Michael L. Hicks

Implementation of 'see-and-treat' cervical cancer prevention services linked to HIV care in Zambia.

Greater than 80% of the worlds new cases and deaths due to cervical cancer occur in the developing world [1]. No more than 5% of women in these settings are screened for cervical cancer even once in their lifetimes [2]. Earlier attempts to establish population-based cervical cancer prevention programs using cytology screening in resource-limited settings have inevitably fallen short or failed [3–5]. Although many of the reasons for failure can be attributed to lack of resources and trained manpower, the multiple visit requirements of cytology-based screening programs jeopardizes success and sustainability.

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 programs implementation and integration with existing HIV/AIDS programs.

The National Cancer Data Base Report on Endometrial Carcinoma in African-American Women

Although the incidence of uterine carcinoma is lower among African‐American women compared with white women, the mortality rates are higher for African‐American patients. This report is part of an ongoing series on gynecologic malignancies in African‐American women.

The national cancer data base report on malignant epithelial ovarian carcinoma in African-American women

Epithelial ovarian carcinoma is the fifth most common cause of cancer death among African‐American women. Although the incidence rate of ovarian carcinoma for whites is higher than that for African Americans, the relative survival rate for African Americans is poorer.

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.

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

Abstract: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.

Gynecologic cancer among the socioeconomically disadvantaged

It is difficult to discern the true dimensions of the relationship between poverty and gynecologic cancer. In well designed studies of patients with gynecologic cancers, demographic stratification usually is performed based on race/ethnicity, age, or geographic locale, but not on economic class. The unstated assumption of many of these reports is that women of color, inhabitants of rural communities, and older women are all poor. Although it is true that these populations are overrepresented among the poor, unless the variable of economic class is specifically evaluated, the broad nature of the problem may go unappreciated: the status of gynecologic cancers among the poor is primarily a reflection of a deeply rooted structural problem in the U.S. economy, the reverberations of which are experienced by all women who cannot afford regular health care. When women are poor and have gynecologic cancers, they often seek orthodox health care only after the symptoms have become unbearable. Explanations of this phenomenon include underlying feelings of pessimism, fatalism, or low self‐esteem; faith in a belief system that does not regard the physician as the person to whom one goes for prevention or treatment of diseases; inaccessibility of health care facilities; experiences interpreted as degrading once health care facilities are accessed; high risk behavior and inability to pay.

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.

Monitoring the performance of “screen-and-treat” cervical cancer prevention programs

Over the past decade, “screen-and-treat” programs for cervical cancer prevention have been initiated across low- and middle-income countries [1,2]. Service utilization trends were analyzed from the Cervical Cancer Prevention Program in Zambia (CCPPZ) [3], the largest such program in sub-Saharan Africa. In CCPPZ, trained nurses provide digital cervicography-aided visual inspection with acetic acid (VIA)-based screening and immediate treatment by cryotherapy, and referral for histologic evaluation of advanced lesions. The study evaluated rates of “same day services” (numerator: VIA-positive women receiving same-day cryotherapy plus VIA-negative women receiving counseling and follow-up advice; denominator: total number of women screened) and “appropriate referrals” (numerator: women with histologically-confirmed precancerous cervical intraepithelial neoplasia [CIN] grade 2+ lesions; denominator: women undergoing histologic evaluation) during the program implementation period. Trends in the probability of these outcomes over time were calculated using the R-software 2.11.1. The University of Zambia Research Ethics Committee exempted this secondary data analysis from human subjects review and informed consent. Among 58 802 women undergoing initial or follow-up evaluation between January 2006 and April 2011, the vast majority (51 753, 88%) received “same-day services” (including 9867 [of 15 867 VIA-positive] receiving cryotherapy, and 41 886 VIA-negative). “Same-day service” provision increased significantly over time (P trend < 0.001); a woman screened in 2011 had 2.4 (95% CI, 2.1 – 2.7) times higher odds of receiving “same-day services” than someone screened in 2007 (Fig. 1, left panel). Out of 2840 women with histopathology results (punch biopsy or loop electrosurgical excision conducted during the referral visit), 1364 (48%) had CIN2+ diagnosis (“appropriate referral”). This proportion increased over time (P trend < 0.001); in 2011, a woman had 1.9 (95% CI, 1.5 – 2.6) times higher odds of receiving “appropriate referral” than someone referred in 2007 (Fig. 1, right panel). The probability curves fit with restricted cubic splines revealed discernible upward and downward shifts. The inflections largely coincided with program expansion (i.e. introduction of new nurses who had a relatively higher rate of referral than more experienced nurses). Fig. 1 Trends in performance of “screen-and-treat” services in the Cervical Cancer Prevention Program in Zambia (CCPPZ). The left panel depicts the predicted probability (and 95% confidence intervals) of “same day services,” while ... Relatively straightforward internal quality evaluation metrics (“same-day services” and “appropriate referrals”) can serve as proxies of programmatic outcome measures. Since secular declines in disease burden are unlikely over the short term, the finding of increasing odds of “appropriate referrals” and “same day services” can be attributed to refinement in programmatic performance with expansion of service delivery, largely aided by improved training and capacity building, but also the availability of distance consultation services via telemedicine support [4]. Complementing other quality assurance efforts, such evaluation metrics can be built into similar efforts being undertaken in other low- and middle-income countries.

A Phase II Evaluation of Brivanib in the Treatment of Persistent Or Recurrent Carcinoma of the Cervix: An NRG Oncology/Gynecologic Oncology Group Study

BACKGROUND Brivanib is an oral, tyrosine kinase inhibitor against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR). We studied its efficacy and tolerability in persistent or recurrent cervical cancer patients. METHODS Eligible patients had at least one prior cytotoxic regimen for recurrence and with measurable disease. Brivanib 800mg was administered orally every day (1cycle=28days) until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) >6months and objective tumor response. RESULTS Of 28 eligible and evaluable women enrolled, 11 (39%) had primary surgery and 25 (89%) had prior radiation. Eighteen (64%) received one prior cytotoxic treatment and 10 (36%) had 2 prior regimens. Twelve (43%) had >2cycles of brivanib with 4 (14%) receiving >10cycles (range: 1-20). Seven (25%) patients had PFS >6months (90% CI: 7.3%-33.9%). Two (7%) (90% CI: 1.3%-20.8%) patients had partial tumor response with duration of 8 and 22months and 12 (43%) had stable disease. The median PFS was 3.2months (90% CI: 2.1-4.4). The median overall survival was 7.9months (90% CI: 6.1-11.7). More common grade 3 adverse events were hypertension, anemia, hyponatremia, hyperglycemia, elevated liver enzymes, nausea, headache, and colon hemorrhage. Grade 4 adverse events included sepsis and hypertension. CONCLUSIONS Based on early results of this phase II trial, brivanib was well tolerated and demonstrated sufficient activity after first stage but trial was stopped due to lack of drug availability.