ASCCP Committee Opinion: Adjuvant Human Papillomavirus Vaccine for Patients Undergoing Treatment for Cervical Intraepithelial Neoplasia.

OBJECTIVES: Individuals treated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) are at long-term risk of persistent or recurrent disease despite treatment. This committee opinion aims to summarize and provide evidence-based recommendations for adjuvant human papillomavirus (HPV) vaccination based on available, published literature. METHODS: A task force from the ASCCP Practice Committee reviewed current Centers for Disease Control and Prevention (CDC) guidelines and previously published literature about the role of adjuvant HPV vaccination in previously unvaccinated individuals undergoing treatment for CIN2+ and other HPV-related diseases. RESULTS: Current CDC guidelines recommend routine or catch-up HPV vaccination for individuals aged 9 to 26 years, and shared decision making regarding vaccination for individuals aged 27 to 45 years. Multiple published studies suggest a possible benefit for adjuvant HPV vaccination in previously unvaccinated individuals undergoing treatment for CIN2+. CONCLUSIONS: The American Society for Colposcopy and Cervical Pathology recommends adherence to current CDC recommendations for vaccination of individuals aged 9 to 26 years and consideration of the possible benefit of adjuvant HPV vaccination during shared decision making for previously unvaccinated individuals aged 27 to 45 years who are undergoing treatment for CIN2+.

Rethinking Cervical Cancer Screening in Brazil Post COVID-19: A Global Opportunity to Adopt Higher Impact Strategies.

The World Health Organization global call to eliminate cervical cancer encourages countries to consider introducing or improving cervical cancer screening programs. Brazil's Unified Health System (SUS) is among the world's largest public health systems offering free cytology testing, follow-up colposcopy, and treatment. Yet, health care networks across the country have unequal infrastructure, human resources, equipment, and supplies resulting in uneven program performance and large disparities in cervical cancer incidence and mortality. An effective screening program needs multiple strategies feasible for each community's reality, facilitating coverage and follow-up adherence. Prioritizing those at highest risk with tests that better stratify risk will limit inefficiencies, improving program impact across different resource settings. Highly sensitive human papillomavirus (HPV)-DNA testing performs better than cytology and, with self-collection closer to homes and workplaces, improves access, even in remote regions. Molecular triage strategies like HPV genotyping can identify from the same self-collected sample, those at highest risk requiring follow-up. If proven acceptable, affordable, cost-effective, and efficient in the Brazilian context, these strategies would increase coverage while removing the need for speculum exams for routine screening and reducing follow-up visits. SUS could implement a nationwide organized program that accommodates heterogenous settings across Brazil, informing a variety of screening programs worldwide.

The ASCCP Cervical Cancer Screening Task Force Endorsement and Opinion on the American Cancer Society Updated Cervical Cancer Screening Guidelines.

ABSTRACT: The American Cancer Society (ACS) released updated cervical cancer screening guidelines in 2020 that endorse a shift in practice to primary human papillomavirus (HPV) screening in people with a cervix, beginning at ages of 25-65 years. When access to US Food and Drug Administration-approved primary HPV testing is not available, the ACS offers cotesting or cytology as acceptable alternative strategies but suggests that these testing modalities may be excluded from future iterations of the guidelines. The ASCCP recognizes the benefits and risks of primary HPV cervical cancer screening while acknowledging the barriers to widespread adoption, including implementation issues, the impact of limited HPV vaccination in the United States, and inclusion of populations who may not be well represented on primary HPV screening trials, such as underrepresented minorities. The ASCCP endorses the 2018 US Preventive Services Task Force Recommendation Statement and supports the ACS cervical cancer screening guidelines. Most importantly, the ASCCP endorses any cervical cancer screening for secondary prevention of cervical cancer and recommends interventions that improve screening for those who are underscreened or unscreened.

A Pilot Study of Human Papillomavirus Detection in Urine Using a Novel Nucleic Acid Amplification Test.

INTRODUCTION: Human papillomavirus (HPV) testing is the standard-of-care for cervical cancer screening globally. Urine is a promising alternative to collecting a cervical specimen during a pelvic exam for HPV testing. There are no studies to date of HPV testing of urine using the Xpert HPV test. METHODS: We conducted a pilot study of 40 women; 30 women undergoing colposcopy because of a previous abnormality and 10 undergoing routine screening, to evaluate HPV detection in urine by the Xpert HPV test on the GeneXpert platform. Xpert HPV testing of urine was done according to the manufacturer's instructions for testing cervical specimens. These results were compared to a reference of combined results of 2 research HPV genotyping tests conducted on cervical specimens and to repeat Xpert HPV testing of urine. RESULTS: Analytic sensitivity and specificity of Xpert testing of urine for any high-risk HPV versus the cervical sample, categorized as HPV positive if at least 1 test was positive, were 64.3% (95% confidence interval [95%CI] = 42.1-76.1%) and 100% (97.5%CI = 71.5-100%), respectively. Analytic sensitivity and specificity of Xpert testing of urine for any high-risk HPV versus the cervical sample, categorized as positive if both tests were positive, were 66.7% (95%CI = 44.7-84.4%) and 86.7% (95%CI = 59.5-98.3%), respectively. Kappa values for first vs. second and first vs. third testing of urine by Xpert were 0.89 (95%CI = 0.79-1.00) and 0.90 (95%CI = 0.81-1.00), respectively. DISCUSSION: Given the call for global elimination of cervical cancer and widespread availability of GeneXpert, optimizing Xpert HPV testing of urine may be warranted.

Direct oral anticoagulant use in gynecologic oncology: A Society of Gynecologic Oncology Clinical Practice Statement.

Venous thromboembolism (VTE) is a common cause of morbidity and mortality in women with gynecologic malignancies. This practice statement provides clinical data and overall quality of evidence regarding the use of direct oral anticoagulants (DOACs) in this patient population. Specifically, it reviews patient selection, safety measures, and nuances of perioperative use of these medications. The scope of this document is limited to DOAC use in gynecologic oncology rather than a broad discussion of VTE prophylaxis and management in general. The following recommendations and examination of extant data are based on DOAC trials conducted primarily in mixed populations with different cancer subtypes. Many of these trials include few, or no, women with gynecologic cancer. However, because there is very limited data in gynecologic cancer-specific populations, the results of these studies represent the best available evidence to support treatment recommendations in our patients. The members of the Society of Gynecologic Oncology (SGO) Clinical Practice Committee believe that the results of these studies may be extrapolated, with caution, to VTE treatment and prophylaxis for patients with gynecologic cancer.

A demonstration of automated visual evaluation of cervical images taken with a smartphone camera.

We examined whether automated visual evaluation (AVE), a deep learning computer application for cervical cancer screening, can be used on cervix images taken by a contemporary smartphone camera. A large number of cervix images acquired by the commercial MobileODT EVA system were filtered for acceptable visual quality and then 7587 filtered images from 3221 women were annotated by a group of gynecologic oncologists (so the gold standard is an expert impression, not histopathology). We tested and analyzed on multiple random splits of the images using two deep learning, object detection networks. For all the receiver operating characteristics curves, the area under the curve values for the discrimination of the most likely precancer cases from least likely cases (most likely controls) were above 0.90. These results showed that AVE can classify cervix images with confidence scores that are strongly associated with expert evaluations of severity for the same images. The results on a small subset of images that have histopathologic diagnoses further supported the capability of AVE for predicting cervical precancer. We examined the associations of AVE severity score with gynecologic oncologist impression at all regions where we had a sufficient number of cases and controls, and the influence of a woman's age. The method was found generally resilient to regional variation in the appearance of the cervix. This work suggests that using AVE on smartphones could be a useful adjunct to health-worker visual assessment with acetic acid, a cervical cancer screening method commonly used in low- and middle-resource settings.

Severe hypertriglyceridemia during treatment with intraperitoneal cisplatin and paclitaxel for advanced stage fallopian tube carcinoma.

This case report describes a patient who developed severe hypertriglyceridemia (1871 mg/dL) and hyperlipidemia (LDL 132 mg/dL) during intraperitoneal (IP) administration of cisplatin and paclitaxel as adjuvant treatment for stage IIIC fallopian tube carcinoma. After an evaluation with her primary care physician, she was treated with gemfibrozil and rosuvastatin for the duration of her treatment. There was complete resolution of hypertriglyceridemia after completion of chemotherapy. This adverse event is rare and has not been reported in the literature with this chemotherapeutic regimen. A pre-chemotherapy evaluation for dyslipidemia may be beneficial in the detection and monitoring of this condition.

A Deceptive Spread: Myoinvasion of Endometrial Carcinoma Imitating Adenoma Malignum.

Endometrioid type of endometrial carcinoma is the most common form of uterine malignancy. The majority of patients in the developed world present with the low-grade, low-stage type of this malignancy. The current treatment of early-stage endometrioid carcinoma provides most patients with a favorable outcome. One of the important factors that determine the outcome of early-stage endometrial carcinoma is the involvement of cervical stroma. One of the very rare forms of cervical stromal involvement by endometrioid carcinoma is termed "adenoma malignum type" invasion due to its similarity to the infamously deceptive type of cervical adenocarcinoma called adenoma malignum. Since adenoma malignum is often discovered incidentally, finding adenoma malignum type of myoinvasion may deceive a pathologist to diagnose the simultaneous presence of endometrial carcinoma and adenoma malignum in the same patient as 2 separate entities. Also, this type of myoinvasion may be missed altogether for its subtle nature. In this article, we report a case of low-grade, low-stage endometrioid carcinoma with adenoma malignum type of myoinvasion. We have pointed out the subtle nature of this lesion and the important features to remember to successfully identify it.

Recurrence, death, and secondary malignancy after ovarian conservation for young women with early-stage low-grade endometrial cancer.

OBJECTIVE: To examine the association between ovarian conservation and oncologic outcome in surgically-treated young women with early-stage, low-grade endometrial cancer. METHODS: This multicenter retrospective study examined women aged <50 with stage I grade 1-2 endometrioid endometrial cancer who underwent primary surgery with hysterectomy from 2000 to 2014 (US cohort n = 1196, and Japan cohort n = 495). Recurrence patterns, survival, and the presence of a metachronous secondary malignancy were assessed based on ovarian conservation versus oophorectomy. RESULTS: During the study period, the ovarian conservation rate significantly increased in the US cohort from 5.4% to 16.4% (P = 0.020) whereas the rate was unchanged in the Japan cohort (6.3-8.7%, P = 0.787). In the US cohort, ovarian conservation was not associated with disease-free survival (hazard ratio [HR] 0.829, 95% confidence interval [CI] 0.188-3.663, P = 0.805), overall survival (HR not estimated, P = 0.981), or metachronous secondary malignancy (HR 1.787, 95% CI 0.603-5.295, P = 0.295). In the Japan cohort, ovarian conservation was associated with decreased disease-free survival (HR 5.214, 95% CI 1.557-17.464, P = 0.007) and an increased risk of a metachronous secondary malignancy, particularly ovarian cancer (HR 7.119, 95% CI 1.349-37.554, P = 0.021), but was not associated with overall survival (HR not estimated, P = 0.987). Ovarian recurrence or metachronous secondary ovarian cancer occurred after a median time of 5.9 years, and all cases were salvaged. CONCLUSION: Our study suggests that adoption of ovarian conservation in young women with early-stage low-grade endometrial cancer varies by population. Ovarian conservation for young women with early-stage, low-grade endometrial cancer may be potentially associated with increased risks of ovarian recurrence or metachronous secondary ovarian cancer in certain populations; nevertheless, ovarian conservation did not negatively impact overall survival.

Pitfalls of Frozen Section in Gynecological Pathology: A Rare Case of Ovarian Lymphoma in an HIV-Positive Woman Resembling Dysgerminoma on Frozen Section.

Primary lymphoma of the ovary, particularly in an HIV-positive woman, is exceptionally rare, and ovarian lymphoma may not be considered at the time of intraoperative consultation. In this article, we present a case in an HIV-positive woman thought to be a dysgerminoma at the time of frozen section, but which was found to be a diffuse large B-cell lymphoma of the ovary.

Female Sex Hormone Receptor Profiling in Uterine Adenosarcomas.

OBJECTIVE: This study aimed to identify the hormonal receptor status in uterine adenosarcoma (AS) and uterine AS with sarcomatous overgrowth (AS + SO), including those with high-grade histologic features (nuclear pleomorphism, atypical mitoses, necrosis), with or without heterologous elements. Estrogen receptor (ER) status, including estrogen receptor α (ERα), estrogen receptor ß (ERß), and G protein-coupled estrogen receptor (GPER), and progesterone receptor (PgR) status were examined. METHODS: From August 2001 to November 2013, 11 patients with histologic diagnosis of uterine AS were identified. Tumor tissue sections were stained for ERα, ERß, GPER, and PgR and examined both for percentage of overall cells stained and for intensity of staining. Descriptive statistics were calculated using clinicopathologic data abstracted from the medical record. RESULTS: Eight cases of AS and 3 cases of AS with high-grade features were identified. Seven of 8 tumor samples of AS showed strong or moderate intensity immunostaining for ERα; all AS + SO tumor samples showed minimal to no immunoreactivity for ERα. There was a significant decrease in ERα H scores in high-grade tumors when compared with AS (P = 0.01). Lower PgR H scores were observed in high-grade tumors compared with those in AS (P = 0.04). Estrogen receptor ß immunostaining was variable, and GPER immunostaining was absent in the majority of tumor samples. CONCLUSIONS: Higher expression of ERα and PgR was observed in AS when compared with those with AS + SO and high-grade features. Both tumor subtypes showed similar levels of ERß and GPER expression, although significant differences in ERß and GPER expression were not detected. In contrast to our previous findings in uterine carcinosarcoma, ERs ERß and GPER do not seem to play a significant role in AS in this study.

Impact of lympho-vascular space invasion on tumor characteristics and survival outcome of women with low-grade serous ovarian carcinoma.

BACKGROUND AND OBJECTIVES: To examine association of lympho-vascular space invasion (LVSI) with clinico-pathological factors and to evaluate survival of women with low-grade serous ovarian carcinoma containing areas of LVSI. METHODS: This is a multicenter retrospective study examining consecutive cases of surgically treated stage I-IV low-grade serous ovarian carcinoma (n = 178). Archived histopathology slides for the ovarian tumors were reviewed, and LVSI was scored as present or absent. LVSI status was correlated to clinico-pathological findings and survival outcome. RESULTS: LVSI was seen in 79 cases (44.4%, 95% confidence interval [CI] 37.1-51.7). LVSI was associated with increased risk of omental metastasis (87.0% vs 64.9%, odds ratio [OR] 3.62, P = 0.001), high pelvic lymph node ratio (median 12.9% vs 0%, P = 0.012), and malignant ascites (49.3% vs 32.6%, OR 2.01, P = 0.035). On multivariable analysis, controlling for age, stage, and cytoreductive status, presence of LVSI in the ovarian tumor remained an independent predictor for decreased progression-free survival (5-year rates 21.0% vs 35.7%, adjusted-hazard ratio 1.57, 95%CI 1.06-2.34, P = 0.026). LVSI was significantly associated with increased risk of recurrence in lymph nodes (OR 2.62, 95%CI 1.08-6.35, P = 0.047). CONCLUSION: LVSI in the ovarian tumor is associated with adverse clinico-pathological characteristics and decreased progression-free survival in women with low-grade serous ovarian carcinoma.

Prognosis of women with stage I endometrioid endometrial cancer and synchronous stage I endometrioid ovarian cancer.

OBJECTIVE: Synchronous endometrial and ovarian cancer with endometrioid histology at two cancer sites typically presents with early-stage disease and is thought to have a good prognosis. We examined the survival of women with early-stage endometrioid endometrial cancer who had synchronous early-stage endometrioid ovarian cancer. METHODS: This is a retrospective case-control study examining the Surveillance, Epidemiology, and End Result Program between 1973 and 2013. Survival of women with stage I endometrioid endometrial cancer with stage I endometrioid ovarian cancer (n=839) were compared to women with stage I endometrioid endometrial cancer without synchronous ovarian cancer (n=123,692) after propensity score matching. RESULTS: Women with synchronous stage I endometrioid ovarian cancer were more likely to be diagnosed recently, be younger, have stage IA disease, grade 1 tumors, to have undergone lymphadenectomy, and were less likely to receive radiotherapy compared to those without synchronous ovarian cancer (all, P<0.001). In a propensity score matched model, the presence of synchronous ovarian cancer was not associated with endometrial cancer-specific survival (10-year rates 96.0% versus 95.3%, P=0.97) or overall survival (85.6% versus 87.2%, P=0.10). Among tumors with concordant grades at the two cancer sites, survival was similar regardless of presence of synchronous ovarian tumors (grade 1 tumors, 10-year rate for overall survival, 88.2% versus 89.1%, P=0.40; and grade 2 tumors, 84.0% versus 85.8%, P=0.78). CONCLUSION: Women with stage I endometrioid endometrial cancer with synchronous stage I endometrioid ovarian cancer have a survival outcome similar to those with stage I endometrioid endometrial cancer without synchronous ovarian cancer.

Virilization and Enlarged Ovaries in a Postmenopausal Woman.

A patient with postmenopausal bleeding and virilization was found to have bilaterally enlarged ovaries with a yellow cut surface. Histology revealed cortical stromal hyperplasia with stromal hyperthecosis. This hyperplastic condition should not be mistaken for an ovarian neoplasm.