International Journal of Infectious Diseases

Expanding access to cervical cancer screening: The performance of self-sampled urine HPV testing

Cervical cancer remains a significant public health issue, particularly in low- and middle-income countries, where access to effective screening is limited. Urine-based human papillomavirus (HPV) testing, when combined with advanced DNA purification and concentration technologies, offers a promising alternative to traditional provider-collected cervical samples for HPV detection and cervical cancer screening. This study evaluated the performance of a urine-based HPV test utilizing DNA purification and concentration technology (the Experimental Test) in comparison to the Cobas4800 HPV test performed on provider-collected endocervical samples (the Control Test). A total of 1280 women, primarily those testing positive for high-risk HPV (HR-HPV) and with available pathology diagnoses, were included in the analysis. Concordance between the two tests was assessed for HPV-16, HPV-18, and a pooled group of 12 HR-HPV types. Sensitivity and specificity for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) were also compared. The Experimental Test demonstrated good concordance with the Control Test for detecting HPV-16 and HPV-18 (Cohen's Kappa 0.73 and 0.66 respectively), and moderate concordance for detecting the pooled 12 HR-HPV types (Kappa 0.53). In disease outcome analysis, the Experimental Test showed comparable to the Control test in term of the sensitivities in detecting CIN2+ and CIN3+ cases, but its relevant specificities are comparatively lower. Overall, the Experimental Test was noninferior to the Control Test in detecting HPV-16, HPV-18, the pooled 12 HR-HPV types, CIN2+, and CIN3+. Urine-based HPV testing using a DNA purification and concentration process is noninferior to the gold standard Cobas4800 test on provider-collected samples for the detection of high-risk HPV types and the high grades of cervical precancerous lesions. The Experimental Test provides a highly sensitive, reliable, and scalable option for cervical cancer screening, particularly in settings where traditional screening methods are less accessible.

Prevalence of cervical HPV infection, sexually transmitted infections and associated antimicrobial resistance in women attending cervical cancer screening in Mali

To assess the prevalence of sexually transmitted infections (STIs), antimicrobial resistance and cervical lesions among women from Sikasso, Mali. Women infected with human immunodeficiency virus (HIV) (n=44) and HIV-negative women (n=96) attending cervical cancer screening were included. Screening for human papillomavirus (HPV), Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) was performed using polymerase chain reaction assays, and herpes simplex virus (HSV-1/2) serological status was assessed using enzyme-linked immunosorbent assays. Antibiotic resistance tests were performed for MG- and NG-positive cases. A high prevalence of high-risk HPV (hrHPV) infection (63%) was found. This was associated with cervical lesions in 7.5% of cases. An unusual distribution was found, with HPV31, HPV56 and HPV52 being the most prevalent. The hrHPV distribution differed by HIV status, with HIV-positive cases having HPV35/31/51-52-56 and HIV-negative cases having HPV31/56/52. The seroprevalence of HSV-2 was 49%, and the prevalence of other STIs was as follows: CT, 4%; MG, 9%; NG, 1%; and TV, 7%. Five of nine MG-positive specimens and the NG strains obtained were resistant to fluoroquinolone. These results showed high prevalence of hrHPV and fluoroquinolone resistance in several NG and MG strains. Further studies are required to confirm these data in Mali, and to improve prevention, screening and management of cervical cancer and other STIs in women.

Nationwide implementation and evaluation of an external quality assessment program for HPV screening in Peru

In the global effort to eliminate cervical cancer, high-quality Human Papillomavirus (HPV) testing is essential, especially in Peru where vaccination coverage remains incomplete. To ensure consistent nationwide test performance, the Peruvian HPV National Reference Laboratory (NRL), in collaboration with the International HPV Reference Center (IHRC), launched the first nationwide External Quality Assessment (EQA) program for all screening laboratories. In 2024, 19 screening laboratories, including regional reference centers and tertiary hospitals, participated in the EQA program. Proficiency panels of 13 blinded samples with defined HPV types and viral loads were validated by IHRC and distributed by the NRL. Laboratories analyzed the samples using the Cobas 4800 HPV assay. Eighteen laboratories (94.7%) met proficiency criteria, correctly detecting all required HPV types, including low viral load samples. One laboratory reported false positives in a negative and a low-concentration HPV 18 sample. This program shows the feasibility of nationwide EQA in Peru, with full participation and reporting. Annual assessments will sustain quality assurance and equitable access to reliable HPV testing. From 2026, the Peruvian HPV NRL will coordinate the program independently, expand participation to additional laboratories, and enable local panel production-an important step toward strengthening cervical cancer screening quality.

Long-term effectiveness of at least one dose of human papillomavirus vaccine in adolescents: A test-negative case–control study

Human papillomavirus (HPV) vaccination has been recommended by the World Health Organization as part of the cervical cancer elimination strategy. Many countries have introduced single-dose or two-dose vaccination schedules. However, data on the effectiveness of at least one dose of the HPV vaccine among school-aged girls remain limited. The study was a test-negative case-control conducted to estimate the effectiveness of HPV vaccines (VE) against high-risk types of HPV among adolescents in a real-world setting. Demographics and risk factors data were collected. Cases were adolescent who tested positive for high-risk HPV DNA. Time-matched controls were those who tested negative. Overall, 760 participants with a mean (SD) age of 18.2 (2.9) years underwent for HPV DNA testing. Among 114 vaccinated participants, 34 had received one dose and 80 had received two doses; the mean (SD) time since vaccination was 65.89 (23.67) months. A total of 100 participants tested positive for high-risk HPV types. The four most common high-risk types were HPV 16, 59, 52, and 58. The overall adjusted VE against high-risk HPV types among young women with a duration of >5 years was 91.0% (95% confidence interval: 33.4-98.8). The VEs against HPV high-risk infection among the age groups 9-18, 9-15, and 9-12 years who had received at least one dose were similar for >5 years. At least one dose of the HPV vaccine was shown to be highly effective in preventing high-risk HPV types for >5 years across vaccination age up to 18 years.

Effects of different-valent vaccines against human papillomavirus (HPV) to prevent persistent HPV16/18 infections and CIN2+ in women: a systematic review and network meta-analysis

To evaluate the efficacy of 2-valent, 4-valent and 9-valent HPV vaccination in preventing persistent HPV infections and cervical intraepithelial neoplasia grade 2 or higher (CIN2+) lesions among women with different infection statuses at baseline. PubMed, Web of Science, Cochrane, Embase and ClinicalTrials.gov were searched from their inception to March 2024. Randomized controlled trials (RCTs) and post hoc analyses of RCTs reporting the risk of persistent HPV infections and CIN2+ among vaccinated women were included. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to summarize the intervention effects. Eighteen RCTs and one post hoc analysis of RCTs were included. In the according-to-protocol (ATP) cohorts, the 4-valent vaccine was the most effective against HPV16/18-related persistent infections and CIN2+ (6-month persistent infections (6mPIs): OR 0.05, 95% CI [0.02, 0.15]; 12-month persistent infections (12mPIs): OR 0.02, 95% CI [0.00, 0.18]; CIN2+: OR 0.03 95% CI [0.01, 0.17]). For the total vaccination cohorts (TVCs), the 2-valent vaccine was most effective against HPV16/18-related 12mPIs and CIN2+ (12mPIs: OR 0.15, 95% CI [0.04, 0.63]; CIN2+: OR 0.52 95% CI [0.32, 0.87]), whereas the 4-valent vaccine was most effective against HPV16/18-related 6mPIs (OR 0.08, 95% CI [0.02, 0.28]). Vaccination against HPV can significantly reduce the risk of persistent HPV16/18-related infections and CIN2+, regardless of the HPV infection prevaccination. In addition to 4- and 9-valent vaccines, 2-valent vaccines could also provide satisfactory protection against persistent HPV16/18-related infections and CIN2+, especially over the long term, and may constitute an alternative for government-led vaccination programs in developing countries.

Incident detection of human papillomavirus – a prospective follow-up study among Tanzanian women with a focus on HIV status

The causative role of human papillomavirus (HPV) in cervical carcinogenesis is well established; however, prospective studies examining high-risk(HR)-HPV acquisition among adult women in HIV-prevalent settings are limited. We conducted a prospective study among women (25-60 years) attending cervical cancer screening in Tanzania. Cervical specimens obtained at enrolment and follow-up were tested for HPV. Participants were interviewed on lifestyle and tested for HIV. Among 3805 eligible women, 3074 (80.8%) attended follow-up (median time between the 2 examinations, 17.3 months); 307 had missing HPV results at enrolment or follow-up, leaving 2767 study participants. Among 2253 women initially HR-HPV negative, 184 acquired HR-HPV-incidence: 54.5 per 1000 person-years (95% CI:47.1-62.9); among HIV-positive women 75.2 per 1000 person-years (95% CI:54.5-103.7), HIV-negative 50.9 per 1000 person-years (95% CI:43.3-60.0). HPV52 and HPV16 were the most frequently acquired types. In multivariable regression analysis, HIV positivity, low CD4 count, younger age, and multiple sexual partners were associated with increased odds of HPV acquisition. HPV acquisition was higher among HIV-positive than HIV-negative women, especially women with low CD4 counts. Improvement of immune status among HIV-positives may decrease HPV acquisition. Nonavalent HPV vaccination should be considered given the pattern of HR-HPV types acquired.

Influence of HIV infection on the distribution of high-risk HPV types among women with cervical precancerous lesions in Yaounde, Cameroon

To characterize high-risk HPV types associated with cervical precancerous lesions in women living in Yaounde, Cameroon, and to determine their distribution with HIV status. Women with abnormal pap smears recorded from February 2015 to May 2019 at Saint Martin de Porres' Health Centre, Yaounde, Cameroon, were recruited in this study after obtaining informed consent. Pap smears were collected and re-examined. Human immunodeficiency virus (HIV) serology was determined. HPV16, 18, 33, and 45 were assessed using standard PCR. All included participants (370) were HPV-positive and had either low grade squamous intraepithelial lesions (67.03%) or high grade squamous intraepithelial lesions (31.35%). They were subdivided into HIV-positive (N =102) and HIV-negative (N =268). In the HIV-negative subgroup, we observed 66.04% HPV16-positve, 41.79% HPV18-positve, 21.27% HPV33-positve and 8.21% HPV45-positve. In the HIV-positive subgroup, we observed 22.55% HPV16-positve, 5.88% HPV18-positve, 75.49% HPV33-positve, and 49.02% HPV45-positve. Married HIV-positive participants (47.14 ± 1.19) were older than both their single counterparts (34.94±1.22, P = 0.0008) and HIV-negative participants (41.43 ± 0.79, P = 0.0001). Single HIV-positive women reported higher numbers of miscarriages (P = 0.0023), and had later first sexual intercourse than HIV-negative (P = 0.0079) women. Our study suggested differential expressions in high-risk HPV types with HIV status and cervical precancerous lesions and warrants more extensive studies.

Evidence for triaging HPV-positive women using viral load: data from two large cohort-screening projects in different regions of China

To evaluate the effectiveness of viral load (VL)-based triage strategies for human papillomavirus (HPV)-positive women, utilizing data from two large cohort screening studies. We analyzed 1656 HPV-positive cases identified among 25,419 screening participants. Collected data included HPV testing, cytology, and pathologically confirmed diagnoses. VL-based triage strategies were compared to a guideline-recommended cytology-based triage. The cycle threshold (Ct) value, representing HPV VL, was used for triage, with the 75th percentile of Ct values established as the cut-off. Outcomes were assessed for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and CIN3+. The mean participant age was 43 ± 7.99 years. Two triage strategies were compared: (1) HPV-16/18 and other types with Ct ≤ the 75th percentile cut-off (higher viral load), and (2) HPV-16/18 & other types with cytology (referring those with ≥ atypical squamous cells of undetermined significance [ASCUS] for colposcopy). The VL-based strategy demonstrated higher sensitivity than the cytology-based strategy for detecting CIN2+ (91.52% vs. 85.27%, p = 0.016) and was comparable for detecting CIN3+ (95.60% vs. 96.70%, p = 1.000). Similarly, the strategy using HPV-16/18 with Ct ≤ 75th & other types with Ct ≤75th was also comparable to the cytology-based approach for detecting both CIN2+ (87.05% vs. 85.27%, p = 0.636) and CIN3+ (95.60% vs. 96.70%, p = 1.000). Viral load-based triage effectively identifies cervical precancer/ cancer in HPV-positive individuals without cytology, allows single-sample collection, reduces multiple visits, and may be most useful where cytology is unavailable or unreliable-acknowledging an increased colposcopy referral.