Cervical cancer therapies: Current challenges and future perspectives

Cervical cancer is the fourth most common female cancer worldwide and results in over 300 000 deaths globally. The causative agent of cervical cancer is persistent infection with high-risk subtypes of the human papillomavirus and the E5, E6 and E7 viral oncoproteins cooperate with host factors to induce and maintain the malignant phenotype. Cervical cancer is a largely preventable disease and early-stage detection is associated with significantly improved survival rates. Indeed, in high-income countries with established vaccination and screening programs it is a rare disease. However, the disease is a killer for women in low- and middle-income countries who, due to limited resources, often present with advanced and untreatable disease. Treatment options include surgical interventions, chemotherapy and/or radiotherapy either alone or in combination. This review describes the initiation and progression of cervical cancer and discusses in depth the advantages and challenges faced by current cervical cancer therapies, followed by a discussion of promising and efficacious new therapies to treat cervical cancer including immunotherapies, targeted therapies, combination therapies, and genetic treatment approaches.

Hyperthermia: A Potential Game-Changer in the Management of Cancers in Low-Middle-Income Group Countries

Loco-regional hyperthermia at 40–44 °C is a multifaceted therapeutic modality with the distinct triple advantage of being a potent radiosensitizer, a chemosensitizer and an immunomodulator. Risk difference estimates from pairwise meta-analysis have shown that the local tumour control could be improved by 22.3% (p < 0.001), 22.1% (p < 0.001) and 25.5% (p < 0.001) in recurrent breast cancers, locally advanced cervix cancer (LACC) and locally advanced head and neck cancers, respectively by adding hyperthermia to radiotherapy over radiotherapy alone. Furthermore, thermochemoradiotherapy in LACC have shown to reduce the local failure rates by 10.1% (p = 0.03) and decrease deaths by 5.6% (95% CI: 0.6–11.8%) over chemoradiotherapy alone. As around one-third of the cancer cases in low-middle-income group countries belong to breast, cervix and head and neck regions, hyperthermia could be a potential game-changer and expected to augment the clinical outcomes of these patients in conjunction with radiotherapy and/or chemotherapy. Further, hyperthermia could also be a cost-effective therapeutic modality as the capital costs for setting up a hyperthermia facility is relatively low. Thus, the positive outcomes evident from various phase III randomized trials and meta-analysis with thermoradiotherapy or thermochemoradiotherapy justifies the integration of hyperthermia in the therapeutic armamentarium of clinical management of cancer, especially in low-middle-income group countries

Knowledge, awareness, attitudes and screening practices towards breast and cervical cancer among women in Nepal: a scoping review

Aim
Breast and cervical cancers have emerged as major global health challenges and disproportionately affect women in low- and middle-income countries, including Nepal. This scoping review aimed to map the knowledge, attitudes and screening practices for these cancers among Nepali women to improve cancer outcomes and reduce inequality.

Methods
Five electronic databases (CINAHL, Embase, Global Health, PsycINFO and PubMed), grey literature, and reference and citation lists were searched for articles published in English up to June 2021. Articles were screened against inclusion/exclusion criteria, and data from eligible studies were extracted. Results were summarised narratively.

Results
The search yielded 615 articles, 38 of which were included in this scoping review (27 cervical cancer, 10 breast cancer, 1 both cancers). Levels of knowledge regarding breast and cervical varied widely. The main knowledge gaps were misconceptions about symptoms and risk factors, and poor understanding of screening behaviours. Screening practices were mostly inadequate due to socio-cultural, geographical or financial barriers. Positive attitudes towards cervical screening were associated with higher education and increased knowledge of screening modalities. Higher levels of knowledge, (health) literacy and participation in awareness campaigns facilitated breast cancer screening.

Conclusion
Knowledge and screening practices for breast and cervical cancer among Nepali women were poor and highlight the need for awareness and education programmes. Future research should explore community health worker-led awareness and screening interventions for cervical cancer, and programmes to increase the practice of breast self-examination and clinical breast examinations to support early diagnosis of breast cancer.

Knowledge of Palestinian women about cervical cancer warning signs: a national cross- sectional study

Background
Timely presentation and diagnosis of cervical cancer (CC) are crucial to decrease its mortality especially in low- and middle-income countries like Palestine. This study aimed to evaluate the knowledge of Palestinian women about CC warning signs and determine the factors associated with good knowledge.

Methods
This was a national cross-sectional study conducted between July 2019 and March 2020 in Palestine. Stratified convenience sampling was used to recruit adult women from hospitals, primary healthcare centers, and public spaces of 11 governorates. A translated-into-Arabic version of the validated CC awareness measure (CeCAM) was used to assess women’s knowledge of 12 CC warning signs.

Results
Of 8086 approached, 7223 participants completed the CeCAM (response rate = 89.3%). A total of 7058 questionnaires were included in the analysis: 2655 from the Gaza Strip and 4403 from the West Bank and Jerusalem (WBJ). The median age [interquartile range] for all participants was 34.0 [24.0, 42.0] years. Participants recruited from the WBJ were older, getting higher monthly income, and having more chronic diseases than those recruited from the Gaza Strip.

The most frequently identified warning sign was ‘vaginal bleeding after menopause’ (n = 5028, 71.2%) followed by ‘extreme generalized fatigue’ (n = 4601, 65.2%) and ‘unexplained weight loss’ (n = 4578, 64.9%). Only 1934 participants (27.4%) demonstrated good knowledge of CC warning signs. Participants from the Gaza Strip were slightly more likely than participants from the WBJ to have a good level of knowledge. Factors associated with having good knowledge included having a bachelor or postgraduate degree, being married, divorced, or widowed as well as knowing someone with cancer.

Conclusion
The overall awareness of CC warning signs was low. Educational interventions are needed to increase Palestinian women’s awareness of CC warning signs.

Essential Package of Palliative Care for Women With Cervical Cancer: Responding to the Suffering of a Highly Vulnerable Population

Women with cervical cancer, especially those with advanced disease, appear to experience suffering that is more prevalent, complex, and severe than that caused by other cancers and serious illnesses, and approximately 85% live in low- and middle-income countries where palliative care is rarely accessible. To respond to the highly prevalent and extreme suffering in this vulnerable population, we convened a group of experienced experts in all aspects of care for women with cervical cancer, and from countries of all income levels, to create an essential package of palliative care for cervical cancer (EPPCCC). The EPPCCC consists of a set of interventions, medicines, simple equipment, social supports, and human resources, and is designed to be safe and effective for preventing and relieving all types of suffering associated with cervical cancer. It includes only inexpensive and readily available medicines and equipment, and its use requires only basic training. Thus, the EPPCCC can and should be made accessible everywhere, including for the rural poor. We provide guidance for integrating the EPPCCC into gynecologic and oncologic care at all levels of health care systems, and into primary care, in countries of all income levels.

Augmented Package of Palliative Care for Women With Cervical Cancer: Responding to Refractory Suffering

The essential package of palliative care for cervical cancer (EPPCCC), described elsewhere, is designed to be safe and effective for preventing and relieving most suffering associated with cervical cancer and universally accessible. However, it appears that women with cervical cancer, more frequently than patients with other cancers, experience various types of suffering that are refractory to basic palliative care such as what can be provided with the EPPCCC. In particular, relief of refractory pain, vomiting because of bowel obstruction, bleeding, and psychosocial suffering may require additional expertise, medicines, or equipment. Therefore, we convened a group of experienced experts in all aspects of care for women with cervical cancer, and from countries of all income levels, to create an augmented package of palliative care for cervical cancer with which even suffering refractory to the EPPCCC often can be relieved. The package consists of medicines, radiotherapy, surgical procedures, and psycho-oncologic therapies that require advanced or specialized training. Each item in this package should be made accessible whenever the necessary resources and expertise are available.

Dataset evaluating the treatment timeliness of cervical cancer in Zambia

Cervical cancer is the fourth most common cancer diagnosed among women globally. Effective screening routines and early detection are vital in reducing its disease burden and mortality. Several factors can influence the timely detection and treatment of cervical cancer, especially in low middle-income countries where the burden of this disease is highest. The data presented in this paper relates to the research article “Cervical cancer diagnosis and treatment delays in the developing world: Evidence from a hospital-based study in Zambia”. The raw and analysed data include the studied patients’ social demographic factors, clinical data concerning the stage and histological subtype of cancer, dates at which the various activities within the cancer treatment pathway occurred and delays to definitive treatment of cervical cancer at Zambia’s only cancer treatment facility. Detailing delays to the treatment of cervical cancer allows recognition of specific points in the cancer treatment pathway requiring intervention to effectively improve cancer care and reduce the morbidity and mortality associated with the disease.

Assessing service availability and readiness to manage cervical cancer in Bangladesh

Background
The second most common cancer among females in Bangladesh is cervical cancer. The national strategy for cervical cancer needs monitoring to ensure that patients have access to care. In order to provide accurate information to policymakers in Bangladesh and other low and middle income countries, it is vital to assess current service availability and readiness to manage cervical cancer at health facilities in Bangladesh.

Methods
An interviewer-administered questionnaire adapted from the World Health Organization Service Availability and Readiness Assessment Standard Tool was used to collect cross-sectional data from health administrators of 323 health facilities in Bangladesh. Services provided were categorized into domains and service readiness was determined by mean readiness index (RI) scores. Data analysis was conducted using STATA version 13.

Results
There were seven tertiary and specialized hospitals, 118 secondary level health facilities, 124 primary level health facilities, and 74 NGO/private hospitals included in the study. Twenty-six per cent of the health facilities provided services to cancer patients. Among the 34 tracer items used to assess cancer management capacity of health facilities, four cervical cancer-specific tracer items were used to determine service readiness for cervical cancer. On average, tertiary and specialized hospitals surpassed the readiness index cutoff of 70% with adequate staff and training (100%), equipment (100%), and diagnostic facilities (85.7%), indicating that they were ready to manage cervical cancer. The mean RI scores for the rest of the health facilities were below the cutoff value, meaning that they were not prepared to provide adequate cervical cancer services.

Conclusion
The health facilities in Bangladesh (except for some tertiary hospitals) lack readiness in cervical cancer management in terms of guidelines on diagnosis and treatment, training of staff, and shortage of equipment. Given that cervical cancer accounts for more than one-fourth of all female cancers in Bangladesh, management of cervical cancer needs to be available at all levels of health facilities, with primary level facilities focusing on early diagnosis. It is recommended that appropriate standard operating procedures on cervical cancer be developed for each level of health facilities to contribute towards attaining sustainable developmental goals.

Digital Health Strategies for Cervical Cancer Control in Low- and Middle-Income Countries: Systematic Review of Current Implementations and Gaps in Research

Background:
Nearly 90% of deaths due to cervical cancer occur in low- and middle-income countries (LMICs). In recent years, many digital health strategies have been implemented in LMICs to ameliorate patient-, provider-, and health system–level challenges in cervical cancer control. However, there are limited efforts to systematically review the effectiveness and current landscape of digital health strategies for cervical cancer control in LMICs.

Objective:
We aim to conduct a systematic review of digital health strategies for cervical cancer control in LMICs to assess their effectiveness, describe the range of strategies used, and summarize challenges in their implementation.

Methods:
A systematic search was conducted to identify publications describing digital health strategies for cervical cancer control in LMICs from 5 academic databases and Google Scholar. The review excluded digital strategies associated with improving vaccination coverage against human papillomavirus. Titles and abstracts were screened, and full texts were reviewed for eligibility. A structured data extraction template was used to summarize the information from the included studies. The risk of bias and data reporting guidelines for mobile health were assessed for each study. A meta-analysis of effectiveness was planned along with a narrative review of digital health strategies, implementation challenges, and opportunities for future research.

Results:
In the 27 included studies, interventions for cervical cancer control focused on secondary prevention (ie, screening and treatment of precancerous lesions) and digital health strategies to facilitate patient education, digital cervicography, health worker training, and data quality. Most of the included studies were conducted in sub-Saharan Africa, with fewer studies in other LMIC settings in Asia or South America. A low risk of bias was found in 2 studies, and a moderate risk of bias was found in 4 studies, while the remaining 21 studies had a high risk of bias. A meta-analysis of effectiveness was not conducted because of insufficient studies with robust study designs and matched outcomes or interventions.

Conclusions:
Current evidence on the effectiveness of digital health strategies for cervical cancer control is limited and, in most cases, is associated with a high risk of bias. Further studies are recommended to expand the investigation of digital health strategies for cervical cancer using robust study designs, explore other LMIC settings with a high burden of cervical cancer (eg, South America), and test a greater diversity of digital strategies.

Cervical cancer diagnosis and treatment delays in the developing world: Evidence from a hospital-based study in Zambia

Expedited diagnostic processes for all suspected cervical cancer cases remain essential in the effort to improve clinical outcomes of the disease. However, in some developing countries like Zambia, there is paucity of data that assesses factors influencing diagnostic and treatment turnaround time (TAT) and other metrics vital for quality cancer care. We conducted a retrospective hospital-based study at the Cancer Diseases Hospital (CDH) for cervical cancer cases presenting to the facility between January 2014 and December 2018. Descriptive statistics were used to summarize demographic characteristics while a generalized linear model of the negative binomial was used to assess determinants of overall TAT. Our study included 2121 patient case files. The median age was 49 years (IQR: ±17) and most patients (n=634, 31%) were aged between 41–50 years. The International Federation of Gynaecology and Obstetrics (FIGO) Cancer stage II (n =941, 48%) was the most prevalent while stage IV (n=103, 5.2%) was the least. The average diagnostic TAT in public laboratories was 1.48 (95%CI: 1.21–1.81) times longer than in private laboratories. Furthermore, referral delay was 55 days (IQR: 24–152) and the overall TAT (oTAT) was 110 days (IQR: 62–204). The age of the patient, HIV status, stage of cancer and histological subtype did not influence oTAT while marital status influenced oTAT. The observed longer oTAT may increase irreversible adverse health outcomes among cervical cancer patients. There is a need to improve cancer care in Zambia through improved health expenditure especially in public health facilities.