The research, published in BMC Public Health, is a prospective cohort study led by Madleen Orumaa of the Cancer Registry of Norway together with collaborators from the Danish Cancer Institute, Karolinska Institutet in Sweden, and the Icelandic Cancer Registry. The team analyzed data from 117,511 women aged 18 to 45 in Norway, Sweden, Denmark and Iceland who completed detailed questionnaires about cervical cancer risk factors, including sexual history, contraceptive use, smoking, and prior sexually transmitted infections. The women were then followed for a mean of 9.5 years through national health registries, allowing the researchers to link self-reported lifestyle information collected before diagnosis with subsequent outcomes.

During follow-up, the cohort accumulated a meaningful set of endpoints: 2,926 women were diagnosed with cervical intraepithelial neoplasia grade 3, or CIN3, the principal squamous precursor lesion; 174 developed adenocarcinoma in situ, the glandular equivalent; 66 were diagnosed with invasive squamous cell carcinoma; and 23 with invasive adenocarcinoma. Because glandular lesions are comparatively rare, the absolute numbers are small, and the authors themselves frame the findings as an important first step rather than a definitive answer. Even so, the prospective design — recording exposures before any diagnosis — gives the associations considerably more credibility than retrospective case-control studies, which are vulnerable to recall bias after a cancer diagnosis.

The statistical analysis used multivariate Cox regression, a technique that estimates hazard ratios for each exposure while adjusting for all the others, thereby isolating the independent contribution of each lifestyle factor. The results split cleanly along histological lines. For the squamous pathway — CIN3 and squamous cell carcinoma combined — four factors emerged as independently associated with risk. Each additional lifetime sexual partner raised the hazard by roughly 47 percent, with an adjusted hazard ratio of 1.47 and a 95 percent confidence interval of 1.34 to 1.56. A reported history of chlamydia infection carried a hazard ratio of 1.43 (95 percent CI: 1.31 to 1.56). Use of hormonal contraceptives was associated with a hazard ratio of 1.23 (95 percent CI: 1.02 to 1.47), and smoking added a small but measurable increment of 2 percent per pack-year (hazard ratio 1.02, 95 percent CI: 1.02 to 1.03).

The glandular pathway told a different story. Women who went on to develop adenocarcinoma in situ or invasive adenocarcinoma did share some baseline characteristics with the squamous group — both groups reported an earlier age at first intercourse and a greater number of lifetime sexual partners compared with women who remained unaffected. But in the fully adjusted models, one factor stood out as specific to the glandular lesions: a history of genital warts, which are caused by low-risk HPV types 6 and 11, was associated with a hazard ratio of 1.60 (95 percent CI: 1.15 to 2.24) for AIS/AC. Notably, this association did not hold for the squamous lesions, suggesting that a visible history of warts may serve as a marker of a distinct pattern of HPV exposure or of individual susceptibility relevant to glandular transformation.

From a biological standpoint, the divergence is plausible. Squamous cells on the ectocervix and glandular cells in the endocervical canal are different cell types with different vulnerabilities to HPV-mediated transformation, and squamous and adenocarcinomas differ in their genomic profiles and their responses to treatment. The transformation zone, where squamous and glandular epithelia meet, is the epicenter of HPV-driven carcinogenesis, but the mechanisms by which co-factors such as smoking, hormonal exposure, and co-infections accelerate progression may not act identically in both cell lineages. Smoking, for example, is thought to act partly through local immunosuppression and the delivery of carcinogenic metabolites in cervical mucus, while hormonal contraceptives have been hypothesized to influence gene expression in HPV-infected cells. Chlamydia, meanwhile, may contribute through chronic inflammation that facilitates HPV persistence.

The public health implications are considerable. The World Health Organization has set an ambitious global strategy to eliminate cervical cancer as a public health problem, built on three pillars: HPV vaccination, screening, and treatment of precancerous lesions. Most current screening programs were designed and validated in an era when squamous lesions dominated, and they rely primarily on cytology of the transformation zone. Glandular lesions, which sit higher in the endocervical canal and shed cells less readily, are notoriously under-detected by conventional Pap smears. The authors argue that their findings underscore the need for risk-based screening models — stratifying women by their individual risk profiles rather than applying a uniform interval to everyone — and for improving adherence to screening guidelines across both lesion types.

Such risk stratification could, in principle, incorporate the factors identified in this study. A woman with a history of chlamydia, extensive smoking exposure, and multiple sexual partners might warrant closer surveillance for squamous lesions, while a history of genital warts might flag elevated glandular risk. HPV vaccination, which protects against the high-risk types responsible for most cervical cancers and, in the quadrivalent and nonavalent vaccines, against the wart-causing types 6 and 11 as well, remains the most powerful preventive tool for both pathways. The study’s finding that genital warts mark glandular risk adds an intriguing dimension: vaccination against types 6 and 11 may confer benefits beyond preventing the warts themselves, potentially reducing a marker-associated risk of glandular neoplasia.

The authors are careful to note the limitations inherent in their design. The number of invasive adenocarcinoma cases — 23 — is small, which widens confidence intervals and limits the granularity of subgroup analyses. Lifestyle data were self-reported and therefore subject to misclassification, and the cohort comprised Nordic women aged 18 to 45 at enrollment, a relatively homogeneous, well-screened population whose findings may not generalize directly to settings with different screening coverage or HPV type distributions. The study was funded by Merck & Co. for questionnaire data collection and by the Nordic Cancer Union for manuscript preparation, with the sponsors having no role in data analysis or interpretation, according to the published disclosures.

Even with those caveats, the study represents one of the largest prospective efforts to disentangle the lifestyle epidemiology of the two cervical cancer pathways, and it arrives at a moment when adenocarcinoma’s rising share of cervical cancer diagnoses is drawing increasing attention worldwide. As vaccination programs mature and screening technologies shift toward HPV testing, understanding which co-factors drive which lesion type will be essential for designing the next generation of prevention strategies. The Nordic registries, with their near-complete follow-up, offer an unusually clear window onto that question — and this study suggests the window reveals two distinct diseases, not one.

Subject of Research: Lifestyle risk factors for glandular and squamous cervical neoplasia in a Nordic prospective cohort

Article Title: Lifestyle risk factors for cervical glandular and squamous cell neoplasia: insights from a prospective cohort study of over 117,000 women

Article References: Orumaa, M., Kjaer, S. K., Munk, C., Sundström, K., Tryggvadóttir, L., Campbell, S., Hetland Falkenthal, T. E., Nygård, S., & Nygård, M. (2026). Lifestyle risk factors for cervical glandular and squamous cell neoplasia: insights from a prospective cohort study of over 117,000 women. BMC Public Health. https://doi.org/10.1186/s12889-026-29877-7

Image Credits: AI Generated

DOI: 10.1186/s12889-026-29877-7

Keywords: cervical cancer, HPV, adenocarcinoma, squamous cell carcinoma, CIN3, adenocarcinoma in situ, smoking, hormonal contraceptives, chlamydia, genital warts, prospective cohort study, cancer screening

The technical approach behind these numbers is worth noting. Rather than relying on a single broad screening assay, the team used polymerase chain reaction amplification combined with flow-through hybridization, a method that allows simultaneous detection and identification of 21 distinct HPV genotypes. This matters because HPV is not one pathogen but a family of more than 200 related viruses, only some of which are classified as high-risk for cancer. Distinguishing which genotypes circulate in a given population is essential for predicting how well existing vaccines will perform and for designing regional screening programs that target the types actually present.

The five most frequently detected genotypes among the men were HPV6, HPV52, HPV16, HPV51, and HPV42. This list mixes low-risk and high-risk types: HPV6 and HPV42 are classified as low-risk, typically associated with genital warts rather than malignancy, while HPV52, HPV16, and HPV51 belong to the high-risk category linked to anogenital and oropharyngeal cancers. HPV16 is the single most carcinogenic genotype worldwide and a dominant driver of HPV-positive cancers in both sexes. The fact that it ranks among the top types in these male outpatients reinforces why vaccination and, eventually, male screening remain central to cancer prevention efforts.

One of the study’s most striking findings is the overlap between the genotypes circulating in men and those previously reported in local women in the Putian region. The predominant types in the male cohort, including low-risk HPV6 and HPV42 and high-risk HPV52, HPV51, and HPV16, substantially mirror the genotype distribution described for females in the same area. Such concordance is consistent with sexual transmission within partner networks and suggests that vaccinating or screening only one sex leaves a persistent viral reservoir in the other. The authors argue that this overlap supports including men in HPV prevention strategies and may inform future evaluation of partner-oriented prevention approaches, in which couples are considered jointly rather than in isolation.

Age emerged as a significant axis of variation. Prevalence was highest among patients older than 60 years, a pattern that contrasts with the classic bimodal age distribution often described in women, where infection peaks in young adulthood and again around midlife. In men, clearance of infection can be less efficient with age, and cumulative exposure over a lifetime may raise the probability of detectable infection in older age groups. The researchers also conducted sensitivity analyses using broader age categories, combining the 51-to-60 and over-60 groups, to confirm the robustness of the association between older age and high-risk HPV infection, indicating that the age signal was not an artifact of how the categories were drawn.

Clinical diagnosis also shaped the picture. HPV prevalence varied significantly across the six diagnostic subgroups into which patients were stratified: warts, urinary tract infections, dermatitis, genital diseases, health check-ups, and others. The warts group showed the highest infection rate at 48.7 percent, dominated by HPV6 and HPV11, the two low-risk genotypes most classically responsible for condyloma acuminatum, or genital warts. That result is biologically coherent, since patients presenting with visible warts are, by definition, already expressing an HPV-driven lesion. More unexpected was the dermatitis group, which came in a close second at 46.5 percent and displayed remarkable genotype diversity, with HPV52, HPV16, HPV42, HPV51, and HPV59 all appearing among the detected types.

The dermatitis finding carried enough statistical weight to survive multivariable regression analysis. After adjusting for other variables, dermatitis was identified as an independent risk factor for high-risk HPV infection, with the authors reporting an adjusted odds ratio and controlling for confounding using generalized variance inflation factors to check for collinearity among predictors. The biological interpretation is not settled from these data alone, but plausible mechanisms include disruption of the skin barrier providing an easier entry point for virions, local immune dysregulation reducing viral clearance, or inflammatory conditions serving as a marker for behaviors or exposures that also raise HPV risk. Whatever the direction of causality, the association suggests that dermatology clinics could represent an underused point of contact for HPV testing in men.

The vaccine analysis is where the study’s public health implications become most concrete. China’s regional vaccination programs have historically focused on girls and women, and the 9-valent HPV vaccine, which protects against genotypes 6, 11, 16, 18, 31, 33, 45, 52, and 58, is the broadest formulation in widespread use. Yet even against this nine-type panel, the researchers calculated that 33.5 percent of HPV-positive men in the cohort carried at least one genotype not covered by the vaccine, and the coverage gap was nearly identical, at 33.9 percent, among men carrying high-risk types. In other words, roughly one third of infections, including those with cancer-associated potential, would not be prevented by the current nonavalent vaccine, a gap driven by types such as HPV51 and HPV59 that fall outside the formulation.

These coverage gaps do not diminish the case for vaccination, but they do complicate it. On one hand, the predominance of HPV6, HPV16, and HPV52 in the male cohort means the 9-valent vaccine would still address a majority of circulating infections, and HPV16 in particular is responsible for a disproportionate share of HPV-related cancers. On the other hand, the persistence of a substantial non-vaccine reservoir means that vaccination alone cannot eliminate transmission in this population, and the finding strengthens arguments for extending vaccination to boys and men, both to protect them directly against cancers and warts and to build herd protection that benefits unvaccinated partners.

The study has limitations inherent to its design. It was retrospective and drew exclusively on male outpatients at a single hospital in Putian, a prefecture-level city in Fujian Province, so the 35.2 percent prevalence cannot be generalized to the general male population, which typically shows lower rates than clinic-based cohorts. Patients visiting dermatology or urology clinics are more likely to have conditions related to or coinciding with HPV infection than men sampled at random. The ethics committee of the First Hospital of Putian City approved the study and granted an exemption from individual informed consent, and the authors declare no competing interests. Even with those caveats, the work fills a genuine gap: no previous research on male HPV prevalence in Putian had been reported, and region-specific genotype data of this kind are scarce across much of China.

The broader takeaway is that HPV epidemiology in men deserves the same granular, genotype-level attention that has long been applied to women. As vaccination programs expand and as oropharyngeal and anal cancers linked to HPV rise in many countries, understanding which types circulate in male populations, at which ages, and in association with which clinical conditions becomes essential for modeling transmission, forecasting vaccine impact, and deciding whether and when to introduce routine male screening. The Putian data, with their high prevalence, distinctive age gradient, dermatitis signal, and measurable vaccine gap, offer a template for the kind of local surveillance that global HPV control efforts will increasingly require.

Subject of Research: Prevalence and genotype distribution of human papillomavirus infection among male outpatients in Putian, Fujian Province, China

Article Title: Prevalence and genotype distribution characteristics of human papillomavirus infection among male outpatients in Putian, Fujian Province: a retrospective study

Article References: Chen, Y., Xiao, G., Chen, A., Zhang, R., & Zhang, L. (2026). Prevalence and genotype distribution characteristics of human papillomavirus infection among male outpatients in Putian, Fujian Province: a retrospective study. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14565-z

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14565-z

Keywords: HPV, human papillomavirus, male HPV prevalence, genotype distribution, HPV vaccination, 9-valent vaccine, high-risk HPV, genital warts, dermatitis, China, epidemiology, BMC Infectious Diseases