Infiltrating T-cell markers in cervical carcinogenesis: a systematic review and meta-analysis.

Funder: Intramural Research Program of the National Cancer Institute at the National Institutes of Health (Z01 CP010124-21).BACKGROUND: The host adaptive immune response helps determine which cervical HPV infections persist and progress to precancer and cancer, and systematic characterisation of T-cell infiltration would help inform key steps in cervical carcinogenesis. METHODS: A systematic review and meta-analysis were conducted of infiltrating T-cells in normal cervix, low-grade lesions, high-grade lesions, and invasive cancers including epithelial, stromal, and total tissue and the following markers: CD3, CD4, CD8, FoxP3, CD25, and the CD4:CD8 ratio. An additional qualitative review summarised longitudinal data on associations between infiltrating T-cells and cervical disease persistence, regression, progression, or prognosis. RESULTS: There were fewer CD3+, CD4+, and CD8+ cells in cervical lesions and more cells in cancers compared to normal epithelium. FoxP3 and CD25+ regulatory T-cell infiltration is high in persistent and precancerous lesions, and longitudinal data show improved outcomes with lower regulatory T-cell levels. CONCLUSIONS: Successful immune evasion may reduce T-cell infiltration in HPV infected and precancerous epithelium, while invasive cancers are highly immunogenic, and regulatory T-cell infiltration increases with cervical disease progression. Understanding these factors may have prognostic value and could aid in novel treatment development and clinical guidelines, but published data are highly heterogeneous and leave important gaps to be filled by future studies

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

A prospective, single-arm, open-label, non-randomized, phase IIa trial of a nonavalent prophylactic HPV vaccine to assess immunogenicity of a prime and deferred-booster dosing schedule among 9-11 year-old girls and boys - clinical protocol

Background Human papillomavirus (HPV) vaccines are indicated for the prevention of cancers and genital warts caused by vaccine-covered HPV types. Although the standard regimen requires a two or three-dose vaccine series, there is emerging data suggesting that a single dose of the bivalent or quadrivalent HPV vaccine generates persistently positive antibody titers. No similar data is yet available for the nonavalent HPV vaccine, currently the only HPV vaccine available in the United States. The overall objective of our study is to assess the stability and kinetics of antibody titers for 24months following a single dose of the nonavalent HPV vaccine among preteen girls and boys. Methods This is a prospective, single-arm, open-label, non-randomized, Phase IIa trial among 9-11year-old girls and boys to determine the immunogenicity after a single dose of the nonavalent HPV vaccine (GARDASIL (R) 9) over 24months, with a deferred booster dose at 24months and an optional booster at 30months after the first dose. Participants provide blood specimens at 6, 12, 18, 24, and 30months after the first dose. Serologic geometric mean titers (GMT) of the nine vaccine types (HPV 16/18/ 6/11/31/33/45/52/58) will be measured at each time point. The primary objective is to determine the stability of type-specific serologic GMT of HPV16 and HPV18 between the 6- vs. 12-month, 12- vs. 18-month, and 18- vs. 24-month visits. Secondary objectives are to determine the stability of type-specific serologic GMT of the other HPV types (HPV 6/11/31/33/45/52/58) between the visits and to assess safety and reactogenicity after each vaccine dose. Discussion Single dose HPV vaccination could simplify the logistics and reduce costs of HPV vaccination in the US and across the world. This study will contribute important immunogenicity data on the stability and kinetics of type-specific antibody titers and inform feasibility of the single dose HPV vaccination paradigm.National Cancer Institute [HHSN26100009, CA023074]Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Statin use and risk of hepatocellular carcinoma in a U.S. population

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) are medications widely prescribed to reduce cholesterol levels. Observational studies in high-risk populations, mostly in Asia, have suggested that statins are associated with a reduced risk of hepatocellular carcinoma (HCC). The current study sought to evaluate the association of statin use and HCC in a U.S.-based, low-risk, general population

The burden of cervical pre-cancer and cancer in HIV positive women in Zambia: a modeling study

Abstract Background HIV infection is associated with a higher incidence of precancerous cervical lesions and their progression to invasive cervical cancer (ICC). Zambia is a global epicenter of HIV and ICC, yet the overall burden of cervical pre-cancer [cervical intraepithelial neoplasia 3 (CIN3)] and ICC among its HIV positive adult female population is unknown. The objective of this study was to determine the burden of cervical disease among HIV positive women in Zambia by estimating the number with CIN3 and ICC. Methods We conducted a cross-sectional study among 309 HIV positive women attending screening in Lusaka (Zambia’s most populated province) to measure the cervical disease burden by visual inspection with acetic acid enhanced by digital cervicography (DC), cytology, and histology. We then used estimates of the prevalence of CIN3 and ICC from the cross-sectional study and Spectrum model-based estimates for HIV infection among Zambian women to estimate the burden of CIN3 and ICC among HIV positive women nationally. Results Over half (52 %) of the study participants screened positive by DC, while 45 % had cytologic evidence of high grade squamous intraepithelial lesions (SIL) or worse. Histopathologic evaluation revealed that 20 % of women had evidence of CIN2 or worse, 11 % had CIN3 or worse, and 2 % had ICC. Using the Spectrum model, we therefore estimate that 34,051 HIV positive women in Zambia have CIN3 and 7,297 have ICC. Conclusions The DC, cytology, and histology results revealed a large cervical disease burden in this previously unscreened HIV positive population. This very large burden indicates that continued scale-up of cervical cancer screening and treatment is urgently needed

HPV Prevalence and Cervical Intraepithelial Neoplasia among HIV-infected Women in Yunnan Province, China: A Pilot Study

To determine the prevalence of HPV and cervical neoplasia among HIV-infected women in southwestern China

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

We sought to investigate the progression of human papillomaviruses (HPV) infection in HIV-positive women after cryotherapy

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

BackgroundIn 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.MethodsWe 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.ResultsBetween 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.ConclusionsThis 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 and Operational Research: Age Distribution and Determinants of Invasive Cervical Cancer in a “Screen-and-Treat” Program Integrated With HIV/AIDS Care in Zambia

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