Primary Anal Cancer Screening Results From 381 Women With Human Immunodeficiency Virus.

BACKGROUND: Women with human immunodeficiency virus (WWH) have an elevated risk for human papillomavirus (HPV)-associated anal cancer. Primary anal cancer screening results from this population could inform practice guidelines. METHODS: In total, 381 WWH with anal cytology screening, high-risk HPV (hrHPV) testing and genital (cervical or vaginal) cotesting within 6 months were identified during 2012-2019. Those with anal cytology of atypical squamous cells of undetermined significance (ASCUS) or worse underwent high-resolution anoscopy and biopsy. Independent predictors of anal hrHPV, HPV16, and histological anal high-grade squamous intraepithelial lesions (aHSIL) were identified using adjusted logistic regression models. RESULTS: Prevalence of anal hrHPV, HPV16, and ASCUS or worse cytology was 61%, 13%, and 68%. Histological aHSIL was detected in 42% of WWH with ASCUS or worse anal cytology. Prevalence of genital hrHPV, HPV16, and ASCUS or worse cytology was 30%, 4%, and 28%. Genital hrHPV predicted anal hrHPV (odds ratio [OR], 5.05), while genital HPV16 predicted anal HPV16 (OR, 9.52). Genital hrHPV and anal HPV16 predicted histological aHSIL (ORs, 2.78 and 10.9). CONCLUSIONS: Anal HPV disease was highly prevalent in this primary screening cohort of WWH. While genital screening results predicted anal disease, rates of isolated anal HPV disease were substantial, supporting universal anal cancer screening for this population.

Five-millimeter balloon trocar site herniation: report of two cases and review of literature.

Trocar site herniation is a well-known potential complication of minimally invasive surgery. We present the cases of two herniations after use of 5-mm non-bladed balloon trocars. In both patients, surgical management was required, with no subsequent sequelae to date. The hernias were attributed to excessive fascial stretching and compression by the balloon. We recommend full-thickness closure of 5-mm ports if a balloon is used or if there was extensive intraoperative manipulation.

Molecular alterations in uterine serous carcinoma.

OBJECTIVE: Uterine serous carcinoma (USC) is an aggressive endometrial cancer associated with poor prognosis despite comprehensive surgical staging and adjuvant chemotherapy and radiation therapy. Biologic targets have yet to be fully explored in this disease and research on such targets could lead to clinical trials utilizing a new class of therapeutics. METHODS: A MEDLINE search of molecular alterations in USC was performed and reviewed. RESULTS: Studies evaluating primary USC tumors for molecular alterations have focused on molecules such as the transmembrane receptor ERBB2 (HER-2), the epidermal growth factor receptor (EGFR), and the recently characterized oncogene PIK3CA, which encodes the catalytic p110-alpha subunit of phosphatidylinositol 3-kinase (PI3K). In addition, claudin-3 and claudin-4 have recently been shown to be highly expressed in USC and have potential utilization as tumor markers and possible target proteins. CONCLUSIONS: Since optimal treatment of uterine serous carcinoma remains unknown, novel therapeutic approaches need to be actively pursued. The molecular targets discussed warrant further investigation and suggest a potential role for therapeutic agents targeting HER-2 and EGFR, as well as downstream targets such as the PI3K-AKT-mTOR pathway in the treatment of uterine serous carcinoma.

Chemotherapy for gynecologic cancers.

This review highlights significant recent developments and trends in chemotherapy for major gynecologic malignancies, i.e., ovarian cancer, endometrial cancer, uterine sarcomas, gestational trophoblastic neoplasia, and cervical cancer. In ovarian cancer, chemotherapeutic options for early, advanced and recurrent disease are in the adjuvant setting as well as in the neoadjuvant setting are explored. For uterine cancer, adjuvant chemotherapy is employed for high risk epithelial subtypes with early disease, such as uterine papillary serous carcinomas, uterine carcinosarcomas and leiomyosarcomas, advanced stage cases, as well as recurrent disease. The review then proceeds to further discuss the appropriate treatment based on the International Federation of Gynecology and Obstetrics prognostic scoring system for gestational trophoblastic neoplasia. Finally, chemotherapy is utilized in cervical cancer as neo-adjuvant therapy prior to surgery or radiation, as a sensitizer concomitantly with radiation therapy or for the treatment of advanced and recurrent disease.

Molecular alterations of EGFR and PIK3CA in uterine serous carcinoma.

OBJECTIVES: Uterine serous carcinoma (USC) is an aggressive endometrial cancer associated with poor prognosis despite comprehensive surgical staging and adjuvant chemotherapy and radiation therapy. Biologic targets have yet to be fully explored in this disease and research on such targets could lead to clinical trials utilizing a new class of therapeutics. This study sought to evaluate primary USC tumors for molecular alterations in epidermal growth factor receptor (EGFR) and the recently characterized oncogene PIK3CA, which encodes the catalytic p110-alpha subunit of phosphatidylinositol 3-kinase (PI3K) and thus activates the AKT-mTOR oncogenic pathway. METHODS: Paraffin-embedded archival tissue of 45 primary USC tumors was utilized in this study. Immunohistochemical analysis of EGFR was performed and cases given a score of 0 to 12 calculated as the product of staining intensity (0 to 3+) and the percentage of positively stained cells (0-4), with 1=1-25%, 2=26-50%, 3=51-75%, and 4=76-100%. For mutational analysis, neoplastic tissue was microdissected and DNA was extracted with phenol-chloroform. Exons 18 through 21 of EGFR and exons 9 and 20 of PIK3CA, the most commonly mutated exons of these genes, were amplified and directly sequenced. RESULTS: When EGFR was evaluated, moderate or strong EGFR membranous staining was observed in 25/45 (56%) USC cases. Thus, a mutational analysis was performed on 35 cases, including all cases with moderate and strong EGFR staining. No mutations were identified in EGFR. In contrast, PIK3CA mutations were confirmed in 5/34 (15%) of USC cases. Four cases were mutated in exon 20 and one case was mutated in exon 9. CONCLUSIONS: Since optimal treatment of uterine serous carcinoma remains unknown, novel therapeutic approaches need to be actively pursued. In the current study of primary USC tumors, oncogenic mutations of the PIK3CA gene were seen in 15% of USC cases. This represents the first report of this gene mutation in USC. In addition, EGFR stained positively in the majority of cases, suggesting a possible target protein. These findings warrant further investigation and suggest a potential role for therapeutic agents targeting the PI3K-AKT-mTOR pathway, such as rapamycin, as well as possible targets of EGFR in the treatment of uterine serous carcinoma.

PIK3CA and PTEN mutations in uterine endometrioid carcinoma and complex atypical hyperplasia.

PURPOSE: The tumor suppressor PTEN gene and the PIK3CA oncogene are frequently mutated in uterine endometrioid carcinoma (UEC). PTEN mutations are also common in complex atypical hyperplasia (CAH), the precursor lesion of UEC. The status of PIK3CA has not yet been explored in CAH. In this study, we evaluated both CAH and UEC for PTEN and PIK3CA mutations. EXPERIMENTAL DESIGN: Neoplastic tissue was microdissected, and DNA was extracted from 29 cases of CAH. DNA was available from 44 UEC cases previously characterized for PTEN mutations. Direct DNA sequencing of exons 9 and 20 of the PIK3CA gene was done on all 73 cases. In addition, CAH cases were analyzed for PTEN mutations. Statistical analyses were done using the Fisher's exact test. RESULTS: Two (7%) of 29 CAH and 17 (39%) of 44 UEC cases contained a PIK3CA mutation (P = 0.003). Fourteen (48%) of 29 CAH cases had a PTEN mutation, but none contained both a PTEN and PIK3CA mutation. Twenty-five (57%) of 44 UEC cases had a PTEN mutation, and 12 (48%) of these 25 cases also contained a PIK3CA mutation. Coexistent PIK3CA and PTEN mutations were significantly correlated with UEC compared with CAH (P = 0.002), but the association in UEC did not reach statistical significance (P = 0.21). CONCLUSIONS: PIK3CA is the most commonly mutated oncogene in UEC; however, mutations are uncommon in CAH. Thus, mutations in PIK3CA, unlike PTEN mutations, are associated with invasion. These findings suggest that mutations in PIK3CA may serve as a marker of invasion with potential clinical use. Furthermore, PIK3CA and PTEN mutations may play distinct roles in endometrial tumorigenesis.