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Page 3 of 8  Original Research


              variables. We assessed all potential risk factors in univariate   Of the 80 women with a positive hrHPV test, 6 (7.5%) had a
              and multivariable  logistic regression models to determine   concurrent VIA positive result. Of these women, two were
              independent associations. Our final logistic regression model   positive  for  HPV  type  16  only,  one  for  HPV  16 and  other
              did not include VIA data as HPV infection is known to   types (channel 5) and three tested positive for other hrHPV
              precede VIA status. Incidence rates (IR) and IR ratios for   types (2 were channel 3 positive and the other had missing
              cervical disease defined as VIA positivity, high-grade   channel data).
              squamous intraepithelial neoplasia (HGSIL) and cervical
              cancer were assessed with the follow-up data. All statistical   In the univariate analysis shown in Table 2, women aged
              tests were two-tailed with  p < 0.05 considered significant   22–29 years (OR 3.0, 95% CI: 1.2–7.9, p = 0.02), women with
              and  95% confidence intervals [CI] used. In summary, our   a positive VIA within 2  years prior  to HPV screening
              descriptive, univariate and multivariate analysis were based   (OR 6.1, 95% CI: 2.9–12.8, p < 0.001), women on second-line
              on all data 100% (n = 321). Follow-up data was based on 96%   ART (OR 2.38, 95% CI: 1.3–4.4) and those with a positive
              (n = 308) women with hrHPV test results and without   VIA at time of HPV screen (OR 6.6, 95% CI: 1.6–27.6,
              incident cervical disease.                            p  <  0.001)  were  more  likely  to  test  positive  for  hrHPV.
                                                                    Having a detectable viral load at the time of screening and
              Ethical consideration                                 sexual debut between the age of 13 and 16 years were also
                                                                    significantly associated with hrHPV positivity (OR: 2.3, 95%
              The study was approved by the Newlands Clinic Research   CI: 1.01–5.3, p = 0.04, OR:3.2, CI: 1.3–7.9, p < 0.01). However,
              team and the Medical Research Council of Zimbabwe     no statistical significance for hrHPV positivity was observed
              (Approval MRCZ/A/1980).                               for CD4 count < 200 cells/mm (OR 1.2, CI: 0.4–4.0). In the
                                                                                             3
                                                                    multivariate analysis, only younger age (22–29 years),
              Results                                               (adjusted odds ratio [aOR] 2.9; 95% CI: 1.0–8.8, p = 0.05),
                                                                    ART regimen (aOR 2.1; 95% CI: 1.1–4.0, p < 0.05) and early
              We recruited 321 women with a median age of 44 years (IQR:
              38–50). One hundred and thirty-eight (43.0%) women were   sexual debut at ages 13–16 years (aOR 4.0, 95% CI: 1.4–11.5,
                                                                    p  <  0.05) showed  evidence  of  association  with  hrHPV
              married and 29.6% (n = 95) were widowed. Two-thirds of the   positivity (Table 2).
              women (63.9%, n = 205) were educated to high-school level
              (at least 8 years of formal education). Most women (64.5%,   Visual inspection with acetic acid follow-up
              n = 207) reported sexual debut between 17 and 21 years, and   outcomes after high-risk human papillomavirus
              13.4% (n = 43) were 16 years or below at sexual debut.   testing
              Regarding duration on ART, 233 (70.8%) had been on ART for
              more than 5 years (median ART duration = 7.8 years, IQR:   Three hundred and eight (96%) participants with negative
              4.4–10.8 years). In total, 252 (78.5%) were on a first-line ART   VIA at the time of hrHPV screen were followed up for a
              regimen (1 Non-nucleoside Reverse Transcriptase Inhibitor   median of 2 years (645 total  person-years of follow-up).
              [NNRTI] + 2 Nucleoside/Nucleotide Reverse Transcriptase   Follow-up was made to determine incident VIA positivity,
              Inhibitor [NRTI]) and had a median CD4 count of 525 cells/  incident HGSIL and incident cervical cancer (confirmed by
                 3
                                      3
              mm  (IQR 366–687 cells/mm . One-third (33.7%,  n = 108)   LEEP biopsy) by HPV infection status at baseline. The VIA
              reported that they were unaware of their partner’s HIV status   positivity IR in hrHPV-negative women was 0.79 per 100
              and 15.6% (n = 50) were in HIV sero-discordant relationships.   person-years (95% CI: 0.30–2.11). In hrHPV-positive women,
                                                                    the VIA positivity IR was 9.97 per 100 person-years (95% CI:
              Amongst the 310 women who had HIV viral load results,   5.90–16.83).  Incident  rate  ratio  between  the  two  groups  of
              91.2% (n = 283) had undetectable viral loads (below 50   women was 12.57 (95% CI: 4.14–38.19). There was no evidence
              copies/mL)  and  2.9%  (n  =  9)  had  a  viral  load  above  1000   of incident cervical disease (HGSIL) in women who tested
              copies/mL (Table 1).
                                                                    negative for hrHPV infection. Amongst women with hrHPV
                                                                    infection, the IR of HGSIL was 6.41 per 100 person-years
              All the 321 women had a successful HPV test, 80 (24.9%; 95%   (95% CI: 3.33–12.32). During the follow-up period, there was
              CI:  20.2%  – 29.7%)  were positive  for  any  hrHPV.  Human   no incident of cervical cancer regardless of hrHPV infection
              papillomavirus 16 positivity without other coinfections was   status (Figure 2).
              in 9 (11.2%) women, 10 (12.5%) were positive for HPV 18/45
              alone, 52 (65%) for other hrHPV. A small proportion, four (5%)   Of the 14 incident VIA-positive women at follow-up, eight
              had HPV 16 and other hrHPV coinfections, and five (6.3%)   (57%) at baseline were positive for other hrHPV subtypes
              had HPV 18 and other hrHPV. There were no co-infections   (four  being  channel  3  subtypes  and  the  others  having
              with HPV 16 and HPV 18/45. Data for specific channels   missing channel data), two were positive for HPV16, one
              positive for other hrHPV-positive samples were available for   was positive for HPV 16 and other hrHPV subtypes (channel
              56/61 samples (91.8%). Amongst these 56 samples, 40 (71.4%)   5).  Two  were  positive  for  hrHPV  18/45  only  and  one  for
              were positive in channel 3 (HPV31/33/35/52/58), 5 (7.1%) in   hrHPV 18/45 and other (channel 3). None of the women had
              channel 4 (HPV51/59) and 15 (26.8%) in channel 5 (HPV   16/18/45 coinfections at baseline. None of the women with
              39/56/66/68). One was positive in both channels 3 and 4,   positive channel 4 subtypes had incident cervical disease at
              whilst two were positive in both channels 3 and 5 (Figure 1).   follow-up.

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