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Page 2 of 8  Original Research


              high risk for precancerous and cancerous lesions. 10,11  This   management depending on the type and extent of the cervical
              modality of screening has not been rolled out in the region   lesion. Visual inspection with acetic acid and cryotherapy are
              because of the prohibitive cost of the test. The diagnostic   conducted by the nurses. The LEEP procedure is performed
              landscape is changing, and as cost-effective  point-of-care   by  a  gynaecologist,  and  the  excised  tissue  is  sent  to  an
              HPV DNA tests are becoming more accessible, countries   external laboratory for histological examination.
              have  commenced  HPV  screening  as  the  preferred  primary
              cervical cancer screening method. 12,13
                                                                    Study procedure
              The  Zimbabwean  government  partnering  with  GAVI,  the   We invited women attending cervical cancer screening
              Vaccine  Alliance in 2018, rolled out a national HPV   between 01 September 2017 and 21 November 2018 to
              vaccination programme, as its cervical cancer primary   participate in the study. Sexually active, HIV-positive
              prevention method. The programme targeted the countries’   women  above the  age of  18  years who  consented  to
              800 000 girls aged 10–14 using the bivalent vaccine, which   participate in the study were recruited. Potential participants
                                                        14
              confers  protection  to  hrHPV  subtypes  16/18/45.   This,   with a positive pregnancy test were excluded. Baseline
              however, has raised questions on the cross protective effect of   information including sexual history and demographic
              other hrHPV subtypes, which have been reported to be   information were collected and stored in a Microsoft Access
              prevalent amongst women in Zimbabwe. 15,16            database.

              Sub-Saharan African studies investigating HPV prevalence   At the baseline visit, we screened participants using VIA, the
              in WLHIV have shown a wide variability across different   study nurses collected endocervical swabs for the HPV DNA
              countries from 24% to 64%. 17,18,19,20,21,22  In 2017, a Zimbabwean   tests. Women who screened positive by VIA were reviewed
              study showed a hrHPV prevalence of 33% in a rural cohort   six monthly, and those who screened negative, annually.
              of 123 WLHIV. Types 35, 52 and 58 were found to be    For  the HPV DNA tests, we collected endocervical swabs
              amongst the highly prevalent types, in addition to types 16   using the Cervexbrush25 and deposited the samples into
              and 18.  These geographical differences in HPV burden   Preservcyt50 transport medium. We used Xpert® HPV kits
                    15
              and type distribution highlight the need to assess the   for testing on the GeneXpert machine located at the onsite
              Zimbabwean urban context independently. In this cohort   NC  laboratory.  The  test  detected  14  high-risk  HPV  with
              study, we investigated the prevalence of hrHPV, the   callouts for HPV 16, HPV 18/45 and ‘other hrHPV’. Amongst
              associated risk factors and VIA outcomes during 2 years of   the ‘other hrHPV’ subtypes are HPV 31, 33, 35, 39, 51, 52, 56,
              follow-up.
                                                                    58,  59,  66  and  68.  The  14  HPV  types  are  detected  in  five
              Methods                                               fluorescent channels, each with individual parameters for
                                                                    target detection and validity; channel 1: HPV16, channel 2:
              Study design and setting                              HPV18/45, channel 3: HPV31/33/35/52/58, channel 4:
              This analytic cohort study was conducted amongst WLHIV at   HPV51/59, channel 5: HPV 39/56/66/68. For channels in
                                                                                                           ®
              Newlands Clinic (NC), in Harare, Zimbabwe. The NC was   which more than one type is detected, the Xpert  HPV test
                                                                                                24
              established in 2004 in partnership with the Ministry of Health   does not distinguish between types.  Positive hrHPV results
              and Child Care (MoHCC) and provides comprehensive HIV   during the study period did not alter VIA follow-up intervals
              care to approximately 6500 men, women and children.  Sexual   which were determined by VIA results only. We followed up
                                                       23
              reproductive health services form an integral component of   participants with VIA screening for a median of 26 months
              HIV  care  at  NC  and  include  cervical  cancer  screening,   (interquartile range [IQR]: 24–28), which was up to  April
              diagnosis and treatment of sexually transmitted infections   2020. Participants with incident HPV-related disease as high-
              (STIs), and the provision of short- and long-acting reversible   grade vulva intraepithelial neoplasia (VIN3) were censored
              contraceptive methods. An HPV vaccination programme was   from further follow-up.
              also introduced at the clinic in 2015. In this year alone, 517
              adolescents and youth 12–22 years old (312 females and 205   We collected additional patient data including antiretroviral
              males) were vaccinated using the quadrivalent HPV vaccine.   therapy (ART) medication history, VIA screening results and
              The vaccination of children, adolescents and young adults still   laboratory results from the clinic’s electronic database. None
              continues to date at the clinic as part of the clinic’s effort to   of the women in the study cohort had an HPV vaccination
              prevent a potential burden of HPV-related cancers in these   history.
              young people as they mature.
                                                                    Statistical analysis
              Women registered in care at NC attend routine annual
              cervical cancer screening where the VIA method is used   We used Stata 13.1 (College Station, Texas) for data cleaning
              as  guided by the Zimbabwean Ministry of Health. The   and analysis. We used proportions and medians for
              procedure is performed by a team of three nurses who have   descriptive  statistics,  logistic  regression  and  the  associated
              been trained  in this technique.  Women  with a positive   Wald test for measures of association between hrHPV
              VIA  screen are treated with either cryotherapy, loop   test  and potential risk factors, and Wilcoxon Rank-Sum
              electrical excision procedure (LEEP) or referred for specialist   (Mann  Whitney) test differences between continuous

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