Changing paradigms in the systemic treatment of advanced cervical cancer.

Despite availability of primary and secondary prevention measures, cervical cancer persists as one of the most common cancers among women around the world. Although early-stage disease can be cured with radical and even fertility-sparing surgery, patients with metastatic and recurrent cervical cancer have poor prognosis with historically limited treatment options and incurable disease. Significant advances in cervical cancer treatment have emerged as the result of clinical trials that have sought to determine the best therapy to prolong overall and progression-free survival. Most recently, trials that have involved angiogenesis blockade in addition to standard chemotherapy have demonstrated improved overall and progression-free survival. This review serves to highlight pivotal trials in chemotherapy development for advanced, metastatic, and recurrent cervical cancer that includes the paradigm-shifting work that demonstrates increased overall survival with angiogenesis blockade.

A critical assessment of morcellation and its impact on gynecologic surgery and the limitations of the existing literature.

Uterine sarcomas are rare uterine malignancies that are difficult to diagnose preoperatively. Because of cases of disseminated sarcoma after laparoscopic hysterectomy, the role of power morcellators in gynecologic surgery has been questioned. Morcellation is an integral part of making laparoscopic surgery possible for the removal of large uterine leiomyomata, and the development of power morcellation has increased efficiency during these procedures. Minimally invasive surgery has demonstrated benefits that include improved pain control, decreased infection risk, and faster surgical recovery and return to work. In this review, we examine the risk of incidental sarcoma at the time of surgery, the quality of the data, the accuracy of clinical and radiologic predictors of uterine sarcoma, and the impact of morcellation on the prognosis of uterine sarcoma.

The Effect of Cryotherapy on Human Papillomavirus Clearance Among HIV-Positive Women in Lusaka, Zambia.

OBJECTIVE: We sought to investigate the progression of human papillomaviruses (HPV) infection in HIV-positive women after cryotherapy. METHODS: We examined changes in detection of high-risk HPV (hrHPV) cervical infections among HIV-infected women over a 12-week period after cryotherapy using stored specimens from a cohort study conducted between June 2009 and March 2011 in Lusaka, Zambia. Samples from visits at baseline and weeks 4, 8, and 12 were tested using the Roche Linear Array assay. RESULTS: A total of 89 women were included in the analysis. The median age was 32 years (interquartile range [IQR], 28-36 years). The median CD4+ cell count was 350 cells/µL (IQR, 214-470 cells/µL), and 66% of women were receiving antiretroviral therapy. At baseline, the prevalence of hrHPV was 91% (95% confidence interval [CI], 83%-95%). HPV45 was the most common HPV type, present in (30%) women, followed by HPV16 (27%), HPV18 (27%), HPV51 (20%), and HPV58 (22%). Among women with valid results both at baseline and 12 weeks, 25% (17/67) cleared their initial hrHPV infection within 12 weeks of treatment, although 65% (11/17) had new hrHPV types detected. CONCLUSIONS: Cryotherapy led to clearance of 25% of hrHPV infections within 12 weeks of treatment. However, hrHPV infection remained persistent in most women, and new hrHPV types were detected often, explaining the high rate of persistence and recurrence of cervical disease in this population. Continued efforts to scale up HPV vaccination and cervical screening should remain a priority in high HIV burden settings such as Zambia.

Gynaecologic oncology surgical cancellations in Zambia.

Introduction: Cancellations of elective surgery in low-and middle-income countries (LMIC) are common and a major hindrance for patients who are in need of surgical therapeutic modalities. This is especially important in the context of scaling up needed surgical interventions for gynaecological cancer care. There is a knowledge gap in the literature related to cancellation of gynaecologic oncology surgeries in LMIC, where there is enormous need for this specific cancer surgical capacity. We report in an observational descriptive fashion, our experience at the UTH/CDH in Lusaka, Zambia, on the causes of surgical cancellations in gynaecologic oncology. Methods: From January 1, 2021 through June 31, 2023, we retrospectively evaluated the surgical registry for gynaecologic oncology at the UTH/CDH in Lusaka, Zambia to assess the number and causes of surgical cancellations. Results: There were a total of 66 (16.96%) surgical cancellations out of 389 scheduled gynaecologic oncology cases. Lack of available blood and/or low haemoglobin was the most frequent cause of surgical cancellations, 27 cases (40.90%). Conclusion: We highlight in our series that the lack of blood, leading to surgical cancellations was the most frequent impediment related to performing scheduled gynaecologic oncology surgical procedures. As gynaecologic oncology services scale up in LMIC, given the radical nature of surgery and its association with blood loss, it is incumbent on the entire clinical ecosystem to address this issue and to develop mitigating strategies, specific to their respective resource setting.

Breast, Ovarian, Uterine, Vaginal, and Vulvar Cancer Care in Low- and Middle-Income Countries: Prevalence, Screening, Treatment, Palliative Care, and Human Resources Training.

Breast, ovarian, uterine, vaginal, and vulvar cancers pose a significant risk to women's lives in low- and middle-income countries due to increasing incidence and presentation with advanced stage disease. There are challenges to screening and early detection and limitations in access to treatment and palliative care, and the current global health care workforce is insufficient. However, there is promise in development of telehealth strategies, task shifting, and increasing number of physician training programs to help address currently unmet needs.

Comparison of a U.S. and Zambian Ob/Gyn Residency Training Programme.

Introduction: The major objective of the study was to compare and contrast a U.S. and Zambian Ob/Gyn residency programme, using uniform metrics, as the basis for an initial exploration of perceived inequities in post-graduate medical education between low- and high-income countries. Methods: Measurements of the following procedures were used to indicate whether minimum standards had been met by trainees in their respective postgraduate programmes: vaginal deliveries; C-sections; abdominal, vaginal and laparoscopic hysterectomies; other laparoscopic surgeries; cancer cases; abortions; obstetrical ultrasounds; cystoscopies; incontinence and pelvic floor surgeries. Evaluations were also made with respect to the presence or absence of an official ultrasound rotation, subspeciality and off-service rotations, protected didactic time and exclusive time on obstetrics and gynaecologic clinical services. Comparisons were made relative to these various categories and the average procedural numbers at each level of training to determine differences in trends and degree of exposure. Results: Minimal procedural requirements were met by both the U.S. and Zambian programmes. For open surgical cases, the minimum standards were higher for the Zambian programme, whereas for procedures associated with the use of high-end technology, such as ultrasound and minimally invasive surgery, minimum standards were higher for the U.S. programme. Conclusion: There were no significant differences in the Zambian and U.S. Ob/Gyn post-graduate training programmes, relative to their respective metrics. A more extensive analysis is required to determine the actual competency levels that are produced by the respective training systems.

Advancing cervical cancer prevention initiatives in resource-constrained settings: insights from the Cervical Cancer Prevention Program in Zambia.

Groesbeck Parham and colleagues describe their Cervical Cancer Prevention Program in Zambia, which has provided services to over 58,000 women over the past five years, and share lessons learned from the program's implementation and integration with existing HIV/AIDS programs.

eC3--a modern telecommunications matrix for cervical cancer prevention in Zambia.

OBJECTIVES: Low physician density, undercapacitated laboratory infrastructures, and limited resources are major limitations to the development and implementation of widely accessible cervical cancer prevention programs in sub-Saharan Africa. MATERIALS AND METHODS: We developed a system operated by nonphysician health providers that used widely available and affordable communication technology to create locally adaptable and sustainable public sector cervical cancer prevention program in Zambia, one of the world's poorest countries. RESULTS: Nurses were trained to perform visual inspection with acetic acid aided by digital cervicography using predefined criteria. Electronic digital images (cervigrams) were reviewed with patients, and distance consultation was sought as necessary. Same-visit cryotherapy or referral for further evaluation by a gynecologist was offered. The Zambian system of "electronic cervical cancer control" bypasses many of the historic barriers to the delivery of preventive health care to women in low-resource environments while facilitating monitoring, evaluation, and continued education of primary health care providers, patient education, and medical records documentation. CONCLUSIONS: The electronic cervical cancer control system uses appropriate technology to bridge the gap between screening and diagnosis, thereby facilitating the conduct of "screen-and-treat" programs. The inherent flexibility of the system lends itself to the integration with future infrastructures using rapid molecular human papillomavirus-based screening approaches and wireless telemedicine communications.

Rapid progression of disease in two cases of undifferentiated endometrial carcinoma.

Undifferentiated endometrial carcinoma, a rare histopathologic diagnosis, has a poor prognosis with high risk of progression during or shortly after completion of adjuvant treatment. We present two cases of undifferentiated endometrial carcinoma: one in a postmenopausal female who experienced recurrent disease immediately after completion of adjuvant treatment and one in a premenopausal female who experienced disease progression while receiving adjuvant treatment. These cases exemplify the aggressive behavior of undifferentiated endometrial carcinoma and suggest the need for a more effective treatment in the upfront setting than the current standard of care for endometrioid endometrial adenocarcinoma.

Management of cryotherapy-ineligible women in a "screen-and-treat" cervical cancer prevention program targeting HIV-infected women in Zambia: lessons from the field.

OBJECTIVE: We demonstrate the feasibility of implementing a referral and management system for cryotherapy-ineligible women in a "screen-and-treat" cervical cancer prevention program targeting HIV-infected women in Zambia. METHODS: We established criteria for patient referral, developed a training program for loop electrosurgical excision procedure (LEEP) providers, and adapted LEEP to a resource-constrained setting. RESULTS: We successfully trained 15 nurses to perform visual inspection with acetic acid (VIA) followed by immediate cryotherapy. Women with positive tests but ineligible for cryotherapy were referred for further evaluation. We trained four Zambian physicians to evaluate referrals, perform punch biopsy, LEEP, and manage intra-operative and post-operative complications. From January 2006 through October 2007, a total of 8823 women (41.5% HIV seropositive) were evaluated by nurses in outlying prevention clinics; of these, 1477 (16.7%) were referred for physician evaluation based on established criteria. Of the 875 (59.2% of 1147 referred) that presented for evaluation, 748 (8.4% of total screened) underwent histologic evaluation in the form of punch biopsy or LEEP. Complications associated with LEEP included anesthesia reaction (n=2) which spontaneously resolved, intra-operative (n=12) and post-operative (n=2) bleeding managed by local measures, and post-operative infection (n=12) managed with antibiotics. CONCLUSION: With adaptations for a resource-constrained environment, we have demonstrated that performing LEEP is feasible and safe, with low rates of complications that can be managed locally. It is important to establish referral and management systems using LEEP-based excisional evaluation for women with cryotherapy-ineligible lesions in VIA-based "screen-and-treat" protocols nested within HIV-care programs in resource-constrained settings.

Bevacizumab in Cervical Cancer: 5 Years After.

Over the past 5 years, addition of bevacizumab to combination chemotherapy for advanced, recurrent, and persistent cervical cancer has offered prolonged overall and progression-free survival. Since the original press release announcing the survival benefits of this antiangiogenesis therapy, there has been further study of bevacizumab related to quality of life, combination with other agents, use of imaging to evaluate likelihood of response, and development of biosimilars. This review summarizes publications related to bevacizumab use in advanced, recurrent, and persistent cervical cancer over the past 5 years since initial proof of concept of antiangiogenesis therapy and the initial dissemination of information regarding survival benefits of bevacizumab.

Disparities in Adherence to National Comprehensive Cancer Network Treatment Guidelines and Survival for Stage IB-IIA Cervical Cancer in California.

OBJECTIVE: To evaluate the association of sociodemographic and hospital characteristics with adherence to National Comprehensive Cancer Network treatment guidelines for stage IB-IIA cervical cancer and to analyze the relationship between adherent care and survival. METHODS: This is a retrospective population-based cohort study of patients with stage IB-IIA invasive cervical cancer reported to the California Cancer Registry from January 1, 1995, through December 31, 2009. Adherence to National Comprehensive Cancer Network guideline care was defined by year- and stage-appropriate surgical procedures, radiation, and chemotherapy. Multivariate logistic regression, Kaplan-Meier estimate, and Cox proportional hazard models were used to examine associations between patient, tumor, and treatment characteristics and National Comprehensive Cancer Network guideline adherence and cervical cancer-specific 5-year survival. RESULTS: A total of 6,063 patients were identified. Forty-seven percent received National Comprehensive Cancer Network guideline-adherent care, and 18.8% were treated in high-volume centers (20 or more patients/year). On multivariate analysis, lowest socioeconomic status (adjusted odds ratio [OR] 0.69, 95% CI 0.57-0.84), low-middle socioeconomic status (adjusted OR 0.76, 95% CI 0.64-0.92), and Charlson-Deyo comorbidity score 1 or higher (adjusted OR 0.78, 95% CI 0.69-0.89) were patient characteristics associated with receipt of nonguideline care. Receiving adherent care was less common in low-volume centers (45.9%) than in high-volume centers (50.9%) (effect size 0.90, 95% CI 0.84-0.96). Death from cervical cancer was more common in the nonadherent group (13.3%) than in the adherent group (8.6%) (effect size 1.55, 95% CI 1.34-1.80). Black race (adjusted hazard ratio 1.56, 95% CI 1.08-2.27), Medicaid payer status (adjusted hazard ratio 1.47, 95% CI 1.15-1.87), and Charlson-Deyo comorbidity score 1 or higher (adjusted hazard ratio 2.07, 95% CI 1.68-2.56) were all associated with increased risk of dying from cervical cancer. CONCLUSION: Among patients with early-stage cervical cancer, National Comprehensive Cancer Network guideline-nonadherent care was independently associated with increased cervical cancer-specific mortality along with black race and Medicaid payer status. Nonadherence was more prevalent in patients with older age, lower socioeconomic status, and receipt of care in low-volume centers. Attention should be paid to increase guideline adherence.

Cervical cancer survivorship: long-term quality of life and social support.

PURPOSE: Surgery, radiotherapy, and chemotherapy are the mainstays of cervical cancer treatment. Many patients receive multiple treatment modalities, each with its own long-term effects. Given the high 5-year survival rate for cervical cancer patients, evaluation and improvement of long-term quality of life are essential. METHODS: Pertinent articles were identified through searches of PubMed for literature published from 1993 to 2014. We summarize quality of life data from long-term follow-up studies of cervical cancer patients. We additionally summarize small group interviews of Hispanic and non-Hispanic cervical cancer survivors regarding social support and coping. FINDINGS: Data are varied in terms of the long-term impact of treatment on quality of life, but consistent in suggesting that patients who receive radiotherapy as part of their treatment have the highest risk of increased long-term dysfunction of bladder and bowel, as well as sexual dysfunction and psychosocial consequences. Rigorous investigations regarding long-term consequences of treatment modalities are lacking. IMPLICATIONS: Continued work to improve treatment outcomes and survival should also include a focus on reducing adverse long-term side effects. Providing supportive care during treatment and evaluating the effects of supportive care can reduce the prevalence and magnitude of long-term sequelae of cervical cancer, which will in turn improve quality of life and quality of care.

Implementation and Operational Research: Age Distribution and Determinants of Invasive Cervical Cancer in a "Screen-and-Treat" Program Integrated With HIV/AIDS Care in Zambia.

BACKGROUND: Cervical cancer screening efforts linked to HIV/AIDS care programs are being expanded across sub-Saharan Africa. Evidence on the age distribution and determinants of invasive cervical cancer (ICC) cases detected in such programs is limited. METHODS: We analyzed program operations data from the Cervical Cancer Prevention Program in Zambia, the largest public sector programs of its kind in sub-Saharan Africa. We examined age distribution patterns by HIV serostatus of histologically confirmed ICC cases and used multivariable logistic regression to evaluate independent risk factors for ICC among younger (≤35 years) and older (>35 years) women. RESULTS: Between January 2006 and April 2010, of 48,626 women undergoing screening, 571 (1.2%) were diagnosed with ICC, including 262 (46%) HIV seropositive (median age: 35 years), 131 (23%) HIV seronegative (median age: 40 years), and 178 (31%) of unknown HIV serostatus (median age: 38 years). Among younger (≤35 years) women, being HIV seropositive was associated with a 4-fold higher risk of ICC [adjusted odds ratio = 4.1 (95% confidence interval: 2.8, 5.9)] than being HIV seronegative. The risk of ICC increased with increasing age among HIV-seronegative women and women with unknown HIV serostatus, but among HIV-seropositive women, the risk peaked around age 35 and nonsignificantly declined with increasing ages. Other factors related to ICC included being married (vs. being unmarried/widowed) in both younger and older women, and with having 2+ (vs. ≤1) lifetime sexual partners among younger women. CONCLUSIONS: HIV infection seems to have increased the risk of cervical cancer among younger women in Zambia, pointing to the urgent need for expanding targeted screening interventions.

Population-level scale-up of cervical cancer prevention services in a low-resource setting: development, implementation, and evaluation of the cervical cancer prevention program in Zambia.

BACKGROUND: Very few efforts have been undertaken to scale-up low-cost approaches to cervical cancer prevention in low-resource countries. METHODS: In a public sector cervical cancer prevention program in Zambia, nurses provided visual-inspection with acetic acid (VIA) and cryotherapy in clinics co-housed with HIV/AIDS programs, and referred women with complex lesions for histopathologic evaluation. Low-cost technological adaptations were deployed for improving VIA detection, facilitating expert physician opinion, and ensuring quality assurance. Key process and outcome indicators were derived by analyzing electronic medical records to evaluate program expansion efforts. FINDINGS: Between 2006-2013, screening services were expanded from 2 to 12 clinics in Lusaka, the most-populous province in Zambia, through which 102,942 women were screened. The majority (71.7%) were in the target age-range of 25-49 years; 28% were HIV-positive. Out of 101,867 with evaluable data, 20,419 (20%) were VIA positive, of whom 11,508 (56.4%) were treated with cryotherapy, and 8,911 (43.6%) were referred for histopathologic evaluation. Most women (87%, 86,301 of 98,961 evaluable) received same-day services (including 5% undergoing same-visit cryotherapy and 82% screening VIA-negative). The proportion of women with cervical intraepithelial neoplasia grade 2 and worse (CIN2+) among those referred for histopathologic evaluation was 44.1% (1,735/3,938 with histopathology results). Detection rates for CIN2+ and invasive cervical cancer were 17 and 7 per 1,000 women screened, respectively. Women with HIV were more likely to screen positive, to be referred for histopathologic evaluation, and to have cervical precancer and cancer than HIV-negative women. INTERPRETATION: We creatively disrupted the 'no screening' status quo prevailing in Zambia and addressed the heavy burden of cervical disease among previously unscreened women by establishing and scaling-up public-sector screening and treatment services at a population level. Key determinants for successful expansion included leveraging HIV/AIDS program investments, and context-specific information technology applications for quality assurance and filling human resource gaps.

Clinical performance of digital cervicography and cytology for cervical cancer screening in HIV-infected women in Lusaka, Zambia.

Although there is a growing literature on the clinical performance of visual inspection with acetic acid in HIV-infected women, to the best of our knowledge, none have studied visual inspection with acetic acid enhanced by digital cervicography. We estimated clinical performance of cervicography and cytology to detect cervical intraepithelial neoplasia grade 2 or worse. Sensitivity and specificity of cervicography were 84% [95% confidence interval (CI): 72 to 91) and 58% (95% CI: 52 to 64). At the high-grade squamous intraepithelial lesion or worse cutoff for cytology, sensitivity and specificity were 61% (95% CI: 48 to 72) and 58% (95% CI: 52 to 64). In our study, cervicography seems to be as good as cytology in HIV-infected women.

Utilization of cervical cancer screening services and trends in screening positivity rates in a 'screen-and-treat' program integrated with HIV/AIDS care in Zambia.

BACKGROUND: In the absence of stand-alone infrastructures for delivering cervical cancer screening services, efforts are underway in sub-Saharan Africa to dovetail screening with ongoing vertical health initiatives like HIV/AIDS care programs. Yet, evidence demonstrating the utilization of cervical cancer prevention services in such integrated programs by women of the general population is lacking. METHODS: We analyzed program operations data from the Cervical Cancer Prevention Program in Zambia (CCPPZ), the largest public sector programs of its kind in sub-Saharan Africa. We evaluated patterns of utilization of screening services by HIV serostatus, examined contemporaneous trends in screening outcomes, and used multivariable modeling to identify factors associated with screening test positivity. RESULTS: Between January 2006 and April 2011, CCPPZ services were utilized by 56,247 women who underwent cervical cancer screening with visual inspection with acetic acid (VIA), aided by digital cervicography. The proportion of women accessing these services who were HIV-seropositive declined from 54% to 23% between 2006-2010, which coincided with increasing proportions of HIV-seronegative women (from 22% to 38%) and women whose HIV serostatus was unknown (from 24% to 39%) (all p-for trend<0.001). The rates of VIA screening positivity declined from 47% to 17% during the same period (p-for trend <0.001), and this decline was consistent across all HIV serostatus categories. After adjusting for demographic and sexual/reproductive factors, HIV-seropositive women were more than twice as likely (Odds ratio 2.62, 95% CI 2.49, 2.76) to screen VIA-positive than HIV-seronegative women. CONCLUSIONS: This is the first 'real world' demonstration in a public sector implementation program in a sub-Saharan African setting that with successful program scale-up efforts, nurse-led cervical cancer screening programs targeting women with HIV can expand and serve all women, regardless of HIV serostatus. Screening program performance can improve with adequate emphasis on training, quality control, and telemedicine-support for nurse-providers in clinical decision making.

Implementation of cervical cancer prevention services for HIV-infected women in Zambia: measuring program effectiveness.

BACKGROUND: Cervical cancer kills more women in low-income nations than any other malignancy. A variety of research and demonstration efforts have proven the efficacy and effectiveness of low-cost cervical cancer prevention methods but none in routine program implementation settings of the developing world, particularly in HIV-infected women. METHODS: In our public sector cervical cancer prevention program in Zambia, nurses conduct screening using visual inspection with acetic acid aided by digital cervicography. Women with visible lesions are offered same-visit cryotherapy or referred for histologic evaluation and clinical management. We analyzed clinical outcomes and modeled program effectiveness among HIV-infected women by estimating the total number of cervical cancer deaths prevented through screening and treatment. RESULTS: Between 2006 and 2008, 6572 HIV-infected women were screened, 53.6% (3523) had visible lesions, 58.5% (2062) were eligible for cryotherapy and 41.5% (1461) were referred for histologic evaluation. A total of 75% (1095 out of 1462) of patients who were referred for evaluation complied. Pathology results from 65% (715 out of 1095) of women revealed benign abnormalities in 21% (151), cervical intraepithelial neoplasia (CIN) I in 30% (214), CIN 2/3 in 33% (235) and invasive cervical cancer in 16.1% (115, of which 69% were early stage). Using a conditional probability model, we estimated that our program prevented 142 cervical cancer deaths (high/low range: 238-96) among the 6572 HIV-infected women screened, or one cervical cancer death prevented per 46 (corresponding range: 28-68) HIV-infected women screened. CONCLUSION: Our prevention efforts using setting-appropriate human resources and technology have reduced morbidity and mortality from cervical cancer among HIV-infected women in Zambia. Financial support for implementing cervical cancer prevention programs integrated within HIV/AIDS care programs is warranted. Our prevention model can serve as the implementation platform for future low-cost HPV-based screening methods, and our results may provide the basis for comparison of programmatic effectiveness of future prevention efforts.