Performance of careHPV, hybrid capture 2 and visual inspection with acetic acid for detection of high-grade cervical lesion in Tanzania A cross-sectional study

Katanga, Johnson; Kjaer, Susanne K.; Manongi, Rachel; Wu, Chun Sen; Iftner, Thomas; Waldstrom, Marianne; Pembe, Andrea B.; Mwaiselage, Julius; Rasch, Vibeke
Publication year: 


Cervical cancer is the fourth most common cancer among women in the world and the second most common in low income countries (LICs) [1]. In 2012, it was estimated that 580,000 new cases were diagnosed globally, of which 85% were from LICs [1,2]. With an annual incidence rate of 34.8 per 100.000 women and a mortality rate of 22 per 100.000 women, sub-Saharan Africa is the region with the highest burden of cervical cancer [3]. The corresponding figures for North America are 7.5 per 100,000 being diagnosed and 2.3 per 100.000 dying from the disease [4]. Cervical high-grade lesions and cervical cancer are caused by persistent infection with human papillomavirus (HPV). It has been shown that immunocompromised individuals who are positive to human immunodeficiency virus (HIV), have an increased risk of HPV infection [5]. Furthermore, a higher HPV prevalence has been documented in women with decreasing CD4 count [6]. Finally, studies have shown that HIV positive women are at increased risk of cervical cancer. Cervical cancer is preventable, and curable if detected at an early stages. In high income countries (HICs), screening against cervical cancer using cervical cytology has reduced the incidence of cervical cancer with more than 50% during the past 40 years [7]. In contrast, there has been observed no decline or only little decline in LICs [8]. Moreover in sub-Saharan Africa, it appears as the incidence has increased during the past years [9,10]. The high incidence of cervical cancer in sub Saharan Africa reflects a low coverage of cervical cancer screening as well as high prevalence of HPV and HIV [11]. Visual inspection with acetic acid (VIA) is used as a primary screening test in many LICs since it is cheap and easily accessible. One of the drawbacks of VIA is the subjectivity of the diagnosis. This is reflected in, a meta-analysis that reported a sensitivity range between 41% and 92% for the detection of high-grade cervical lesions [12]. In an increasing number of HICs, HPV DNA testing is used as the primary screening method followed by e.g. cytology as a triage test. HPV DNA testing has good sensitivity but the specificity is not as optimal due to the occurrence and detection of transient infections with no concomitant cervical lesions.


Materials and method Enrolment and data collection

This study is a part of the CONCEPT project (Comprehensive prevention of cervical cancer in Tanzania), which is based on a collaboration between Ocean Road Cancer Institute (ORCI), Kilimanjaro Christian Medical Centre (KCMC), the Danish Cancer Society Research Center (DCS) and Southern University of Denmark (SDU). Women were enrolled from the cervical cancer screening clinics at ORCI, KCMC and Kilimanjaro Regional Hospital (Mawenzi) in Tanzania. ORCI is the national designated institute for cancer care and treatment in Tanzania. It is located in Dar es Salaam region which has a population of 4,364,541 inhabitants based on National census data for 2012 [17]. KCMC and Mawenzi hospital are situated in Kilimanjaro region, which has a population of 1,640,087 according to the 2012 census report [17]. Both hospitals serve as referral hospitals for people living in the northern zone of Tanzania. Women aged 25–60 years who attended routine cervical cancer screening were eligible for the study. Exclusion criteria were being pregnant, previous history of cervical precancerous lesion, known allergy to acetic acid and having menstrual period. We aimed at including at least 500 HIV positive women. The enrolment was done from August 2015 to November 2017 and eligible women underwent face-to-face interview to obtain information on socio-demographic and lifestyle factors followed by voluntarily HIV testing. They were then directed to a special designated room for gynaecologic examination and cervical sample collection. First, a cervical swab for careHPV was taken followed by a swab for LBC and HC2. Subsequently, VIA was performed as routine per Tanzania cervical cancer screening guideline



In more than 3600 women from a Sub-Saharan country (Tanzania), we evaluated test performance of careHPV, HC2 and VIA to detect cervical high-grade lesions with expert reviewed liquid-based cytology as the gold standard. Compared to HC2, careHPV had an only slightly lower sensitivity. In contrast, the test performance of VIA was poor. When using VIA as a triage test among careHPV positive women, the sensitivity decreased even further, whereas the specificity increased substantially. Screening is an essential component in the prevention of cervical cancer, however, in LICs conventional screening approaches are hampered by complex infrastructure and lack of expert staff. The World Health Organization therefore advocates a policy of ’screen and treat’ for cervical screening in LICs. This involves VIA followed by cervical cryotherapy or LEEP if indicated. The performance of VIA as a primary screening tool for the detection of cervical precancer and cancer has, however, shown rather inconsistent results. It is therefore increasingly being questioned whether VIA can stand alone as a scaled up screening procedure due to its high inter-operator variability and low sensitivity [22], and it has been suggested that HPV testing can be provided at point of care in LICs.