of physical examination, pH, the wet mount, and the whiff test. To evaluate the role of the clinical examination and determine the positive and negative likelihood ratios (LRs) for the diagnosis of vaginal candidiasis, bacterial vaginosis, and vaginal trichomoniasis. Using a structured literature review, we abstracted information on sensitivity and specificity for symptoms, signs, and office laboratory procedures. We chose published (1966 to April 2003) articles that appeared in the MEDLINE database and were indexed under the combined search terms of diagnosis with vaginitis, vaginal discharge, candidiasis, bacterial vaginosis, and trichomoniasis. Included studies of symptomatic premenopausal women seen in primary care settings. Tests were evaluated only if they would provide diagnostic information during the office visit and were compared with an acceptable criterion standard. All 3 authors extracted the data and computed sensitivity and specificity from each article independently. The absence of standard definitions for symptoms and signs made it impossible to combine results across studies. Symptoms alone do not allow clinicians to distinguish confidently between the causes of vaginitis. However, a patient's lack of itching makes candidiasis less likely (range of LRs, 0.18 [95% confidence interval [CI], 0.05-0.70] to 0.79 [95% CI, 0.72-0.87]) and lack of perceived odor makes bacterial vaginosis unlikely (LR, 0.07 [95% CI, 0.01-0.51]). Similarly, physical examination signs are limited in their diagnostic power. The presence of inflammatory signs is associated with candidiasis (range of LRs, 2.1 [95% CI, 1.5-2.8] to 8.4 [95% CI, 2.3-31]). Presence of a "high cheese" odor on examination is predictive of bacterial vaginosis (LR, 3.2 [95% CI, 2

The Association between HIV Infection, Antiretroviral Therapy and Cervical Squamous Intraepithelial Lesions in South Western Nigerian Women

PubMed Central

Ezechi, Oliver Chukwujekwu; Pettersson, Karen Odberg; Okolo, Clement Abu; Ujah, Innocent Achaya O.; Ostergren, Per Olof

2014-01-01

Introduction Findings from studies that evaluated the effect of antiretroviral drug use on the development of cervical squamous intraepithelial lesion differed in their conclusions. This study investigated the association between HIV infection, antiretroviral drug use and cervical squamous intraepithelial lesion in a high HIV and cervical cancer burden setting- Nigeria. Methods A cross sectional study among 1140 women of known HIV status enrolled in a randomised study to determine the test characteristics of visual inspection in detecting cytology diagnosed squamous intraepithelial lesion. Multivariate analysis was used to determine the association between HIV infection, antiretroviral drug use and the twin outcome variables of cervical squamous intraepithelial lesion (SIL) and High grade squamous intraepithelial lesion (HSIL) while controlling for confounders. Results Prevalence of cervical squamous intraepithelial lesion was 8.5%, with a higher prevalence of 14.3% in HIV positive compared to 3.3% in HIV negative women (aOR: 5.4; 95% CI: 2.9–8.8). Not using antiretroviral drugs was found to be associated with an increased risk of SIL (aOR: 2.1; 95% CI: 1.4–3.5) and HSIL (aOR: 2.6; 95% CI: 1.1–6.4). Participants who had a CD4 cell count <200 cells/mm3, were also found to be at increased risk for SIL (aOR: 1.9; 95% CI: 1.1–5.9) and HSIL (aOR: 5.7; 95% CI: 1.1–7.2). Conclusion HIV infection and severe immunosuppression were found to be associated with increased risk of cervical squamous intraepithelial lesion but not viral load. For the first time, in the West African sub-region with specific HIV type and strains, we established the protective effect of antiretroviral drug use against the development of SIL. Integration of cervical cancer screening programme into HIV services and early initiation of antiretroviral drug in HIV positive women especially those with severe immune-suppression could therefore prove to be useful in preventing and controlling

Management of vaginal extrusion after tension-free vaginal tape procedure for urodynamic stress incontinence.

PubMed

Giri, Subhasis K; Sil, Debasri; Narasimhulu, Girish; Flood, Hugh D; Skehan, Mark; Drumm, John

2007-06-01

To report our experience in the management of vaginal extrusion after the tension-free vaginal tape (TVT) procedure for urodynamic stress incontinence. Five patients diagnosed with vaginal extrusion after a TVT procedure performed at our institution were identified. We reviewed the patients' records retrospectively. The interval from TVT placement to diagnosis, presenting symptoms and signs, duration of symptoms, diagnostic test findings, treatment, and postoperative results were recorded. Patients were followed up for at least 12 months. From January 2001 to June 2004, a total of 166 patients underwent the TVT procedure. Of these, 5 patients (3%) were diagnosed with isolated vaginal extrusion 4 to 40 months postoperatively. No cases of urethral or bladder erosion occurred in this series. The symptoms included vaginal discharge, pain, bleeding, and dyspareunia. The eroded margin of the vaginal mucosa was trimmed, mobilized, and closed over the tape with interrupted vertical mattress sutures in a single layer using 2-0 polyglactin 910 to avoid mucosal inversion. All patients remained symptom free without any evidence of defective healing or additional extrusion at a minimal follow-up of 12 months. Primary reclosure of the vaginal mucosa over the TVT tape is an effective first-line treatment option for vaginal extrusion without compromising continence. Patients undergoing the TVT procedure should be adequately counseled about the possibility of this complication and the available treatment options.

Vaginitis: current microbiologic and clinical concepts.

PubMed Central

Hill, L V; Embil, J A

1986-01-01

Infectious vaginitis occurs when the normal vaginal flora is disrupted; it may arise when saprophytes overwhelm the host immune response, when pathogenic organisms are introduced into the vagina or when changes in substrate allow an imbalance of microorganisms to develop. Examples of these types of vaginitis include the presence of chronic fungal infection in women with an inadequate cellular immune response to the yeast, the introduction of trichomonads into vaginal epithelium that has a sufficient supply of glycogen, and the alteration in bacterial flora, normally dominated by Lactobacillus spp., and its metabolites that is characteristic of "nonspecific vaginitis". The authors review microbiologic and clinical aspects of the fungal, protozoal and bacterial infections, including the interactions of bacteria thought to produce nonspecific vaginitis, that are now recognized as causing vaginitis. Other causes of vaginitis are also discussed. PMID:3510698

Vaginitis: current microbiologic and clinical concepts.

PubMed

Hill, L V; Embil, J A

1986-02-15

Infectious vaginitis occurs when the normal vaginal flora is disrupted; it may arise when saprophytes overwhelm the host immune response, when pathogenic organisms are introduced into the vagina or when changes in substrate allow an imbalance of microorganisms to develop. Examples of these types of vaginitis include the presence of chronic fungal infection in women with an inadequate cellular immune response to the yeast, the introduction of trichomonads into vaginal epithelium that has a sufficient supply of glycogen, and the alteration in bacterial flora, normally dominated by Lactobacillus spp., and its metabolites that is characteristic of "nonspecific vaginitis". The authors review microbiologic and clinical aspects of the fungal, protozoal and bacterial infections, including the interactions of bacteria thought to produce nonspecific vaginitis, that are now recognized as causing vaginitis. Other causes of vaginitis are also discussed.

Effect of Vaginal or Systemic Estrogen on Dynamics of Collagen Assembly in the Rat Vaginal Wall1

PubMed Central

Montoya, T. Ignacio; Maldonado, P. Antonio; Acevedo, Jesus F.; Word, R. Ann

2014-01-01

ABSTRACT The objective of this study was to compare the effects of systemic and local estrogen treatment on collagen assembly and biomechanical properties of the vaginal wall. Ovariectomized nulliparous rats were treated with estradiol or conjugated equine estrogens (CEEs) either systemically, vaginal CEE, or vaginal placebo cream for 4 wk. Low-dose local CEE treatment resulted in increased vaginal epithelial thickness and significant vaginal growth without uterine hyperplasia. Furthermore, vaginal wall distensibility increased without compromise of maximal force at failure. Systemic estradiol resulted in modest increases in collagen type I with no change in collagen type III mRNA. Low-dose vaginal treatment, however, resulted in dramatic increases in both collagen subtypes whereas moderate and high dose local therapies were less effective. Consistent with the mRNA results, low-dose vaginal estrogen resulted in increased total and cross-linked collagen content. The inverse relationship between vaginal dose and collagen expression may be explained in part by progressive downregulation of estrogen receptor-alpha mRNA with increasing estrogen dose. We conclude that, in this menopausal rat model, local estrogen treatment increased total and cross-linked collagen content and markedly stimulated collagen mRNA expression in an inverse dose-effect relationship. High-dose vaginal estrogen resulted in downregulation of estrogen receptor-alpha and loss of estrogen-induced increases in vaginal collagen. These results may have important clinical implications regarding the use of local vaginal estrogen therapy and its role as an adjunctive treatment in women with loss of vaginal support. PMID:25537371

Directed shift of vaginal microbiota induced by vaginal application of sucrose gel in rhesus macaques.