Cervical cancer remains one of the most formidable challenges in global oncology, ranking as the fourth most common cancer among women worldwide, and its primary driver is persistent infection with high-risk types of human papillomavirus. A new study conducted in Lagos, Nigeria, has now revealed a striking picture of which viral genotypes are actually circulating in this West African population, and the results carry uncomfortable implications for current vaccination strategies. Among 165 sexually active women recruited from a tertiary gynecology referral clinic, more than half carried at least one of the thirteen established high-risk HPV genotypes, and when five probable high-risk types were added to the analysis, the proportion of infected women climbed to just over seventy percent. The most frequently detected genotype was HPV-35, a type that is not fully covered by the vaccines most widely deployed in global immunization programs, a finding that the study’s authors argue should prompt a fundamental rethinking of region-specific vaccine design.
The research, published in BMC Infectious Diseases, was led by Oluwaseyi Sedowhe Ashaka of Caleb University in Lagos together with collaborators spanning Nigerian institutions including the Nigeria Centre for Disease Control and Prevention, Lagos University Teaching Hospital, the Nigerian Institute of Medical Research, and the University of Ilorin, along with partners at The University of Texas Rio Grande Valley in the United States. Recruitment took place between July 2017 and June 2018, and every participant underwent both conventional cervical cytology screening by Pap smear and molecular testing for HPV. The dual approach allowed the investigators to compare viral genotype distribution in women whose cervical cells appeared normal under the microscope with those whose smears showed abnormalities ranging from atypical squamous cells of undetermined significance to low-grade and high-grade squamous intraepithelial lesions, the cytological precursors of invasive cancer.
The molecular methodology at the heart of the study deserves particular attention because it goes beyond the detection limits of many routine screening assays. Rather than relying on a single amplification reaction, the team employed nested and multiplex polymerase chain reaction, a technique that uses two successive rounds of primer binding to boost sensitivity and then simultaneously amplifies genetic targets from eighteen distinct high-risk or probably high-risk HPV genotypes in the same reaction vessel. This nested multiplex PCR approach targeted thirteen established carcinogenic types, including the notorious HPV-16 and HPV-18, as well as five probable high-risk types such as HPV-82 and HPV-73, which are less commonly assayed in commercial test panels. The inclusion of these less-characterized genotypes proved consequential: HPV-82 was the second most prevalent type in the cohort at twenty percent, and HPV-73 ranked third at just over nine percent, figures that would likely have been missed by narrower testing strategies.
The headline genotype, HPV-35, was detected in 43.6 percent of the women tested, an extraordinarily high proportion that dwarfs the frequencies typically reported for this type in European and North American surveillance studies. HPV-35 belongs to the alpha-9 species of papillomaviruses, the same phylogenetic group as HPV-16, and it expresses the E6 and E7 oncoproteins that interfere with the p53 and retinoblastoma tumor suppressor pathways, the canonical molecular mechanism by which high-risk HPVs drive malignant transformation. Crucially, HPV-35 was the most frequent genotype across every cytological grade in the study, meaning it appeared not only in women with normal smears but also in those with progressively severe epithelial abnormalities. This pattern suggests that HPV-35 is not a benign passenger in this population but an active participant in the spectrum of cervical disease, consistent with accumulating evidence from other sub-Saharan African settings where non-16 and non-18 types carry a disproportionate share of the oncogenic burden.
Another notable finding was the frequency of mixed infections. Dual and multiple high-risk HPV infections were present in 34.5 percent of all participants, meaning roughly one in three women harbored two or more oncogenic genotypes simultaneously. Co-infection is biologically significant for several reasons. Multiple genotype infections can complicate viral competition and interference dynamics, may accelerate the progression of cervical lesions through additive or synergistic effects of different oncoproteins, and complicate genotype-specific surveillance because the presence of one dominant type can mask the detection of others depending on the assay used. In a clinical context, the high rate of multiple infections in Lagos underscores the limitations of screening algorithms designed around single-genotype detection and reinforces the case for broad-spectrum molecular panels in routine diagnostics.
The cytological findings provided an important clinical anchor for the molecular data. Abnormal cervical cytology was identified in 21.8 percent of the cohort, a substantial proportion reflecting the fact that participants were drawn from a gynecology referral clinic rather than a general population sample. Within this abnormal group, HPV-35 again emerged as the most frequent genotype across all grades of dysplasia, from low-grade squamous intraepithelial lesions to high-grade lesions. The persistence of a single non-vaccine genotype across the full cytological spectrum raises pointed questions about how well current screening and vaccination paradigms, which were largely calibrated on the epidemiology of HPV-16 and HPV-18, translate to populations where the genotype distribution is fundamentally different.
Beyond mapping the viral landscape, the study interrogated the behavioral and demographic risk factors associated with infection, using chi-square tests for initial comparisons and then multivariable logistic regression with Firth’s penalized-likelihood method to identify independent associations. This statistical approach is specifically designed for datasets in which some outcome categories contain few events, producing more reliable odds ratio estimates than standard maximum-likelihood regression when the data are sparse. Two factors emerged as independently associated with high-risk HPV infection after adjustment. A history of sexually transmitted infection nearly tripled the odds of carrying high-risk HPV, with an adjusted odds ratio of 3.27, while condom use was strongly protective, reducing the odds by more than eighty percent with an adjusted odds ratio of 0.19. Both associations were statistically robust, with confidence intervals that excluded the null value.
Equally instructive were the factors that did not retain statistical significance. Later sexual debut, defined in the study as first intercourse at age twenty-one or older, and a higher number of lifetime sexual partners both showed elevated odds ratios in the initial analysis, but these did not reach statistical significance after adjustment. Similarly, age, educational status, and marital status were not independently associated with infection once other variables were accounted for. This pattern suggests that in this Lagos cohort, the dynamics of viral transmission and clearance are shaped more directly by sexual behavior variables with clear mechanistic links to exposure, such as barrier protection and prior sexually transmitted infections indicating unprotected exposure, than by broader demographic categories. The strong protective effect of condom use aligns with the established biology of HPV transmission, which occurs through direct contact with infected epithelial surfaces, and it offers an immediately actionable target for public health messaging even in settings where vaccine coverage remains low.
The implications of the study extend well beyond Lagos. Most cervical cancer prevention programs worldwide rest on two pillars: vaccination against HPV-16 and HPV-18, the types responsible for the majority of cervical cancers globally, and cytological or molecular screening to detect precancerous lesions. The bivalent, quadrivalent, and nonavalent vaccines differ in the number of types they cover, with the nonavalent product adding HPV-31, 33, 45, 52, and 58 to the original pair, but none provides complete protection against HPV-35, HPV-73, or HPV-82. In a population where HPV-35 alone accounts for over forty percent of infections and the majority of detected genotypes fall outside even the broadest current vaccine formulation, the protective ceiling of existing immunization strategies is inherently limited. The authors argue that this mismatch makes a compelling case for region-specific vaccine development, potentially incorporating the genotypes that dominate African epidemiology, and for integrating molecular HPV genotyping into routine screening programs so that women carrying non-vaccine high-risk types are not falsely reassured.
The study also highlights the practical infrastructure needed to act on such findings. The molecular work relied on positive controls supplied by the WHO HPV LabNet laboratory for the African region at the University of Cape Town, illustrating the value of international laboratory networks in supporting genotype-level surveillance where commercial assay coverage is incomplete. With cervical cancer incidence and mortality in sub-Saharan Africa among the highest in the world, and screening coverage in many countries remaining far below the targets set by the World Health Organization’s global elimination strategy, data of this granularity are essential for calibrating local responses. The Lagos findings, derived from a carefully genotyped cohort with both normal and abnormal cytology, provide a template for the kind of evidence base that vaccine developers, screening program designers, and policymakers will need if the goal of eliminating cervical cancer as a public health problem is to be achieved on a timeline that matters for the generations of women currently at risk.
Subject of Research: Distribution of high-risk human papillomavirus genotypes and associated risk factors among women in Lagos, Nigeria
Article Title: Distribution of high-risk human papillomavirus genotypes and associated risk factors among women with normal and abnormal cervical cytology in Lagos, Nigeria
Article References: Distribution of high-risk human papillomavirus genotypes and associated risk factors among women with normal and abnormal cervical cytology in Lagos, Nigeria. (n.d.). https://doi.org/10.1186/s12879-026-14580-0
Image Credits: AI Generated
DOI: 10.1186/s12879-026-14580-0
Keywords: human papillomavirus, HPV-35, cervical cancer, cervical cytology, HPV genotypes, multiple HPV infections, risk factors, HPV vaccine coverage, molecular diagnostics, Nigeria, Sub-Saharan Africa, BMC Infectious Diseases
News Source: Kristina Jarvis. (October 14, 2026). High-Risk HPV Genotypes Not Covered by Vaccines Dominate Cervical Infections in Lagos Women. Scienmag.
