HPV DNA Testing and Mobile Colposcopy for Cervical Precancer Screening in HIV Positive Women: A Comparison Between Two Settings in Ghana and Recommendation for Screening.

INTRODUCTION: Women living with HIV (WLHIV) have higher prevalence and persistence rates of high-risk human papillomavirus (hr-HPV) infection with a six-fold increased risk of cervical cancer. Thus, more frequent screening is recommended for WLHIV. OBJECTIVES: This retrospective descriptive cross-sectional study was conducted to investigate and compare the prevalence of hr-HPV infection and abnormal findings on mobile colposcopy in two cohorts of WLHIV following cervical screening in rural and urban settings in Ghana. METHODS: Through the mPharma 10 000 Women Initiative, WLHIV were screened via concurrent hr-HPV DNA testing (MA-6000; Sansure Biotech Inc., Hunan, China) and visual inspection (Enhanced Visual Assessment [EVA] mobile colposcope; MobileODT, Tel Aviv, Israel) by trained nurses. The women were screened while undergoing routine outpatient reviews at HIV clinics held at the Catholic Hospital, Battor (rural setting) and Tema General Hospital (urban setting), both in Ghana. RESULTS: Two-hundred and fifty-eight WLHIV were included in the analysis (rural, n = 132; urban, n = 126). The two groups were comparable in terms of age, time since HIV diagnosis, and duration of treatment for HIV. The hr-HPV prevalence rates were 53.7% (95% CI, 45.3-62.3) and 48.4% (95% CI, 39.7-57.1) among WLHIV screened in the rural vs urban settings (p-value = .388). Abnormal colposcopy findings were found in 8.5% (95% CI, 5.1-11.9) of the WLHIV, with no significant difference in detection rates between the two settings (p-value = .221). Three (13.6%) of 22 women who showed abnormal colposcopic findings underwent loop electrosurgical excision procedure (LEEP), leaving 19/22 women from both rural and urban areas with pending treatment/follow-up results, which demonstrates the difficulty faced in reaching early diagnosis and treatment, regardless of their area of residence. Histopathology following LEEP revealed CIN III in 2 WLHIV (urban setting, both hr-HPV negative) and CIN I in 1 woman in the rural setting (hr-HPV positive). CONCLUSIONS: There is a high prevalence of hr-HPV among WLHIV in both rural and urban settings in this study in Ghana. Concurrent HPV DNA testing with a visual inspection method (colposcopy/VIA) reduces loss to follow-up compared to performing HPV DNA testing as a standalone test and recalling hr-HPV positive women for follow up with a visual inspection method. Concurrent HPV DNA testing and a visual inspection method may also pick up precancerous cervical lesions that are hr-HPV negative and may be missed if HPV DNA testing is performed alone.

HPV18 L1 and long control region sequences variation and E6/E7 differential expression in nasopharyngeal and cervical cancers: a comparative study.

BACKGROUND: The role of high-risk human papillomaviruses (hr-HPVs) in cervical cancer (CC) pathogenesis has long been established. Knowledge about the involvement of hr-HPVs in the etiology of nasopharyngeal cancers (NPC) was not well appreciated until the early 2000s when a clear link began to emerge. However, it is not clear whether HPV oncogenesis in the different epithelial cancers is associated with L1 gene and long-control region (LCR) sequences variation. This study aimed to investigate the HPV18 L1 gene and LCR sequences variation in cervical and nasopharyngeal biopsies, and assessed E6 and E7 genes expression level in both cancers. METHOD: Four-hundred and three (403) formalin-fixed paraffin-embedded tissues originating from nasopharyngeal (NPC) (279) and cervical (CC) (124) sites were collected from a pathology laboratory, Pathologist Without Borders, Accra, Ghana. Haematoxylin and eosin staining was carried out to confirm the presence of cancer on prepared biopsy sections. DNA was extracted from the confirmed cancer biopsies, followed by PCR using MY09/GP5+ /6+ primers to detect the presence of HPV and specific primers for the amplification of L1 gene and LCR. Sanger sequencing was carried out to determine HPV genotypes, and L1 and LCR sequences variant of HPV18s in CC and NPC biopsies. The HPV18 E6/E7 mRNA expression pattern in both cancers was determined using RT-qPCR. RESULTS: Most of the NPC (45%) and CC (55%) biopsies were HPV18 positive. Comparison of HPV18 L1 sequences obtained from cervical and nasopharyngeal cancer tissues, the L1 sequences from the NPC were highly dissimilar with a 59-100% variation among themselves, and in relation to the reference strains. However, the L1 sequences from the CC were more similar with a 91.0-100% variation among the amplified sequences. Also, the LCR sequences from CC were quite different relative to that of NPC. Results for the differential expression of E6/E7 in the two cancers showed a higher fold change in E6 expression in the CC tissues than the NPC tissues while a reverse expression pattern was found for E7 gene. CONCLUSION: The current study reports for the first-time variations in HPV18 L1 and LCR sequences, and differential expression of E6/E7 genes in NPC compared to CC, suggesting a possible adaptation mechanism of the virus at different cancer sites.

Health-related quality of life among cervical cancer survivors at a tertiary hospital in Ghana.

INTRODUCTION: Cervical cancer is the second most common female cancer in Ghana. The disease and its treatment significantly affect survivors' health-related quality of life (HRQoL). We determined the overall quality of life (QoL) and identified its predictors among cervical cancer survivors after treatment. MATERIALS AND METHODS: A hospital-based cross-sectional analytical study was conducted on 153 disease-free cervical cancer survivors who completed curative treatment between January 2004 and December 2018 at Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana. We used the European Organization for Research and Treatment of Cancer core-30 item (EORTC QLQ-C30) and cervical cancer module (EORTC QLQ-CX24) to assess the survivors' overall QoL. QoL domain scores were dichotomised as affected or unaffected by disease and its treatment. Significant differences between the affected and unaffected groups within each QoL domain were determined using the student T-test. We used Kruskal-Wallis and Dunn's tests to examine the difference in QoL domains between treatment types, with significance based on Bonferroni corrections. Multivariable logistic regression was performed to identify predictors of overall QoL. A p-value of less than 0.05 was considered statistically significant. RESULTS: One hundred and fifty-three (153) women having a mean age of 58.3 (SD 11.4) years were studied. The overall QoL score was 79.6 (SD 16.0), and 74.5% of survivors reported good QoL score within the median follow up time of 41.8 months (interquartile range [IQR], 25.5-71.1 months) after cervical cancer diagnosis. Although the majority (66.0-84.3%) of the QoL functioning scale were unaffected, about a fifth (22.2%) to a third (34.5%) of the subjects had perceptual impairment in cognitive and role functioning. Financial difficulties, peripheral neuropathy and pain were most common symptoms reported as affected. A third of the survivors were worried that sex would be painful, and 36.6% indicated that their sexual activity as affected. The overall QoL scores for survivors who had surgery, chemoradiation and radiation-alone were 86.1 (SD 9.7), 76.9 (SD 17.7), and 80.7 (SD 14.7), respectively (p = 0.025). The predictors of survivor's overall QoL were loss of appetite [Adjusted Odd Ratio (AOR) = 9.34, 95% Confidence Interval (CI) = 2.13-35.8, p = 0.001], pain (AOR = 3.53, 95% CI = 1.25-9.31, p = 0.017) and body image (AOR = 5.89, 95% CI = 1.80-19.27, p = 0.003). CONCLUSION: About 75% of the survivors had a good overall quality of life. Primary surgical treatment affords the best prospects for quality of life with the least symptom complaints and financial burden. Loss of appetite, pain or diminution in body image perception predicted the overall quality of life of cervical cancer survivors after treatment.

Mobile colposcopy by trained nurses in a cervical cancer screening programme at Battor, Ghana.

Objectives: Cervical precancer screening programs are difficult to establish in low resource settings partly because of a lack of human resource. Our aiming was to overcome this challenge. We hypothesized that this could be done through task shifting to trained nurses. Design: Descriptive retrospective cross-sectional review. Setting: Training was at the Cervical Cancer Prevention and Training Center (CCPTC) and screening was carried out at the clinic and at outreaches / peripheral facilities. Participants: All women who reported to the clinic for screening or were recruited during outreaches. Interventions: All 4 nurses were trained for at least 2weeks (module 1). A total of 904 women were screened by the trained nurses using the EVA system. Quality assurance was ensured. Main outcome measures: Primary screening and follow-up were carried out by the trained nurses with quality assured through image sharing and meetings with peers and experienced gynaecologists. Results: 828 women had primary screening and 76 had follow-up screening. 739 (89.3%) were screened at the clinic and 89 (10.7%) at outreaches/peripheral facilities. Of all screened, 130 (14.5%) had cervical lesions, and 25 (2.8%) were treated, 12 (48.0%) by Loop Electrosurgical Excision Procedure (LEEP) performed by a gynaecologist, 11 (44.0%) with thermal coagulation by trained nurses except one, and 2 (8.0%) with cryotherapy by trained nurses. Conclusion: We demonstrate the utility of a model where nurses trained in basic colposcopy can be used to successfully implement a cervical precancer screening and treatment program in low-resource settings. Funding: None indicated.

Application of the hub and spokes model in improving access to cervical cancer screening in Ghana.

Objective: To examine the contribution of lower-level health facilities in increasing access to cervical cancer screening in the North Tongu District. Design: A descriptive cross-sectional study design was used. The Cervical Cancer Prevention and Training Centre (CCPTC) of the Catholic Hospital, Battor, served as the hub, and six health facilities (3 health centres and 3 CHPS compounds) served as the spokes. From April 2018 to September 2019, the well-resourced CCPTC trained 6 nurses at selected Community-based Health Planning and Services (CHPS) / Health Centres (HCs) (spokes) to provide cervical cancer screening services. The nurses, after training, started screening with VIA and HPV DNA testing. Participants: A total of 3,451women were screened by the trained nurses. This comprised 1,935 (56.1%) from the hub and 1,516 (43.9%) from the spokes. Main outcome measure: The detection of screen positives. Results: The screen positives were 19.4% (375/1935) at the hub and 4.9% (74/1516) at the spokes. Conclusion: We have demonstrated that a hub and spokes model for cervical cancer screening is possible in limited resource settings. Designating and resourcing a 'hub' that supports a network of 'spokes' could increase women's access to cervical cancer screening. This approach could create awareness about cervical cancer screening services and how they can be accessed. Funding: None declared.

Application of the hub and spokes model in improving access to cervical cancer screening in Ghana

Objective: To examine the contribution of lower-level health facilities in increasing access to cervical cancer screening in the North Tongu District. Design: A descriptive cross-sectional study design was used. The Cervical Cancer Prevention and Training Centre (CCPTC) of the Catholic Hospital, Battor, served as the hub, and six health facilities (3 health centres and 3 CHPS compounds) served as the spokes. From April 2018 to September 2019, the well-resourced CCPTC trained 6 nurses at selected Community-based Health Planning and Services (CHPS) / Health Centres (HCs) (spokes) to provide cervical cancer screening services. The nurses, after training, started screening with VIA and HPV DNA testing. Participants: A total of 3,451women were screened by the trained nurses. This comprised 1,935 (56.1%) from the hub and 1,516 (43.9%) from the spokes. Main outcome measure: The detection of screen positives Results: The screen positives were 19.4% (375/1935) at the hub and 4.9% (74/1516) at the spokes. Conclusion: We have demonstrated that a hub and spokes model for cervical cancer screening is possible in limited resource settings. Designating and resourcing a 'hub' that supports a network of 'spokes' could increase women's access to cervical cancer screening. This approach could create awareness about cervical cancer screening services and how they can be accessed

Mobile colposcopy by trained nurses in a cervical cancer screening programme at Battor, Ghana

Objectives: Cervical precancer screening programs are difficult to establish in low resource settings partly because of a lack of human resource. Our aiming was to overcome this challenge. We hypothesized that this could be done through task shifting to trained nurses. Design: Descriptive retrospective cross-sectional review. Setting: Training was at the Cervical Cancer Prevention and Training Center (CCPTC) and screening was carried out at the clinic and at outreaches / peripheral facilities.Participants: All women who reported to the clinic for screening or were recruited during outreaches Interventions: All 4 nurses were trained for at least 2weeks (module 1). A total of 904 women were screened by the trained nurses using the EVA system. Quality assurance was ensured. Main outcome measures: Primary screening and follow-up were carried out by the trained nurses with quality assured through image sharing and meetings with peers and experienced gynaecologists. Results: 828 women had primary screening and 76 had follow-up screening. 739 (89.3%) were screened at the clinic and 89 (10.7%) at outreaches/peripheral facilities. Of all screened, 130 (14.5%) had cervical lesions, and 25 (2.8%) were treated, 12 (48.0%) by Loop Electrosurgical Excision Procedure (LEEP) performed by a gynaecologist, 11 (44.0%) with thermal coagulation by trained nurses except one, and 2 (8.0%) with cryotherapy by trained nurses. Conclusion: We demonstrate the utility of a model where nurses trained in basic colposcopy can be used to successfully implement a cervical precancer screening and treatment program in low-resource settings

COVID-19 autopsy reports from the Ga-East Municipal and the 37 Military Hospitals in Accra, Ghana.

INTRODUCTION: Since the declaration of COVID-19 by the World Health Organisation (WHO) as a global pandemic on 11th March 2020, the number of deaths continue to increase worldwide. Reports on its pathologic manifestations have been published with very few from the Sub-Saharan African region. This article reports autopsies on COVID-19 patients from the Ga-East and the 37 Military Hospitals to provide pathological evidence for better understanding of COVID-19 in Ghana. METHODS: Under conditions required for carrying out autopsies on bodies infected with category three infectious agents, with few modifications, complete autopsies were performed on twenty patients with ante-mortem and/or postmortem RT -PCR confirmed positive COVID-19 results, between April and June, 2020. RESULTS: There were equal proportion of males and females. Thirteen (65%) of the patients were 55years or older with the same percentage (65%) having Type II diabetes and/or hypertension. The most significant pathological feature found at autopsy was diffuse alveolar damage. Seventy per cent (14/20) had associated thromboemboli in the lungs, kidneys and the heart. Forty per cent (6/15) of the patients that had negative results for COVID-19 by the nasopharyngeal swab test before death had positive results during postmortem using bronchopulmonary specimen. At autopsy all patients were identified to have pre-existing medical conditions. CONCLUSION: Diffuse alveolar damage was a key pathological feature of deaths caused by COVID-19 in all cases studied with hypertension and diabetes mellitus being major risk factors. Individuals without co-morbidities were less likely to die or suffer severe disease from SARS-CoV-2. FUNDING: None declared.

COVID-19 autopsies from the Ga-East municipal and the 37 military hospitals, Accra, Ghana

Introduction: Since the declaration of COVID-19 by the World Health Organisation (WHO) as a global pandemic on 11th March 2020, the number of deaths continue to increase worldwide. Reports on its pathologic manifestations have been published with very few from the Sub-Saharan African region. This article reports autopsies on COVID19 patients from the Ga-East and the 37 Military Hospitals to provide pathological evidence for better understanding of COVID-19 in Ghana. Methods: Under conditions required for carrying out autopsies on bodies infected with category three infectious agents, with few modifications, complete autopsies were performed on twenty patients with ante-mortem and/or postmortem RT -PCR confirmed positive COVID 19 results, between April and June ,2020. Results: There were equal proportion of males and females. Thirteen (65%) of the patients were 55years or older with the same percentage (65%) having Type II diabetes and/or hypertension. The most significant pathological feature found at autopsy was diffuse alveolar damage. Seventy per cent (14/20) had associated thromboemboli in the lungs, kidneys and the heart. Forty per cent (6/15) of the patients that had negative results for COVID-19 by the nasopharyngeal swab test before death had positive results during postmortem using bronchopulmonary specimen. At autopsy all patients were identified to have pre-existing medical conditions. Conclusion: Diffuse alveolar damage was a key pathological feature of deaths caused by COVID-19 in all cases studied with hypertension and diabetes mellitus being major risk factors. Individuals without co-morbidities were less likely to die or suffer severe disease from SARS-CoV-2

Epidemiology of cervical human papillomavirus (HPV) infection and squamous intraepithelial lesions (SIL) among a cohort of HIV-infected and uninfected Ghanaian women.

BACKGROUND: There is limited data in Ghana on the epidemiology of HPV and cervical neoplasia and their associations with HIV. This study aimed to compare among HIV-1 seropositive and HIV-seronegative Ghanaian women: (1) the prevalence, genotype distribution and risk factors associated with cervical HPV infection; and (2) the prevalence and risk factors associated with abnormal cervical cytology. METHODS: A comparative frequency-matched study was conducted in a systematic sample of women aged ≥18 years attending HIV and general outpatient clinics in Cape Coast Teaching Hospital, Ghana. Participants were interviewed and cervical samples collected for HPV genotyping (Seegene Anyplex-II HPV28) and cytological testing. RESULTS: Overall, 333 women were recruited, 163 HIV-1 seropositive and 170 HIV-seronegative women of mean age 43.8 years (SD ±9.4)) and 44.3 years (SD ±12.8), respectively. The prevalence of 14 high-risk (hr) HPV genotypes was higher among HIV-1 seropositive women (65.6% vs. 30.2%, P < 0.0001), as was proportion with multiple hr.-HPV infections (60.6% vs. 21.3%, P < 0.0001). HPV35 was the most prevalent hr.-HPV genotype in both groups (11.9% and 5.3%). The main factors associated with hr.-HPV infection were age for HIV-positive women and circumcision status of main sexual partner for both HIV-negative and positive women. Abnormal cervical cytology prevalence was higher among HIV-1 seropositive women (any SIL: 14.1% vs. 1.2%, P < 0.0001; low-grade SIL [LSIL]: 4.9% vs. 0.6%, P = 0.02; high-grade SIL: 1.8% vs. 0%, P = 0.07). Among HIV-1 seropositive women, number of pregnancies and CD4+ cell count were associated with LSIL+ cytology. There was strong association between LSIL+ abnormalities and HPV35 (aOR = 4.7, 95%CI: 1.3-17.7, P = 0.02). CONCLUSIONS: HIV-1 infected women bear significant burden of HPV infection and related disease. Prevention and screening programmes should be specifically deployed for this population in Ghana.

Review of errors in the issue of medical certificates of cause of death in a tertiary hospital in Ghana.

OBJECTIVE: Reliable mortality statistics are useful in determining national policies on preventive and interventional medicine. This study reviews, completed medical certificates of cause of death at the Cape Coast Teaching Hospital, in order to determine their accuracy and reliability. METHODS: A one-year review of Medical Certificates of Cause of Death (MCCD) signed between 01-01-2013 and 31-12-2013 in the medical, pediatric, surgical and obstetrics/gynecology departments of Cape Coast Teaching Hospital were done, analyzing for errors using the WHO/ICD-10 guidelines as the standard. The errors were grouped into minor and major errors. RESULTS: In all, 337 medical certificates of cause of death were audited. Majority, 212(62.9%) were issued in the internal medicine and therapeutics department. 30.86% (104) MCCDs were completed by specialists while 69.14% (233) were completed by non-specialist medical officers. Over half (56.68%) of the MCCDs had major errors while all (100%) had at least one minor error. CONCLUSION: Our study showed significant errors in MCCD records, with the errors more likely in certificates issued by non-specialist medical officers. All the certificates audited had at least one minor error. Training of doctors on proper completion of MCCDs is strongly advocated. FUNDING: None of the authors received any financial support for this study.

Diagnosing and treating rare lesions in a low resource setting: lessons from ahybrid epithelioid trophoblastic tumor and choriocarcinoma.

OBJECTIVE: To raise awareness of the existence of a rare type of malignant trophoblastic tumor and discuss the diagnostic challenges and management of this lesion in a low resource setting. CASE REPORT AND INTERVENTION: A 35 -year -old G6P3 woman was referred to our facility on account of persistent vaginal bleeding due to a suspected incomplete miscarriage with a cervical mass. Her serum ß-HCG was elevated (36,900 mIU/ml) and examination showed a bleeding cervical mass. An initial histopathological diagnosis of moderately differentiated squamous cell carcinoma was reviewed to epithelioid trophoblastic tumor resulting in an extra-fascial hysterectomy. A final histopathological diagnosis of hybrid Epithelioid Trophoblastic Tumor and Choriocarcinoma (ETT/CC) was made after external review and immunohistochemistry. She received subsequent chemotherapy. CONCLUSION: Epithelioid trophoblastic tumor and its hybrids are difficult to diagnose. They may be diagnosed as moderately differentiated squamous cell carcinoma especially in low resource settings where cervical squamous cell carcinoma is relatively more common. A high index of suspicion, a serum ß HCG test and close collaboration between clinicians and pathologists can help make the diagnosis. FUNDING: None.

Ovarian Tumors in Children and Adolescents: A 10-Yr Histopathologic Review in Korle-Bu Teaching Hospital, Ghana.

To determine the histopathologic types, frequency of occurrence, age distribution, presenting signs, and symptoms of ovarian tumors in children and adolescents diagnosed at the Korle-Bu Teaching Hospital all histopathology slides and request cards of ovarian tumors diagnosed in subjects aged, 0 to 19 yr over a 10-yr period (2001-2010) were reviewed. Biographical and clinical data of the patients were collected. The results were entered into Epi-info to determine the frequency of various ovarian tumors in different age groups and their association with presenting signs and symptoms. A total of 67 (9.5%) ovarian tumors were diagnosed in patients aged 0 to 19 yr of a total of 706 diagnosed in all age groups during the period. The majority [44 (65.7%)] were germ cell tumors, the commonest being mature cystic teratoma. Burkitt lymphoma was the single most common malignant tumor, comprising 6(9%) of all the tumors, although as a group malignant germ cell tumors were still the most common malignant ovarian tumors in children and adolescents. Although germ cell tumors were the most common tumors in this age group (both benign and malignant), Burkitt lymphoma, a peculiar malignant tumor in this subregion, was the single most common malignant tumor of the ovary.

Ovarian Cancer in Ghana, a 10 Year Histopathological Review of Cases at Korle Bu Teaching Hospital.

To determine the histopathological types, age distribution, presenting signs and symptoms of ovarian cancers diagnosed at the Korle-Bu Teaching Hospital, Ghana. All histopathology slides and request cards of ovarian cancers diagnosed over a ten-year period (2001 to 2010) were reviewed and the cancers classified according to the World Health Organization 1999 classification. Biographical and clinical data of the patients were collected and results entered into Epi-info to determine the frequency, age distribution and clinical presentation of the various types of ovarian cancer. There were 192 (27.2%) ovarian cancers out of 706 ovarian tumours. Epithelial cancers were the most common: 100 (52.1%), followed by sex cord stromal cancers 66 (34.4%). Majority of epithelial cancers were serous adenocarcinomas (71/100) while most sex cord stromal cancers were adult granulosa cell tumours 46 (69.7%). The mean age of patients with adenocarcinoma was 49 years while that of the 46 adult granulosa cell tumours was 46.5 years. Patients present with varying combinations of symptoms and signs and ovarian cancers present at an earlier age compared to other populations, with the age of presentation being slightly lower for sex cord stromal cancers compared to adenocarcinomas. There are no specific symptoms or signs associated with ovarian cancer at presentation, to assist with diagnosis.