Sexually Transmitted Infections

Self-collection for high-risk HPV-RNA detection among HIV-seropositive and HIV-seronegative women engaged in sex work in Kenya

Background Evidence of self-collection human papillomavirus (HPV)-RNA testing in cervical cancer screening is limited among women with HIV (WHIV). Most studies are in low-risk patient populations in high-income countries. We examine the prevalence of high-risk HPV (hrHPV) using the APTIMA HPV-RNA assay on self-collected versus provider-collected specimens, and the associated risk factors for high-grade cervical intraepithelial neoplasia (CIN2/3) among women engaged in sex work in Kenya. Among WHIV, we examine the performance of both collection methods for the detection of CIN2/3. Methods Participants were aged ≥18 years, non-pregnant and had no previous treatment for cervical precancer. The screening process included self-collection of cervicovaginal samples using a Viba cytobrush (Rovers), provider-collected cervical samples, visual inspection with acetic acid (VIA) and Pap smear. The APTIMA HPV Assay (Hologic) was used to detect E6/E7 oncogene RNA of 14 hrHPV types in both self-collected and on provider-collected samples. Risk factors for CIN2/3 were determined via multivariable logistic regression. We estimated test characteristics for each screening method for CIN2/3 detection. Results A total of 400 women (194 WHIV, 206 women without HIV) underwent screening between 2013 and 2018, with 399 valid HPV results. WHIV had a higher prevalence of hrHPV by self-collection compared with women without HIV (44.0% vs 29.6%, p<0.05) and CIN2/3 (19.0% vs 9.7%, p<0.05). After adjusting for age and HIV status, hrHPV-positivity increased the risk of CIN2/3 by 13 to 20 times. Among WHIV, the sensitivity for CIN2/3 detection was similar between self-collection (85% (66-96)) and provider-collection (93% (76-99)), both of which were higher than the sensitivity of high-grade cytology (high-grade squamous intraepithelial lesion cut-off) (47% (95% CI 23 to 72)). The specificity for both collection methods (self: 66% (95% CI 57 to 75) and provider: 67% (95% CI 58 to 75)) was lower than cytology (85% (95% CI 78 to 91)). Conclusion Self-collection for HPV-RNA testing performed similarly to provider-collection among WHIV. For WHIV, while the higher sensitivity of HPV-RNA testing compared with cytology for the detection of clinically relevant cervical disease is important, the lower specificity supports the inclusion of a triage test in the screening algorithm.

HPV types, cervical high-grade lesions and risk factors for oncogenic human papillomavirus infection among 3416 Tanzanian women

ObjectiveThe objective of the present study was to assess the prevalence and type-specific distribution of cervical high-risk (HR) human papillomavirus (HPV) among women with normal and abnormal cytology, and to describe risk factors for HR HPV among HIV-positive and HIV-negative women in Tanzania.MethodologyA cross-sectional study was conducted in existing cervical cancer screening clinics in Kilimanjaro and Dar es Salaam. Cervical specimens were obtained from women aged 25–60 years. Samples were shipped to Denmark for cytological examination, and to Germany for HR HPV testing (using Hybrid Capture 2) and genotyping (using LiPaExtra). Risk factors associated with HPV were assessed by multivariable logistic regression analysis.ResultAltogether, 4080 women were recruited with 3416 women contributing data for the present paper, including 609 HIV-positive women and 2807 HIV-negative women. The overall HR HPV prevalence was 18.9%, whereas the HR HPV prevalence in women with high-grade squamous intraepithelial lesions (HSILs) was 92.7%. Among HPV-positive women with HSIL, HPV16 (32.5%) and HPV58 (19.3%) were the the most common types followed by HPV18 (16.7%) and HPV52 (16.7%). Factors associated with HR HPV included younger age, increasing number of partners and early age at first intercourse. Similar risk factors were found among HIV-positive and HIV-negative women. In addition, among HIV-positive women, those with CD4 counts <200 cells/mm3had an increased risk of HR HPV (OR 2.2; 95% CI 1.2 to 4.8) compared with individuals with CD4 count ≥500 cells/mm3.ConclusionGiven the HPV distribution among Tanzanian women, the current HPV vaccination in Tanzania using quadrivalent vaccine may be considered replaced by the nonavalent vaccine in the future. In addition, appropriate antiretroviral treatment management including monitoring of viremia may decrease the burden of HR HPV in HIV-positive women.

Identification of human papillomavirus in oral rinse specimens from women with and without cervical intraepithelial lesions

Objectives The objective of this study was to evaluate the frequency of human papillomavirus (HPV) in the oral cavity of women with and without abnormal cervical cytology and to determine whether there is an association of oral HPV infection with infection of the cervix or with cervical cancer precursor lesions. Methods The present study was conducted among 406 women, aged 18–82 years, who attended the Prevention Department of Barretos Cancer Hospital (HCB), Brazil due to a previous altered cervical cytology result. Oral rinse, cervical cytology and biopsy were collected at the same day. The participants also answered a questionnaire about socioeconomic characteristics and risk factors for cervical cancer. Molecular screening for HPV16, HPV18 and 12 other high-risk HPV types was performed on cervical and oral rinse specimens using Cobas 4800 (Roche Molecular Systems, USA). Results HPV was detected in the oral rinse of 3.9% of participants. Infection of the oral cavity with a non-HPV16 or 18 type was most frequent (81.2%), followed by HPV16 (18.7%). Infection with HPV in the cervix and oral cavity was present in 11 (2.7%) of participants. There were no differences observed in the smoking status (p value 0.62), mean age of first sexual intercourse (p value 0.25), mean age of the first oral sex (p value 0.90) or mean lifetime number of sexual partners (p value 0.08) between the participants with oral HPV infection or not. Conclusion The presence of HPV infection in the oral cavity was low in the group of women with abnormal cervical cancer screening findings and a high rate of cervical HPV infection.

Human papillomavirus and abnormal cervical lesions among HIV-infected women in HIV-discordant couples from Kenya

Objective HIV infection increases the risk of high-grade cervical neoplasia and invasive cervical carcinoma. The study addresses the limited data describing human papillomavirus (HPV) infection and cervical neoplasia among HIV-infected women in HIV-discordant relationships in sub-Saharan Africa, which is needed to inform screening strategies. Methods A cross-sectional study of HIV-infected women with HIV-uninfected partners was conducted to determine the distribution of type-specific HPV infection and cervical cytology. This study was nested in a prospective cohort recruited between September 2007 and December 2009 in Nairobi, Kenya. Cervical cells for HPV DNA testing and conventional cervical cytology were collected. HPV types were detected and genotyped by Roche Linear Array PCR assay. Results Among 283 women, the overall HPV prevalence was 62%, and 132 (47%) had ≥1 high-risk (HR)-HPV genotype. Of 268 women with cervical cytology results, 18 (7%) had high-grade cervical lesions or more severe by cytology, of whom 16 (89%) were HR-HPV-positive compared with 82 (41%) of 199 women with normal cytology (p<0.001). The most common HR-HPV types in women with a high-grade lesion or more severe by cytology were HPV-52 (44%), HPV-31 (22%), HPV-35 (22%), HPV-51 (22%) and HPV-58 (22%). HR-HPV genotypes HPV-16 or HPV-18 were found in 17% of women with high-grade lesions or more severe. HR-HPV screening applied in this population would detect 89% of those with a high-grade lesion or more severe, while 44% of women with normal or low-grade cytology would screen positive. Conclusion HR-HPV prevalence was high in this population of HIV-infected women with an uninfected partner. Choice of screening for all HR genotypes versus a subset of HR genotypes in these HIV-infected women will strongly affect the performance of an HPV screening strategy relative to cytological screening. Regional and subpopulation differences in HR-HPV genotype distributions could affect screening test performance.

Increasing human papilloma virus (HPV) vaccination uptake in people living with HIV: the need to improve both clinician training and health promotion

Acquired lymphangioma circumscriptum of the vulva secondary to severe herpes simplex infection

High burden of human papillomavirus and premalignant cervical lesions among women starting HIV treatment in KwaZulu-Natal, South Africa

ObjectivesHuman papillomavirus (HPV) can cause cervical cancer, a leading cause of female cancer mortality in South Africa and worldwide. We assessed the burden of, and factors associated with, HPV infection using a molecular assay and cervical cytology among women living with HIV (WLHIV) in South Africa.MethodsIn this cross-sectional analysis, WLHIV initiating antiretroviral therapy (ART) underwent cervical Xpert HPV testing and liquid-based cytology. The Xpert test detects 14 high-risk (hr) HPV types reported in a pooled qualitative result. We evaluated clinical and sociodemographic variables and proportions between women testing positive and negative for hr-HPV, compared cytology with hr-HPV results and assessed associations with HPV positivity.ResultsWe enrolled 260 WLHIV, median age 31.0 (IQR 26.0–38.0) years. Overall, 91.3% of women were never screened for cervical cancer previously and none received HPV vaccination. In total, 67.3% (175/260) of women tested positive for any hr-HPV type, of which HPV16 and HPV18/45 were detected in 17.3% (45/260) and 22.7% (59/260) of women, respectively, and 56.5% (147/260) tested positive for 11 other hr-types. Of 258 WLHIV, 33.3% (86/258) had abnormal cytology: high-grade squamous intraepithelial lesion (SIL) 7.8% (20/258), low-grade SIL 24.0% (62/258) and atypical squamous cells of undetermined significance 1.6% (4/258). Of these, 93.0% (80/86) tested positive for hr-HPV: 30.0% (24/80) for HPV16, 31.3% (25/80) for HPV18/45 and 92.5% (74/80) for other hr-HPV types. Having a CD4 count<200 cells/µL was associated with hr-HPV infection (adjusted prevalence ratio 2.24; 95% CI 1.69 to 2.99 (p<0.001)).Conclusionshr-HPV infection and cervical abnormalities are common among WLHIV starting ART, especially those with low CD4 counts, highlighting that early HIV testing and treatment initiation must be prioritised together with cervical cancer screening. The diversity of hr-HPV types suggests a need for vaccines with expanded HPV type coverage in this setting.

Timing of HPV vaccination as adjuvant treatment of CIN2+ recurrence in women undergoing surgical excision: a meta-analysis and meta-regression

ObjectiveThe main aim was to determine the overall vaccine effectiveness (VE) against recurrent cervical intraepithelial neoplasia grade 2 or worse (CIN2+) including specific VE associated with timing of human papillomavirus (HPV) vaccination using data from published studies.DesignMeta-analysis and meta-regression.Data sourcesA computerised literature search was undertaken using the MEDLINE, EMBASE, International Pharmaceutical Abstracts, Derwent Drug File, ProQuest Science and Technology, Cochrane and MedRxiv databases. To be eligible, the studies, with no language restrictions, had to be published between 1 January 2001 and 25 May 2023.Review methodsIncluded were studies with an unvaccinated reference group that assessed CIN2+ recurrence irrespective of the HPV genotype in women undergoing conisation provided. The present study was carried out in compliance with the Preferred Reporting Items for Systematic Review and Meta-Analyses and Meta-analysis Of Observational Studies in Epidemiology guidelines. The risk of study bias was assessed using the Newcastle–Ottawa Quality Assessment Scale. The Grading of Recommendations Assessment, Development, and Evaluation guidelines were used to assess the strength of evidence for the primary outcome. Data synthesis was conducted using meta-analysis and meta-regression.ResultsOut of a total of 14 322 publications, 20 studies with a total of 21 estimates were included. The overall VE against recurrent CIN2+ irrespective of the HPV genotype achieved 69.5% (95% CI: 54.7% to 79.5%). While the HPV vaccine valency, follow-up duration, type of study including its risk of bias had no effect on VE, the highest VE of 78.1% (95% CI: 68.7% to 84.7%) was reported for women receiving their first dose not earlier than the day of excision. This outcome was supported by additional analyses and a VE prediction interval ranging from 67.1% to 85.4%.ConclusionsThe outcome of this meta-analysis and meta-regression convincingly showed the beneficial effect of post-excisional HPV vaccination against CIN2+ recurrence. Studies published to date have been unable to determine whether or not vaccination, completed or initiated before conisation, would be associated with more favourable results.PROSPERO registration numberCRD42022353530.

Increasing the perceived relevance of cervical screening in older women who do not plan to attend screening

ObjectivesUptake of cervical screening among women aged 50–64 years is declining. Not feeling at risk because of current sexual behaviour is a reason some older women give for not being screened. We hypothesised that explaining the long interval between acquiring human papillomavirus (HPV) and developing cervical cancer would increase the relevance of screening in older women.MethodsWomen aged 50–64 years (n=597) who did not intend to go for screening were recruited through an online panel and randomised to one of three information conditions:cause only(basic information about HPV and cervical cancer),cause with basic timeline(also read a sentence describing the long interval between acquiring HPV and developing cervical cancer) andcause with explicit timeline(read the same as the timeline group alongside an explanation of what this means for older women). Perceived risk of cervical cancer, screening intention strength and understanding of HPV were assessed preinformation and postinformation exposure.ResultsInformation condition was significantly associated with risk perceptions and intention strength postintervention (F(2,593)=6.26, p=0.002 and F(2,593)=4.98, p=0.007 respectively). Women in thecause with explicit timelinecondition were more likely to increase their risk perceptions and intention strength compared withcause only(24% vs 9% and 25% vs 13% for risk perceptions and intention, respectively). In thecause with explicit timelinegroup, women with 4–10 lifetime partners had higher odds of increasing their perceived risk and intention strength postintervention compared with those with 0–1 partners (OR=2.27, 95% CI 1.01 to 5.12 and OR=3.20, 95% CI 1.34 to 7.67, respectively).ConclusionsProviding a clear explanation that decouples women’s perceived cervical cancer risk from their current sexual behaviour has the potential to increase perceived risk of cervical cancer and intentions to be screened among older women. Providing women with a clear cognitive representation of the aetiology of cervical cancer may be one approach to increasing screening uptake.

Patterns of anxiety and distress over 12 months following participation in HPV primary screening

ObjectivesMany countries are now using primary human papillomavirus (HPV) testing for cervical screening, testing for high-risk HPV and using cytology as triage. An HPV-positive result can have an adverse psychological impact, at least in the short term. In this paper, we explore the psychological impact of primary HPV screening over 12 months.MethodsWomen were surveyed soon after receiving their results (n=1133) and 6 (n=762) and 12 months (n=537) later. Primary outcomes were anxiety (Short-Form State Anxiety Inventory-6) and distress (General Health Questionnaire-12). Secondary outcomes included concern, worry about cervical cancer and reassurance. Mixed-effects regression models were used to explore differences at each time point and change over time across four groups according to their baseline result: control (HPV negative/HPV cleared/normal cytology and not tested for HPV); HPV positive with normal cytology; HPV positive with abnormal cytology; and HPV persistent (ie, second consecutive HPV-positive result).ResultsWomen who were HPV positive with abnormal cytology had the highest anxiety scores at baseline (mean=42.2, SD: 15.0), but this had declined by 12 months (mean=37.0, SD: 11.7) and was closer to being within the ‘normal’ range (scores between 34 and 36 are considered ‘normal’). This group also had the highest distress at baseline (mean=3.3, SD: 3.8, scores of 3+ indicate case-level distress), but the lowest distress at 12 months (mean=1.9, SD: 3.1). At 6 and 12 months, there were no between-group differences in anxiety or distress for any HPV-positive result group when compared with the control group. The control group were less concerned and more reassured about their result at 6 and 12 months than the HPV-positive with normal cytology group.ConclusionsOur findings suggest the initial adverse impact of an HPV-positive screening result on anxiety and distress diminishes over time. Specific concerns about the result may be longer lasting and efforts should be made to address them.

How did the COVID-19 pandemic affect access to condoms, chlamydia and HIV testing, and cervical cancer screening at a population level in Britain? (Natsal-COVID)

Objectives To investigate how differential access to key interventions to reduce STIs, HIV and their sequelae changed during the COVID-19 pandemic. Methods British participants (18–59 years) completed a cross-sectional web survey 1 year (March–April 2021) after the initial lockdown in Britain. Quota-based sampling and weighting resulted in a quasi-representative population sample. We compared Natsal-COVID data with Natsal-3, a household-based probability sample cross-sectional survey (16–74 years) conducted in 2010–2012. Reported unmet need for condoms because of the pandemic and uptake of chlamydia testing/HIV testing/cervical cancer screening were analysed among sexually experienced participants (18–44 years) (n=3869, Natsal-COVID; n=8551, Natsal-3). ORs adjusted for age and other potential confounders describe associations with demographic and behavioural factors. Results In 2021, 6.9% of women and 16.2% of men reported unmet need for condoms because of the pandemic. This was more likely among participants: aged 18–24 years, of black or black British ethnicity, and reporting same-sex sex (past 5 years) or one or more new relationships (past year). Chlamydia and HIV testing were more commonly reported by younger participants, those reporting condomless sex with new sexual partners and men reporting same-sex partners; a very similar distribution to 10 years previously (Natsal-3). However, there were differences during the pandemic, including stronger associations with chlamydia testing for men reporting same-sex partners; with HIV testing for women reporting new sexual partners and with cervical screening among smokers. Conclusions Our study suggests differential access to key primary and secondary STI/HIV prevention interventions continued during the first year of the COVID-19 pandemic. However, there was not strong evidence that differential access has changed during the pandemic when compared with 2010–2012. While the pandemic might not have exacerbated inequalities in access to primary and secondary prevention, it is clear that large inequalities persisted, typically among those at greatest STI/HIV risk.