Dataset for the Reporting of Carcinoma of the Cervix: Recommendations From the International Collaboration on Cancer Reporting (ICCR).

Cervical carcinoma remains one of the most common cancers affecting women worldwide, despite effective screening programs being implemented in many countries for several decades. The International Collaboration on Cancer Reporting (ICCR) dataset for cervical carcinoma was first developed in 2017 with the aim of developing evidence-based standardized, consistent and comprehensive surgical pathology reports for resection specimens. This 4th edition update to the ICCR dataset on cervical cancer was undertaken to incorporate major changes based upon the updated International Federation of Obstetricians and Gynecologists (FIGO) staging for carcinoma of the cervix published in 2018 and the 5th Edition World Health Organization (WHO) Classification of Female Genital Tumors published in 2020 and other significant developments in pathologic aspects of cervical cancer. This updated dataset was developed by a panel of expert gynecological pathologists and an expert gynecological oncologist, with a period of open consultation. The revised dataset includes "core" and "noncore" elements to be reported; these are accompanied by detailed explanatory notes and references providing the rationale for the updates. Standardized reporting using datasets such as this helps facilitate consistency and accuracy, data collection across different sites and comparison of epidemiological and pathologic parameters for quality and research purposes.

Prevalence and Distribution of Vaccine-Preventable Genital Human Papillomavirus(HPV) Genotypes in Ghanaian Women Presenting for Screening.

BACKGROUND: Cervical cancer is the most common gynaecologic cancer in Ghana where it is also the second most common cause of all female cancers. A number of vaccines are available to provide both individual and population-level protection against persistent infection with high-risk human papillomaviruses (HR-HPV) and reduce the burden of cervical cancer. Data on the epidemiology of vaccine-preventable papillomaviruses in Ghana is scant. METHODS: A cross-sectional observational study was implemented from May 2011 to November 2014 to understand the epidemiology of genital human papillomavirus (HPV) genotypes and cervical dysplasia in the Greater Kumasi area of Ghana. A nested multiplex polymerase chain reaction (NMPCR) assay incorporating degenerate E6/E7 consensus primers and type-specific primers was used for the detection and typing of eighteen (18) HPV genotypes among women who had never attended cervical screening prior to this study. RESULTS: The general prevalence of HPV infection in Kumasi was 37.2%. The age-standardized prevalence was 40.9% overall. The frequency of HR-HPV genotypes present in decreasing order were HPV-52, -56, -35, -18, -58, -68, -51, -39, -45, -16, -59, -33 and -31. Low-risk HPVs were also detected in the following order: HPV-42, -43, -66, -6/11 and -44. CONCLUSIONS: The study shows that currently available prophylactic vaccines have the potential to be useful in the primary prevention of HPV infections in the country. This study strengthens the belief that prophylactic HPV vaccination could be a long-term strategy to reduce the burden of HPV infections and potentially reduce the burden of HPV-associated cancers and epithelial cell abnormalities among health-seeking women in Kumasi. Efforts to make vaccines available to young girls should be prioritized.

Self-Collected Specimens Revealed a Higher Vaccine- and Non-Vaccine-Type Human Papillomavirus Prevalences in a Cross-Sectional Study in Akuse.

BACKGROUND: Population-specific epidemiologic data on human Papillomavirus infection, which are limited in most of the SubSaharan African countries, are necessary for effective cervical cancer prevention. This study aimed to generate population-specific data on human Papillomavirus infections, and determine which of these, self-collected and provider-collected specimens, gives a higher estimate of the prevalence of human Papillomaviruses, including vaccine and non-vaccine-type human Papillomavirus. METHODS: In this cross-sectional study, following a questionnaire-based collection of epidemiological data, self-, and provider-collected specimens, obtained from women 15-65 years of age, were analysed for human Papillomavirus types by a nested-multiplex polymerase chain reaction, and for cervical lesions by Pap testing. HPV data were categorised according to risk type and vaccine types for further analysis. RESULTS: The difference between the overall human Papillomavirus infection prevalences obtained with the self-collected specimens, 43.1% (95% CI of 38.0-51.0%) and that with the provider-collected samples, 23.3% (95% CI of 19.0-31.0%) were significant (p ≤ 0.001). The prevalence of quadrivalent vaccine-type human Papillomaviruses was 12.3% with self-collected specimens, but 6.0% with provider-collected specimens. For the nonavalent vaccine-types, the prevalences were 26.6% and 16.7% respectively. There were multiple infections involving both vaccine-preventable and nonvaccine preventable high-risk human Papillomavirus genotypes. CONCLUSION: The Akuse subdistrict can, therefore, be said to have a high burden of human Papillomavirus infections, which included nonvaccine types, as detected with both self-collected and provider-collected specimens. These imply that self-collection is to be given a higher consideration as a means for a population-based high-risk human Papillomavirus infections burdens assessment/screening. Additionally, even with a successful implementation of the HPV vaccination, if introduced in Ghana, there is still the need to continue with the screening of women.

Prevalence of cervical cancer and pre-cancerous lesions among unscreened Women in Kumasi, Ghana.

Ghana does not have a universal population-based cervical cancer screening program and there is very limited information about the distribution of cervical epithelial cell lesions. This study provides evidence that a moderately high prevalence of cervical cancer and precancerous lesions exists among unscreened women in Kumasi.The prevalence of cervical epithelial cell abnormalities among a cross-section of women attending cervical cancer screening for the first time in a suburb of Ghana from 2011 to 2014 was studied. Cervical smears were prepared and examined independently by 2 cytotechnologists and confirmed by a pathologist. Cervical lesions were classified according to the Bethesda System for cervical cytology 2001.Out of the 592 women for whom a Pap smear was available for evaluation, 555 (93.8%) were negative for intraepithelial lesion or malignancy. Eight women (1.4%) showed atypical squamous cells of undetermined significance (ASCUS), 9 (1.4%) low-grade squamous intraepithelial lesions, and 2 (0.3%) high-grade squamous intraepithelial lesions. A total of 15 (2.5%) smears were unsatisfactory for cervical cytology. Additionally, 3 women (0.5%) had squamous cell carcinoma, giving an overall rate of 3.7% for epithelial cell abnormalities.Cervical cancer and precursor epithelial cell abnormalities are common among women in Kumasi for a disease that can be prevented by early detection through routine screening and management. This study provides adequate background data to recommend the implementation of cervical cancer screening in all eligible women in Ghana.

Dynamics of genotype-specific HPV clearance and reinfection in rural Ghana may compromise HPV screening approaches.

Persistent Human Papillomavirus (HPV) infection is a prerequisite for cervical cancer development. Few studies investigated clearance of high-risk HPV in low-and-middle-income countries. Our study investigated HPV clearance and persistence over four years in women from North Tongu District, Ghana. In 2010/2011, cervical swabs of 500 patients were collected and HPV genotyped (nested multiplex PCR) in Accra, Ghana. In 2014, 104 women who previously tested positive for high-risk HPV and remained untreated were re-tested for HPV. Cytobrush samples were genotyped (GP5+/6+ PCR & Luminex-MPG readout) in Berlin, Germany. Positively tested patients underwent colposcopy and treatment if indicated. Of 104 women, who tested high-risk HPV+ in 2010/2011, seven (6,7%; 95%CI: 2.7-13.4%) had ≥1 persistent high-risk-infection after ~4 years (mean age 39 years). Ninety-seven (93,3%; 95%CI: 86.6-97.3%) had cleared the original infection, while 22 (21.2%; 95%CI: 13.8-30.3%) had acquired new high-risk infections with other genotypes. Persistent types found were HPV 16, 18, 35, 39, 51, 52, 58, and 68. Among those patients, one case of CIN2 (HPV 68) and one micro-invasive cervical cancer (HPV 16) were detected. This longitudinal observational data suggest that single HPV screening rounds may lead to over-referral. Including type-specific HPV re-testing or additional triage methods could help reduce follow-up rates.

Data Set for the Reporting of Carcinomas of the Cervix: Recommendations From the International Collaboration on Cancer Reporting (ICCR).

A comprehensive pathologic report is essential for optimal patient management, cancer staging and prognostication. In many countries, proforma reports are used but the content of these is variable. The International Collaboration on Cancer Reporting is an alliance formed by the Royal Colleges of Pathologists of Australasia and the United Kingdom, the College of American Pathologists, the Canadian Partnership Against Cancer and the European Society of Pathology, for the purpose of developing standardized, evidence-based reporting data sets for each cancer site. This will reduce the global burden of cancer data set development and reduplication of effort by different international institutions that commission, publish and maintain standardized cancer-reporting data sets. The resultant standardization of cancer-reporting benefits not only those countries directly involved in the collaboration but also others not in a position to develop their own data sets. We describe the development of an evidence-based cancer data set by the International Collaboration on Cancer Reporting expert panel for the reporting of primary cervical carcinomas and present the "required" and "recommended" elements to be included in the pathology report as well as an explanatory commentary. This data set encompasses the International Federation of Obstetricians and Gynaecologists and Union for International Cancer Control staging systems for cervical neoplasms and the updated World Health Organization classification of gynecologic tumors. The data set also addresses controversial issues such as tumor grading and measurement, including measurement of multifocal carcinomas. The widespread implementation of this data set will facilitate consistent and accurate data collection, comparison of epidemiological and pathologic parameters between different populations, facilitate research, and hopefully result in improved patient management.

A tailored within-community specimen collection strategy increased uptake of cervical cancer screening in a cross-sectional study in Ghana.

BACKGROUND: The implementation of cervical cancer screening strategies has reported different rates of success in different countries due to population specific factors that limit women's participation. We report observations and the development of a community-based specimen collection strategy which resulted from interactions with women in the study communities, following an initial low response to a hospital based cervical cancer screening strategy. METHOD: Women were recruited by a house survey and invited to report at a hospital either within a week or after a week for self and health-personnel specimen collections. However, due to the very low response and subsequent interactions with the women of the communities, another strategy was developed that required recruited women report at a central location within their respective communities for specimen collections at times that did not interfere with their daily routines. RESULTS: For specimen collection, of the 156 participants who opted to report after a week at the hospital, 60 (38.5%) reported. Of the 118 participants who opted to report within 1 week at the hospital, 55 (46.6%) reported. Of the 103 participants were invited to report at a specified location within the community, 98 (95.1%) reported. An overall response rate of 60.4% was attained. Almost 89.7% (226 of 253) of the women performed both self and health personnel sample collection. CONCLUSION: The community-based strategy with self-specimen collection and HPV testing holds great potential for increasing women's participation in cervical cancer screening in Ghana as compared to the hospital based strategy.

Helicobacter pylori cagA and vacA genes in dyspeptic Ghanaian patients.

BACKGROUND: Helicobacter pylori infection is prevalent in Ghana. The development of gastro-duodenal disease is dependent on virulence of the infecting strain, host susceptibility and environmental factors. Helicobacter pylori cagA and vacA strains induce more inflammation, ulceration and oncogenesis. Here, for the first time we present data on H. pylori cagA and vacA genes and their association with gastro-duodenal disease in Ghana. A total of 159 patients with dyspepsia at Korle-Bu Teaching Hospital, Accra, were investigated for H. pylori with urease-CLO, of which 113 (71.1%) were positive. Genomic DNA was extracted from antral biopsies using QIAGEN DNeasy kit. Detection of H. pylori vacA and cagA genes were determined by PCR as previously described. RESULTS: In total, 110 (69.2%) vacAs1, 71 (44.7%) vacAm1, 35 (22.0%) vacAm2, 77 (48.4%) cagA-(hydrophilic region) and 109 (68.6%) cagA-(internal duplication region) were detected. In multivariate analysis, duodenal ulcer was more likely than other diagnoses to have detectable cagA-(hydrophilic region) (OR 3.1 CI 1.2-7.9) or vacAs1m1 (OR 6.5 CI 1.2-34.0). CONCLUSIONS: Majority of biopsies were colonized with H. pylori harboring both cagA and vacA. H. pylori cagA-(internal duplication region) was more prevalent than cagA-(hydrophilic region). Duodenal ulcer was more likely than other diagnoses to have detectable cagA-(hydrophilic region) or vacAs1m1.

Differences in age-specific HPV prevalence between self-collected and health personnel collected specimen in a cross-sectional study in Ghana.

BACKGROUND: HPV infections are ubiquitous and particularly common among sexually active young women. However, there are regional and national variations in age-specific HPV prevalence, which have implications for cervical cancer control. Data on age-specific HPV prevalences for Ghana and most sub-Saharan countries are scanty. Therefore, this study primarily sought to determine the age-specific HPV prevalence among women in a Ghanaian community and to determine whether these prevalences determined with health-personnel and self-collected specimens were comparable. METHODS: In this cross-sectional study, conducted between March 2012 and March 2013, cervical specimens were collected by self- and health-personnel collection from 251 women who were between the ages of 15 and 65 years. HPV present in these specimens were genotyped by a nested-multiplex PCR and Luminex fluoro-microspheres based method. Information on the demographic, sexual and reproductive characteristics of the women were also obtained. A Chi-square test of association was employed to determine the association of the distribution of age groups with each categorised sexual and reproductive characteristic and HPV risk type's status. RESULTS: The age group distribution of the participants was significantly associated with overall (χ2 = 36.1; p = 0.001), high risk (χ2 = 26.09; p = 0.002) and low risk (χ2 = 21.49; p = 0.011) HPV prevalences. The age-specific HPV prevalence pattern for each of the HPV risk types, determined with self-collected specimen, showed three peaks (at 20-24 years; 40-44 years and ≥ 55 years), while those determined with health-personnel collected specimen, showed two peaks (at 20-24 years and ≥ 55 years) for each HPV risk type's prevalence pattern. The high risk HPV prevalences determined with self-collected specimen were often higher than those determined with health-personnel specimen for the age groups between 25 and 45 years, who are mostly targeted for screening by HPV testing. Additionally, there were interesting variations in patterns of age-specific HPV genotype-specific prevalence between the two specimen collection methods. CONCLUSIONS: The usefulness of self-collected specimen for high risk HPV burden determination and the existence of a two peaked and three peaked age-specific HPV prevalences in Ghana have been clearly indicated.

Unique LCR variations among lineages of HPV16, 18 and 45 isolates from women with normal cervical cytology in Ghana.

BACKGROUND: In addition to being useful for classification, sequence variations of human Papillomavirus (HPV) genotypes have been implicated in differential oncogenic potential and a differential association with the different histological forms of invasive cervical cancer. These associations have also been indicated for HPV genotype lineages and sub-lineages. In order to better understand the potential implications of lineage variation in the occurrence of cervical cancers in Ghana, we studied the lineages of the three most prevalent HPV genotypes among women with normal cytology as baseline to further studies. METHODS: Of previously collected self- and health personnel-collected cervical specimen, 54, which were positive for HPV16, 18 and 45, were selected and the long control region (LCR) of each HPV genotype was separately amplified by a nested PCR. DNA sequences of 41 isolates obtained with the forward and reverse primers by Sanger sequencing were analysed. RESULTS: Nucleotide sequence variations of the HPV16 genotypes were observed at 30 positions within the LCR (7460 - 7840). Of these, 19 were the known variations for the lineages B and C (African lineages), while the other 11 positions had variations unique to the HPV16 isolates of this study. For the HPV18 isolates, the variations were at 35 positions, 22 of which were known variations of Africa lineages and the other 13 were unique variations observed for the isolates obtained in this study (at positions 7799 and 7813). HPV45 isolates had variations at 35 positions and 2 (positions 7114 and 97) were unique to the isolates of this study. CONCLUSION: This study provides the first data on the lineages of HPV 16, 18 and 45 isolates from Ghana. Although the study did not obtain full genome sequence data for a comprehensive comparison with known lineages, these genotypes were predominately of the Africa lineages and had some unique sequence variations at positions that suggest potential oncogenic implications. These data will be useful for comparison with lineages of these genotypes from women with cervical lesion and all the forms of invasive cervical cancers.

Factors associated with gastro-duodenal disease in patients undergoing upper GI endoscopy at the Korle-Bu Teaching Hospital, Accra, Ghana.

BACKGROUND: There is a high prevalence of gastro-duodenal disease in sub-Saharan Africa. Peptic ulcer disease in dyspeptic patients, 24.5%, was comparable to prevalence of gastro-duodenal disease among symptomatic individuals in developed countries (12 - 25%). Limited data exists regarding its associated risk factors despite accumulating evidence indicating that gastroduodenal disease is common in Ghana. OBJECTIVES: This study investigates risk factors associated with gastro-duodenal disease at the Korle-Bu Teaching Hospital, Accra, Ghana. METHODS: This study utilized a cross-sectional design to consecutively recruit patients referred with upper gastro-intestinal symptoms for endoscopy. The study questionnaire was administered to study participants. Helicobacter pylori infection was confirmed by rapid-urease examination at endoscopy. RESULTS: Of 242 patients sampled; 64 had duodenal ulcer, 66 gastric ulcer, 27gastric cancer and 64 non-ulcer dyspepsia. Nineteen (19) had duodenal and gastric ulcer while 2 had gastric ulcer and cancer. A third (32.6%) of patients had history of NSAID-use. H. pyloriwas associated with gastric ulcer (p=0.033) and duodenal ulcer (p=0.001). There was an increased prevalence of duodenal ulcer in H. pylori-infected patients taking NSAIDs, P=0.003. CONCLUSION: H. pylori was a major risk factor for peptic ulcer disease. However, NSAID-related gastro-duodenal injury has been shown to be common in H. pylori infected patients. It highlights the need for awareness of the adverse gastro-intestinal effects in a H. pylori endemic area.

Acute toxicity studies of Croton membranaceus root extract.

AIM OF THE STUDY: Croton membranaceus root and leaf extracts are used in the Bahamas to aromatize tobacco, in Nigeria to improve digestion, and in Ghana, for benign prostate hyperplasia. Despite claims of success there is paucity of information on its toxicity. The aim of this study was to determine if Croton membranaceus has acute toxicity properties. MATERIALS AND METHODS: Roots were air-dried in a solar dryer for one week before milling. The powder was extracted with 96% ethanol, freeze-dried and re-extracted with distilled water and freeze-dried. 15 male Sprague-Dawley rats (180-200 g) were divided equally into 2 treatment groups [low dose (LD) and high dose (HD)], plus a control group (C). LD and HD received 1500 and 3000 mg/kg b.wt. Croton membranaceus aqueous extract, respectively, one time and observed for 14 days. Haematological [Full Blood Count and haemoglobin (Hb)], biochemical [bilirubin, alanine aminotransferase (ALA), aspartate aminotransferase (AST), total protein, albumin, globulin, alkaline phosphatise (ALP), γ-glutamyltranspetidase (GGT), urea, creatinine, creatinine kinase - Muscle and Brain (CK-MB), creatinine kinase - Total (CK-R)] examinations were performed. RESULTS: Control group's CK-MB (5444±534 U/L) and LD group CK-MB (4014±1016 U/L) were significantly different (p<0.05). Control and the HD group CK-MB (3955±1135 U/L) were significantly different (p<0.05). Both LD and HD CK-R levels (697±197U/L and 732±203 U/L, respectively), were lower than the control (1139±220 U/L) at 48 h and 14 days (p<0.05, p<0.05, respectively). γ-GT levels of the HD group was 4.8±0.4 U/L compared to the Control group value of 0.9±0.2 U/L (p<0.05). CONCLUSIONS: Taking all factors into consideration, Croton membranaceus ingestion does not produce general acute toxicity. However, its creatinine kinase lowering ability could be explored.

Cerebrospinal fluid and serum biomarkers of cerebral malaria mortality in Ghanaian children.

BACKGROUND: Plasmodium falciparum can cause a diffuse encephalopathy known as cerebral malaria (CM), a major contributor to malaria associated mortality. Despite treatment, mortality due to CM can be as high as 30% while 10% of survivors of the disease may experience short- and long-term neurological complications. The pathogenesis of CM and other forms of severe malaria is multi-factorial and appear to involve cytokine and chemokine homeostasis, inflammation and vascular injury/repair. Identification of prognostic markers that can predict CM severity will enable development of better intervention. METHODS: Postmortem serum and cerebrospinal fluid (CSF) samples were obtained within 2-4 hours of death in Ghanaian children dying of CM, severe malarial anemia (SMA), and non-malarial (NM) causes. Serum and CSF levels of 36 different biomarkers (IL-1beta, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, Eotaxin, FGF basic protein, CRP, G-CSF, GM-CSF, IFN-gamma, TNF-alpha, IP-10, MCP-1 (MCAF), MIP-1alpha, MIP-1beta, RANTES, SDF-1alpha, CXCL11 (I-TAC), Fas-ligand [Fas-L], soluble Fas [sFas], sTNF-R1 (p55), sTNF-R2 (p75), MMP-9, TGF-beta1, PDGF bb and VEGF) were measured and the results compared between the 3 groups. RESULTS: After Bonferroni adjustment for other biomarkers, IP-10 was the only serum biomarker independently associated with CM mortality when compared to SMA and NM deaths. Eight CSF biomarkers (IL-1ra, IL-8, IP-10, PDGFbb, MIP-1beta, Fas-L, sTNF-R1, and sTNF-R2) were significantly elevated in CM mortality group when compared to SMA and NM deaths. Additionally, CSF IP-10/PDGFbb median ratio was statistically significantly higher in the CM group compared to SMA and NM groups. CONCLUSION: The parasite-induced local cerebral dysregulation in the production of IP-10, 1L-8, MIP-1beta, PDGFbb, IL-1ra, Fas-L, sTNF-R1, and sTNF-R2 may be involved in CM neuropathology, and their immunoassay may have potential utility in predicting mortality in CM.

Cancer mortality patterns in Ghana: a 10-year review of autopsies and hospital mortality.

BACKGROUND: Cancer mortality pattern in Ghana has not been reviewed since 1953, and there are no population-based data available for cancer morbidity and mortality patterns in Ghana due to the absence of a population-based cancer registry anywhere in the country. METHODS: A retrospective review of autopsy records of Department of Pathology, and medical certificate of cause of death books from all the wards of the Korle-Bu Teaching Hospital (KBTH), Accra, Ghana during the 10-year period 1991-2000 was done. RESULTS: The present study reviews 3659 cancer deaths at the KBTH over the 10-year period. The male-to-female ratio was 1.2:1. The mean age for females was 46.5 [Standard Deviation (SD), 20.8] years, whilst that of males was 47.8 (SD, 22.2) years. The median age was 48 years for females and 50 years for males. Both sexes showed a first peak in childhood, a drop in adolescence and young adulthood, and a second peak in the middle ages followed by a fall in the elderly, with the second peak occurring a decade earlier in females than in males. The commonest cause of cancer death in females was malignancies of the breast [Age-Standardized Cancer Ratio (ASCAR), 17.24%], followed closely by haematopoietic organs (14.69%), liver (10.97%) and cervix (8.47%). Whilst in males, the highest mortality was from the liver (21.15%), followed by prostate (17.35%), haematopoietic organs (15.57%), and stomach (7.26%). CONCLUSION: Considering the little information available on cancer patterns in Ghana, this combined autopsy and death certification data from the largest tertiary hospital is of considerable value in providing reliable information on the cancer patterns in Ghana.