2019 ASCCP Risk-Based Management Consensus Guidelines: Updates Through 2023.

ABSTRACT: This Research Letter summarizes all updates to the 2019 Guidelines through September 2023, including: endorsement of the 2021 Opportunistic Infections guidelines for HIV+ or immunosuppressed patients; clarification of use of human papillomavirus testing alone for patients undergoing observation for cervical intraepithelial neoplasia 2; revision of unsatisfactory cytology management; clarification that 2012 guidelines should be followed for patients aged 25 years and older screened with cytology only; management of patients for whom colposcopy was recommended but not completed; clarification that after treatment for cervical intraepithelial neoplasia 2+, 3 negative human papillomavirus tests or cotests at 6, 18, and 30 months are recommended before the patient can return to a 3-year testing interval; and clarification of postcolposcopy management of minimally abnormal results.

American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer.

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from six working groups, and a recent symposium co-sponsored by the ACS, American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP), which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (e.g., management of screen positives and screening interval for screen negatives) of women after screening, age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16/18 infections.

Factors that influence the rate of epithelial maturation in the cervix in healthy young women.

PURPOSE: To examine the longitudinal changes in the epithelial topography of the cervix in healthy young women; and to determine the sociodemographic, behavioral, and biological factors associated with the rate of cervical epithelial maturation. METHODS: Healthy young women were enrolled from October 2000 to September 2002 as part of a larger study of human papillomavirus (HPV). At interval visits, interviews, infection testing, and colpophotography (3% acetic acid; 10x, 16x magnifications) were performed. Areas of total cervical face and cervical immaturity, defined as columnar and early squamous metaplasia, were quantitatively measured using computerized planimetry. Cervical immaturity was expressed as percentage of total cervical face. This analysis includes the first consecutive 145 women with greater than 10% immaturity at baseline. The rate of cervical maturation was defined as change in percent-immaturity. Predictors included sociodemographics, sexual behaviors, and infections. Data analyses included multivariate generalized linear models with repeated measures. RESULTS: The baseline mean age was 17.8 years. Colpophotographs were available from 815 total visits, representing 2.7 years mean follow-up per woman and 5.9-month mean intervals. Women began the study with a median of 39% immaturity and ended with 8% immaturity. After adjusting for time and baseline percent-immaturity, an increased rate of cervical maturation was associated with oral contraceptive pill use (parameter estimate -.023, p =.04) and smoking (-.039, p =.01). CONCLUSIONS: Cervical maturation was documented during relatively short time periods for the vast majority of these women. Oral contraceptive pills and smoking may accelerate the maturational process, representing increased cell proliferation and thus a possible greater vulnerability to HPV.

HPV Vaccines: today and in the Future.

Human papillomavirus (HPV) is responsible for 99.7% of cervical cancer cases and an estimated 5% of all cancers worldwide. The largest burden from HPV-associated cervical cancers is in developing nations where effective cervical cancer screening programs are nonexistent. Even in developed nations, diagnosis and treatment of cervical precancers continue to be large economic burdens. Prophylactic vaccination against HPV is an ideal method for the prevention of cervical cancer and other HPV associated diseases. Safe and effective virus-like-particle-derived prophylactic vaccines are available to most nations. The high cost of the current vaccines makes it out of reach for most developing nations. Because millions of women are already infected with HPV and have serious disease, therapeutic HPV vaccines are being developed to treat these women. This article presents the natural history, oncogenesis, and host immune interactions of HPV and associated diseases. The article also discusses the safety and efficacy of commercially available prophylactic vaccines against HPV, as well as novel prophylactic and therapeutic vaccine delivery strategies in early clinical development.

Determination of cytokine protein levels in cervical mucus samples from young women by a multiplex immunoassay method and assessment of correlates.

Cytokines in cervical mucus are likely to play important roles in controlling pathogens. The cervical mucosal environment is complex, however, with many endogenous and exogenous factors that may affect cytokine levels. We used a multiplex, suspension-array-based immunoassay method to measure 10 proinflammatory (interleukin-1beta [IL-1beta], IL-6, and IL-8) and immunoregulatory (gamma interferon [IFN-gamma], IL-2, IL-4, IL-5, IL-10, IL-12, and IL-13) cytokines in cervical mucus specimens collected via ophthalmic sponge from 72 healthy, nonpregnant women and correlate their levels with biologic and behavioral covariates in a cross-sectional design. Proinflammatory and immunoregulatory cytokines were readily detected, although proinflammatory cytokines were present at markedly higher levels than were immunoregulatory cytokines. Among the covariates examined, the most striking finding was the significant (P < or = 0.05) association between depressed levels of the cytokines IFN-gamma, IL-1beta, IL-6, and IL-10 and cigarette smoking. Also, nonsignificant trends toward lower cytokine levels were found in the settings of incident and persistent human papillomavirus infection. The ready detection of proinflammatory cytokines may be reflective of the female genital tract as an anatomic site that is constantly exposed to immunogenic stimulation. Cigarette smoking appears to downregulate cytokine responses in the cervical mucosa, which may help explain the implicated role of tobacco use as a cofactor for cervical cancer development.

Utility of cervicography in HIV-infected and uninfected adolescents.

PURPOSE: To compare cytology with cervicography in HIV-infected and uninfected adolescent females. METHODS: At the time of analysis, 334 girls aged 13-19 years from 13 U.S. cities were participating in a prospective study of HIV infection. All subjects had cytology and a Cervigram (cervicography) performed at two consecutive visits 6 months apart, referred to as visit (V) 1 and 2. Cervigrams were sent to the parent company for diagnosis and were categorized as: "negative" or "positive" (compatible with low-grade or high-grade squamous intraepithelial lesions [SIL]). Cytology was considered abnormal if the subject had SIL at either V1 or V2. Sensitivity, specificity, and positive predictive value (PPV) of the Cervigram were calculated compared with repeat Papanicolaou (Pap) smears. RESULTS: Two consecutive adequate Pap smears were available for analysis in 200 adolescents; 51% (95% CI, 43-59) of the 142 HIV-positive youth and 19% (95% CI, 9-29) of the 58 HIV-negative youth had SIL on at least one Pap smear (p < .001). A positive Cervigram was observed in 44% (95% CI, 36-53) of the HIV-infected group and 29% (95% CI, 17-41) of the HIV-uninfected group (p =.06). For the HIV-infected group, the sensitivity, specificity, and PPV of the Cervigram to detect SIL were 58% (95% CI, 45-71), 69% (95%CI, 57-80), and 64% (95%CI, 52-77), respectively. For the HIV-uninfected group, the sensitivity, specificity, and PPV were 64% (95% CI, 31-89), 80% (95% CI, 65-90), and 44% (95% CI, 19-68), respectively. The combined sensitivity, using both the Pap smear and Cervigram result from V1 to detect SIL, was 82% (95% CI, 71-91 for HIV+ and 48-98 for HIV-) in both groups. However, the PPV based the performance of the Cervigram in Pap smear-negative women as 33% (95% CI, 17-53) and 15% (95% CI, 2-45) for the HIV-infected and uninfected group, respectively (p = not significant [ns]). CONCLUSIONS: Although the sensitivity of a single Pap smear increased significantly when the Cervigram was used as an adjunct, the low PPV in both HIV-infected and uninfected groups, suggests that cervicography has a limited utility for precancer and cervical cancer screening in high-risk adolescent populations.