Multiple human papillomavirus infections and HIV seropositivity as risk factors for abnormal cervical cytology among female sex workers in Nairobi

Abstract

We estimated type-specific prevalence of human papillomavirus (HPV) and examined risk factors for abnormal cervical cytology among 296 female sex workers from Nairobi, Kenya. Over half (54%) were infected with a high-risk (HR) HPV type, of which HPV16 and 52 were the most common types. HIV-1 prevalence was 23% and HIV-1 sero-positivity was associated with high-grade cervical lesions, particularly among women with CD4 count less than 500 cells/mm³ (odds ratio [OR] = 6.9; 95% confidence interval [CI]: 1.7–24.9). Among women who had normal cytology at the time of entry into the study, the risk of having an abnormal Pap smear within one year was significantly elevated for women with multiple HPV types at study entry (adjusted odds ratio [aOR] = 6.0; 95% CI: 2.3–15.7) and with a subset of HR HPV types (aOR = 4.2; 95% CI: 1.6–11.2). Detection of multiple concurrent HPV infections may be a useful marker to identify women at risk of developing precancerous lesions in populations of high HPV prevalence.

Keywords

sexually transmitted infection human papillomavirus HPV HIV cervical dysplasia sex workers Africa

Introduction

Human papillomavirus (HPV) is the primary aetiological agent for invasive cervical cancer (ICC) and ranges in prevalence from 18% to 60% among women in Africa.¹ An annual mortality of 34.6/100,000 women makes ICC the leading cause of cancer-related mortality among women in sub-Saharan Africa.² The annual ICC incidence in Eastern Africa (34.5 cases per 100,000 women) is among the highest in the world.²

Female sex workers (FSWs) are at high risk for sexually transmitted infections (STIs), including HPV infection, given their relatively high weekly and lifetime number of sexual partners.^3,4 Only a few studies have examined HPV prevalence in FSWs in sub-Saharan Africa, and none of the studies provided follow-up cervical cytology results after initial laboratory-based HPV-positivity.^5–9 Despite previous data suggesting that other STIs are co-factors of HPV infection in increasing risk of cervical neoplasia and ICC,^10,11 few data are currently available from high sexual-risk populations in Africa.¹² Additionally, data have not been previously reported on the impact of multiple concurrent HPV infections on cervical dysplasia in FSWs who are at relatively high risk for exposure to many HPV types due to multiple partnerships.

We evaluated the prevalence of type-specific cervical HPV infection and demographic characteristics associated with abnormal cytology at study entry. We examined the impact of baseline HPV status on the development of abnormal cytology among women who were cytologically normal at study entry.

Subjects, Materials and Methods

Study population, enrolment and study visits

Peer leader recruitment efforts were used in the year 2000 to establish a cohort of 300 FSWs to investigate the immunogenesis of Chlamydia trachomatis infection in the Korogocho community, Nairobi, Kenya.¹³ In November 2003, an ancillary HPV study was nested within the existing cohort to form the basis of the current study. Eligibility criteria for enrolment in the HPV ancillary study included age 18–50 years, current enrollment in the existing C. trachomatis cohort and no history of hysterectomy. A total of 300 women consented to participate in the HPV study and attended the baseline clinic visit, at which time a pretested questionnaire on sociodemographic factors and sexual behaviour was administered by trained clinic staff. All participants who consented to enrol in the study were scheduled to follow-up visits at six-month intervals over the 12-month study period. The study was approved by the Institutional Review Boards (IRB) at Kenyatta National Hospital (Nairobi, Kenya) and the University of North Carolina (Chapel Hill, NC, USA).

Clinical examination and specimen collection

At the time of entry into the study (baseline visit), consenting participants received HIV-1 pretest counselling and blood draws for HIV-enzyme-linked immunosorbent assay (ELISA) testing. A pelvic exam was performed and a cervical swab was taken to detect C. trachomatis and Neisseria gonorrhoeae infections. A cervical brush specimen was collected and placed into PreservCyt liquid media (Hologic, Bedford, MA, USA) for HPV DNA testing and liquid based cytology. A conventional Pap smear was also conducted by collection of cervical cells through standard methods using a brush and spatula. A sample from the upper lateral vaginal wall was taken by swab, spread on a glass slide and air-dried for evaluation of bacterial vaginosis.

The liquid-based cytological smear was repeated at each six-month follow-up visit. Liquid-based cytological diagnoses were classified according to the Bethesda classification system¹⁴ at the laboratories of the Harborview Medical Center at the University of Washington in Seattle.

Women with abnormal cytology results received further clinical care. When the abnormality was low-grade squamous intraepithelial lesion (LSIL) or abnormal squamous cells of undetermined significance (ASCUS), a Pap smear was repeated in six months. Women with high-grade cytology results or greater were referred to Kenyatta National Hospital (KNH) for colposcopy, biopsy and treatment if indicated. All women with cervical intraepithelial lesions (CIN) 2 or greater were treated with loop electrosurgical excision procedure (LEEP) or total hysterectomy at KNH; those with CIN1 were triaged to follow-up with a repeat Pap smear at six months. Histopathology of biopsy specimens was conducted by an expert pathologist at the University of Nairobi's Department of Pathology.

HPV DNA testing

HPV DNA detection by polymerase chain reaction (PCR) was performed on samples collected in PreservCyt media using LI consensus primers MY09/MY11/HMB01 followed by Roche Diagnostics line blot assay in Seattle.¹³ Specimen adequacy was confirmed using β-globin positivity according to the manufacturer's instructions (Roche Diagnostics, Basel, Swizerland). A total of 36 different HPV types were detected. HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 were considered high-risk (HR) HPV types. HPV 6, 11, 26, 40, 42, 53, 54, 55, 61, 62, 64, 67, 69, 70, 71, 72, 73, 81, 82, 83, 84 and cp6108 were considered low-risk HPV types.

Testing for HIV, Chlamydia, gonorrhoea and bacterial vaginosis

HIV serology was performed using a synthetic ELISA (Detect HIV-1, Biochem ImmunoSystems, Inc, Montreal, Canada) at University of Nairobi Institute of Tropical and Infectious Disease (UNITID). If the first serological test was positive, a second confirmatory HIV assay was performed (Recombigen, Cambridge Biotech LTD, Worcester, MA). HIV-1 seropositive women underwent CD4 cell count determination, and were referred for HIV care and treatment within the Kariobangi clinic. CD4 lymphocyte counts from blood samples were analysed by FACScan flow cytometry (Becton-Dickinson, Sunnyvale, CA, USA).¹⁵ CD4 counts greater than or equal to 500 cells/mm³ were considered normal and this cut-off point was used in analysis of CD4 count as a risk factor for high risk HPV and abnormal cytology. Genital N. gonorrhoeae and C. trachomatis infections were detected by DNA PCR testing (AMPLICOR, Roche Diagnostic Systems, Branchburg, NJ, USA) as previously described at UNITID.¹⁵

To test for bacterial vaginosis (BV), air-dried vaginal samples were transported to Femicare, Tienen, Belgium for phase contrast microscopy (Leica DM LS2, Warburg, Germany) at 400 times magnification after re-hydrating the smear with one droplet of saline. Microscopy was performed on all air dried fresh smears by an investigator (Donders) blinded of all other study results. Slides were scored according to previously described methods.¹⁶ BV was defined as the presence of Gardnerella vaginalis or Mobiluncus morphotypes and/or clue cells in combination with the absence of lactobacilli (lactobacil-lary grade III). This diagnosis can be reliably compared with a Nugent score ≥7 on Gram stain.¹⁷ For study purposes, partial BV and full BV were not distinguished.

Statistical analysis

HR-HPV type-specific distribution is presented by proportions graphically, in the total study population as well as in the group of women with abnormal cytology. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression to examine associations between baseline characteristics and HR and multiple HPV types among women with normal cytology to identify potential confounders. Logistic regression was also used to examine associations between baseline characteristics and abnormal cervical cytological results, adjusting for age and HIV status. Exact ORs and 95% CIs were calculated for strata with small sample sizes. This study examined cytological outcomes at the first follow-up visit that occurred between 6 and 12 months following the baseline visit, excluding women who had baseline high-grade lesions because they were referred for colposcopy and treatment after baseline cytology. Odds ratios were calculated to evaluate the risk of abnormal cytology within one year of follow-up by baseline HPV status adjusting for age and HIV status using logistic regression. Analyses were performed using STATA version 9.1 (College Station, TX, USA).

Results

Results at baseline visit

A total of 300 women were enrolled in the cohort. Of these women, 296 (99%) had a laboratory-satisfactory HPV DNA test result at the baseline visit and were included in analyses. The median age of participants was 23 years (range: 18–43 years). A total of 19 of 296 women (6%) were equal or older than 30 years. Women had been FSW for a median of 3 years (range: 0–18 years) and had a median of 10 sexual partners per week (range: 0–60 partners). The median age at first sexual intercourse was 16 years (range: 11–23 years). A total of 265 (89.5%) women had satisfactory cytology results at baseline: 187 women (63%) had normal cytology results, 62 (21%) had low-grade lesions (LSIL/ASCUS) and 16 (5%) had high-grade lesions (HSIL/ASC-H/ICC). Among the women with high-grade lesions, 3 (19%) women were under 21 years, 11 (69%) were between 22 and 29 years and 2 (13%) women were age 30 or older. The median age of the 16 women with high-grade lesions was 23.5 years (range: 18–35 years). Three to four years of sex work was significantly associated with having multiple HPV infections at baseline (Table 1), but not with cervical dysplasia (Table 2).

Table 1

Baseline characteristics and risk factors for high-risk HPV (HR HPV) infection and multiple HPV infections among 296 female sex workers

	Overall N = 296 (%HR HPV-positive)	HR HPV OR (95% CI)^∗	Multiple HPV types OR (95% CI)^∗
Age, years
≥23	155(55)	0.9(0.5–1.4)	0.6(0.4–1.1)
<23	141 (54)	1.0	1.0
HIV status
HIV-1-seropositive	68(79)	4.5 (2.3–8.6)	7.2(3.8–13.8)
HIV-1-seronegative^†	228 (47)	1.0	1.0
Chlamydia trachomatis ^†
PCR positive	16(44)	0.6 (0.2–2.0)^§	1.0(0.3–3.0)^§
PCR negative^†	277 (55)	1.0	1.0
Neiseria gonorrhoeae ^‡
PCR positive	8(50)	0.8 (0.2–4.6)^§	1.2 (0.2–6.8)^§
PCR negative^†	285 (54)	1.0	1.0
Bacterial vaginosis ^‡
Yes	79 (59)	1.2 (0.8–1.8)	1.1 (0.7–1.6)
No^†	187(53)	1.0	1.0
Education level ^‡
Secondary or more	53 (53)	0.9(0.5–1.8)	0.7(0.4–1.4)
Primary or less^†	242 (55)	1.0	1.0
Age at first sexual encounter, years ^‡
≤16	190(54)	0.9(0.5–1.4)	0.8(0.5–1.4)
>16^‡	101 (54)	1.0	1.0
Years of female sex work ^‡
>4	74 (61)	1.2 (0.9–1.8)	1.3(0.9–1.9)
3–4	136(54)	1.4(0.8–2.5)	2.0(1.1–3.8)
<3^†	84 (49)	1.0	1.0
Weekly number of sex partners
>11	133(53)	0.9(0.6–1.2)	1.0(0.7–1.4)
6–11	122 (55)	0.7(0.3–1.5)	1.2(0.5–2.5)
≤5^†	41 (59)	1.0	1.0
Live births ^‡
≥2	127(55)	1.0(0.6–1.6)	1.1 (0.6–1.9)
≤1^†	138(53)	1.0	1.0
Condom use ^‡
>99%	31 (45)	1.0(0.6–1.6)	1.0(0.6–1.6)
50–99%	184(59)	1.6(0.9–2.8)	1.2 (0.7–2.3)
<50%^†	77 (48)	1.0	1.0
Current oral contraception use
Yes	65 (48)	0.7(0.4–1.3)	0.7(0.4–1.3)
No^†	231 (56)	1.0	1.0
Current smoker ^‡
Yes	69 (57)	1.1 (0.7–2.0)	1.4(0.8–2.5)
No^†	226 (54)	1.0	1.0

Odds ratio (OR) estimates and confidence intervals (CIs) based on logistic regression

High-risk HPV types = 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68

∗

Adjusted for HIV serostatus and age <23 and ≥23 years

†

Reference

‡

Numbers do not add up to total sample size due to missing data

Exact OR CIs

Table 2

Risk factors for high- and low-grade cervical lesions among 265 female sex workers

	N (%) Normal cytology (N = 187)	OR (95% CI)^∗
	N (%) Normal cytology (N = 187)	LSIL/ASCUS (N = 62)	HSIL^† (N = 16)
Median age, years
≥23	95 (50.8)	1.0(0.6–1.8)	1.9(0.6–5.7)
<23	92 (49.2)	1.0	1.0
HIV-seropositive	32 (17.1)	2.1 (1.1–4.2)	3.8(1.1–12.2)^‡
CD4 count <500^§	15(8.0)	2.9(1.3–6.7)	6.9(1.7–24.9)^‡
CD4 count ≥500^§	16(8.6)	1.4(0.5–3.7)	1.1 (0.0–8.70)^‡
HIV-seronegative^∗∗	155(82.9)	1.0	1.0
High-risk HPV	92 (49.2)	1.6(0.9–3.0)	6.0(1.3–28.2)
High-risk HPV-negative^∗∗	95 (50.8)	1.0	1.0
HPV 16 or 18	18(9.6)	2.4(1.1–5.36)	10.2 (3.2–31.4)
HPV 16/18 negative^∗∗	169(90.4)	1.0	1.0
HPV 16, 18, 33 or 45	25(13.4)	2.6(1.3–5.2)	13.4(4.1–43.6)
HPV 16/18/33/45 negative^∗∗	162 (86.6)	1.0	1.0
HPV 16, 18, 33, 45, 52 or 58	50 (26.7)	1.7(0.9–3.2)	8.0 (2.3–28.5)
HPV 16/18/33/45/52/58 negative^∗∗	137(73.3)	1.0	1.0
Multiple-HPV types	68 (36.4)	2.2 (1.2–4.0)	11.9 (2.4–57.9)
≤1 HPV type^∗∗	119 (63.6)	1.0	1.0
Chlamydia trachomatis PCR-positive^§	8 (4.3)	0.7 (0.1–3.8)^‡	–
Gonorrhoea PCR-positive^§	4 (2.1)	1.5 (0.1–10.8)^‡	–
Bacterial vaginosis^§	46 (24.6)	1.5(0.8–2.9)	1.4(0.4–4.4)
Education level
Secondary or more	30 (16.0)	1.1 (0.5–2.3)	1.2 (0.3–4.6)
Primary or less^∗∗	156(83.4)	1.0	1.0
Age at first sexual encounter, years ^§
≤16	118(63.1)	1.8(0.9–3.7)	1.2 (0.4–3.9)
>16^∗∗	68 (36.4)	1.0	1.0
Years of female sex work ^§
>4	49 (26.2)	0.6(0.3–1.6)	2.7(0.5–14.5)
3–4	80 (42.8)	1.6(0.8–3.2)	2.8(0.5–14.6)
<3^∗∗	57 (30.5)	1.0	1.0
Weekly number of sex partners
>11	93 (49.7)	0.7(0.3–1.6)	0.9 (0.2–4.9)
6–11	69 (36.9)	1.1 (0.5–2.7)	1.1 (0.2–6.1)
≤5^∗∗	25(13.4)	1.0	1.0
Live births ^§
≥2	76 (40.6)	0.9(0.5–1.8)	1.5(0.5–4.6)
≤1^∗∗	85 (45.5)	1.0	1.0
Condom use ^§
>99%	20(10.7)	0.5(0.1–1.5)^‡	2.2 (0.27–17.7)^‡
50–99%	119(63.6)	0.8(0.4–1.5)	1.2 (0.3–7.3)^‡
<50%^∗∗	44 (23.5)	1.0	1.0
Current oral contraception use
Yes	40(21.4)	0.7(0.3–1.5)	1.2 (0.3–3.8)
No^∗∗	147(78.6)	1.0	1.0
Current smoker ^§
Yes	44 (23.5)	0.9(0.5–1.9)	1.1 (0.3–3.8)
No^∗∗	142 (75.9)	1.0	1.0

Odds ratio (OR) estimates and confidence intervals (CIs) based on logistic regression

Cases of low-grade or high-grade lesions on liquid based cytology were compared with subjects with normal liquid based cytology. High-risk HPVtypes=16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68

∗

Adjusted for HIV serostatus and age <23 and ≥23 years

†

High-grade squamous intraepithelial lesion (HSIL) includes one case of invasive cervical cancer (ICC) and three cases of abnormal squamous cells, cannot rule out high grade (ASC-H) by liquid based cytology

‡

Exact OR CIs

Numbers do not add up to total sample size due to missing data

∗∗

Referent

Overall, 195 (66%) of 296 FSWs were positive for cervical HPV infection at baseline. Among all 296 women, 54% had high-risk (HR) HPV and 44.3% had low-risk (LR) HPV. A total of 133 (45%) had more than one HPV type identified in their cervical samples and 82 (28%) had more than one HR HPV type infection. The five most common high-risk HPV types in this population were 16 and 52 (9.5% each), 35 and 58 (9% each) and 51 (8%). HPV 18 prevalence was 6% (Figure 1). The HR-HPV type most commonly associated with high-grade lesions was HPV 16 (37.5%), followed by HPV 18, 33, 45, 52 and 58, which were equally common (19%). HPV 53 (11.5%) and 54 (9.8%) were the most common LR-HPV types.

Figure 1

High-risk human papillomavirus (HPV) genotype distribution among 296 female sex workers in Nairobi, Kenya. Distribution of type specific high-risk (HR) HPV infection and abnormal cytology by HR type in the total study population (abnormal cytology includes high-grade squamous intraepithelial lesion [HSIL], low-grade squamous intraepithelial lesion, abnormal squamous cells of undetermined significance [ASCUS], abnormal squamous cells, cannot rule out high grade [ASC-H], and invasive cervical cancer [ICC]) by liquid-based cytology results

Sixty-eight (23%) women were HIV-1-seropositive, among whom 54 (79%) were co-infected with HR HPV infection as compared with 107 (47%) of HIV seronegative women (aOR = 4.5; 95% CI: 2.3–8.6). Among HIV-1-seropositive women, the most common HR HPV infections were HPV 52 (21%) and 16 (18%). Twenty-five (37%) HIV-1-seropositive women, as compared with 16% of HIV-1 uninfected women, were infected with at least one of the HPV types most commonly associated with ICC in Africa (HPV 16, 18, 33, 45).¹⁸ When HIV serostatus was stratified by CD4 count, the subset of HIV-1 positive women with CD4 counts less than 500 cells/mm had a higher prevalence of these HR types (aOR = 4.4; 95% CL2.2–9.1) in comparison to HIV-1 positive women with a CD4 count ≥500 cells/mm³ (aOR = 1.5; 95% CLO.6–3.9). HIV-1 seropositivity was also associated with a higher risk of multiple concurrent HPV infections (aOR = 7.2; 95% CI: 3.8–13.8).

The group of HPV types 16,18, 33 or 45, was associated with a higher risk of low-grade and high-grade cervical lesions (Table 2). Co-infection with multiple HPV types was also associated with abnormal cytology. HIV-1-seropositive women, particularly those with CD4 counts less than 500 cells/mm, were at significantly increased risk for both low-grade and high-grade cervical lesions as compared with HIV-1-negative women (Table 2).

Results from follow-up visit

A total of 119 FSWs with satisfactory baseline cytology and HPV DNA results had a satisfactory follow-up cervical cytology result 6–12 months after the baseline visit. Having any high-risk HPV infection at baseline was not significantly associated with having abnormal cytology at follow-up. Among 94 women with normal baseline cytology, baseline co-infection with multiple HPV types had the highest OR point estimate (OR = 6.0 95% CI: 2.3–15.7) for developing abnormal cytology within one year of follow-up (Table 3).

Table 3

Cumulative 12-month risk of abnormal cytology among 119 female sex workers from Kenya

HPV status	Baseline status among women with follow-up cytology within 12 months (N = 119)	Abnormal cytology at follow-up (N = 27)^∗		Incident lesion at follow-up in women with normal baseline cytology^† (N = 19)
HPV status		N (%)	RR (95% CI)^‡	N (%)	RR (95% CI)^‡
HIV seropositive
Yes	17	7(26)	2.9(1.0–8.6)	4(21)	2.6(0.7–10.3)
No^§	102	20 (74)	1.0	15(79)	1.0
HPV DNA
Yes	63	20 (74)	2.9(1.1–7.6)	13(68)	2.5 (0.8–7.5)
No^§	56	7(26)	1.0	6(32)	1.0
High-risk HPV^∗∗
Yes	51	17(63)	2.6(1.0–6.4)	11 (58)	2.1 (0.7–6.3)
No^§	68	10(37)	1.0	8(42)	1.0
HPV 16 or 18
Yes	9	3(11)	1.7 (0.4–7.4)	2(11)	1.6(0.3–9.5)
No^§	110	24 (89)	1.0	17(89)	1.0
HPV 16, 18, 33, or 45
Yes	16	7(26)	3.0(1.0–9.1)	3(16)	1.7 (0.4–7.7)
No^§	103	20 (74)	1.0	16(84)	1.0
HPV 16, 18, 33, 45, 52, or 58
Yes	28	13(48)	4.2 (1.6–11.2)	8(42)	3.5(1.0–12.0)
No^§	91	14(52)	1.0	11 (58)	1.0
Multiple HPV types
Yes	36	17(63)	6.0(2.3–15.7)	11 (58)	4.9(1.6–15.3)
No^§	83	10(37)	1.0	8(42)	1.0

Women with high-grade squamous intraepithelial lesion (HSIL) at baseline, unsatisfactory cytology at baseline or at follow-up were excluded from analyses

∗

Control group was anyone who had normal cytology at follow-up. This includes women with low-grade squamous intraepithelial lesions/abnormal squamous cells of undetermined significance (LSIL/ASCUS) that regressed (n = 17) as well as women with persistently normal cytology (n = 75)

†

Normals→LSI L/ ASCUS, or Normal→HSIL. The control group was women with normal baseline and follow-up cytology (n = 75)

‡

Odds ratio (OR) and 95% confidence intervals (CI) based on logistic regression adjusted for age (<23 or ≥23) and HIV serostatus

Reference

∗∗

High risk (HR) HPV types: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68

Discussion

This study contributes to the limited knowledge of HPV infection and cervical neoplasia in sex workers in Africa, and represents the only study in this sub-population that includes follow-up cytology results. Worldwide literature shows that young women have a relatively high prevalence of HPV infection, although most HPV infections resolve spontaneously over time without any intervention.¹⁹ More than half (57.4%) of this cohort was less than 24 years of age; therefore, the results may not be generalizable to other age ranges in the general Kenyan population. We do not present follow-up data on genital HPV infection, which is part of ongoing analyses. Further, our analyses are limited to cytological, rather than histological endpoints. We believe, however that our results are relevant given that clinical practice is dependent upon cytological outcomes. Other study limitations include the relatively low prevalence of STIs and relative low precision in evaluating potential risk factors for HPV infection and abnormal cervical cytology, particularly in specific strata (HIV-1-seropositive women with low CD4 counts) due to our relatively small sample sizes.

The most common HR HPV types in our FSW population were HPV 16 and 52. Similarly, HPV 16 and 52 were the most commonly detected HPV types in a FSW cohort in Mombasa, a family planning clinic in Nairobi and an outpatient general clinic in Nairobi.^9,20 HPV16 was the most common HR HPV infection among HIV-1 seronegative women. The prevalence of HPV 52 appears relatively higher among women with HSIL in Kenyan women as compared with HSIL cases from geographical regions worldwide.¹⁸ A study of distribution of individual HPV types among HIV-positive women was limited by small sample size.

This sex worker population would not be an appropriate target population for HPV vaccine given the high prevalence of high-risk HPV types in this group. Young presexual women in this region would benefit greatly from access to the current HPV vaccines. Public health centres, such as the one where our clinic was located, is an ideal place for cervical cancer education and HPV vaccination as a large number of people, mostly women and children, visit the centre every day. Cervical cancer screening is necessary, even among vaccinated groups given the high prevalence of HR-HPV types that are not in the currently available vaccines (HPV 33, 45, 52 and 58) among women with high-grade lesions in this cohort and other studies of HSIL in Kenya.^9,20

HR HPV testing is being implemented in many countries as a screening tool to identify women over 30 years of age at risk of precancerous lesions. Our findings in this FSW population suggest that detection of multiple, concurrent HPV infections may also be useful as a further diagnostic tool to identify women at a high risk of precancerous lesions, although our sample sizes in Table 3 are small. A large prospective study found that Brazilian women with multiple HPV infections were at a higher risk of HSIL as compared with those with single-type infections.²¹ A large cohort study with biopsy-confirmed cytology results is needed to further elucidate the role of multiple genital HPV infection as a risk factor for precancerous lesions among HIV-1 seropositive and seronegative women. Further studies should explore whether the detection of multiple-HPV infections represents a marker for underlying immunological susceptibility to cervical neoplasia.

Declarations

The first author was a Howard Hughes Medical Institute Medical Research Training Fellow. PP was funded by a Worldwide Development Fellowship between UNC and GSK. Dr. Jennifer Smith has received research grants, served on paid advisory boards, and/or been a paid speaker for GSK, Hologic Gen-Probe, and Merck. The study was supported by GSK.

Footnotes

Acknowledgements

We thank the female sex workers who agreed to participate in this study, our clinic nurses, Ephel Kasandi and Josephine Wamgombe, for their efforts in recruitment, enrolment and follow-up of participants.

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