Purpose: An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3). Patients and Methods: Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test. Results: Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas. Conclusion: The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype.

This article reviews recent evidence from the International Agency for Research on Cancer on the best methods of screening for cervical cancer, including by means of conventional cytology, visual inspection with acetic acid, human papillomavirus (HPV) nucleic acid testing, and combinations of these tests. HPV nucleic acid testing was superior whether used alone or in combination with other methods.

The International Anal Neoplasia Society (IANS) developed consensus guidelines to inform anal cancer screening use among various high‐risk groups. Anal cancer incidence estimates by age among risk groups provided the basis to identify risk thresholds to recommend screening. Guided by risk thresholds, screening initiation at age 35 years was recommended for men who have sex with men (MSM) and transgender women (TW) with HIV. For other people with HIV and MSM and TW not with HIV, screening initiation at age 45 years was recommended. For solid organ transplant recipients, screening initiation beginning from 10 years post‐transplant was recommended. For persons with a history of vulvar precancer or cancer, screening initiation was recommended starting within 1 year of diagnosis of vulvar precancer or cancer. Persons aged ≥45 years with a history of cervical/vaginal HSIL or cancer, perianal warts, persistent (>1 year) cervical HPV16, or autoimmune conditions could be considered for screening with shared decision‐making, provided there is adequate capacity to perform diagnostic procedures (high‐resolution anoscopy [HRA]). Anal cytology, high‐risk (hr) human papillomavirus (HPV) testing (including genotyping for HPV16), and hrHPV‐cytology co‐testing are different strategies currently used for anal cancer screening that show acceptable performance. Thresholds for referral for HRA or follow‐up screening tests are delineated. These recommendations from IANS provide the basis to inform management of abnormal screening results, considering currently available screening tools. These guidelines provide a pivotal foundation to help generate consensus among providers and inform the introduction and implementation of risk‐targeted screening for anal cancer prevention.

Significance: Cervical cancer (CxCa) is the second most frequent cancer in women and the third leading cause of cancer death in women worldwide. Our global analysis of gene expression in normal, precancerous, and cancerous cervical tissue shows increased DNA replication/repair and cell proliferation followed by substantial metabolic shifts. We observed a dramatic, progressive decrease in estrogen receptor alpha (ERα) in tumor progression, and ranking specimens by estrogen-responsive gene expression correlated remarkably with histopathology. Whereas ERα expression shuts off in tumor epithelium, stromal fibroblasts in the microenvironment retain ERα, and the data indicate estrogen-related alteration of several candidate stroma–tumor signaling pathways. Our findings strongly support a role of stromal estrogen signaling in CxCa development with implications for CxCa management and control.