Two-Year Incidence and Cumulative Risk and Predictors of Anal High-Grade Squamous Intraepithelial Lesions (Anal Precancer) Among Women With Human Immunodeficiency Virus.

BACKGROUND: Detection and treatment of anal histologic high-grade squamous intraepithelial lesions (hHSIL) prevents anal cancer. However, anal hHSIL incidence among women with human immunodeficiency virus (HIV, WHIV) remains unknown. Performance of anal high-risk human papillomavirus ([hr]HPV), anal cytology (anal-cyt), and both for hHSIL detection longitudinally over 2 years also remains undetermined. METHODS: We determined 2-year incidence and cumulative risk estimates (2-y-CR) of anal hHSIL among WHIV using prevalence and incidence (per 100 person-years [py]) observations stratified by baseline hrHPV and/or anal-cyt results. RESULTS: In total, 229 WHIV with complete baseline data were included in the analysis; 114 women without prevalent anal hHSIL were followed with 2 annual evaluations. Median age was 51, 63% were Black, and 23% were Hispanic. Anal hrHPV or abnormal anal-cyt was associated with an increased risk of incident anal hHSIL at 2 years (18.9/100py [95% confidence interval {CI} 11.4-31.3] and 13.4/100py [95% CI 8.0-22.7], respectively) compared with no detection of anal HPV or negative cytology (2.8/100py [95% CI 1.1-7.4] and 4.2 [95% CI, 1.8-10.2]) The presence of anal hrHPV with abnormal cytology was associated with 2-y-CR of anal hHSIL of 65.6% (95% CI 55.4%-75%); negative hrHPV with negative cytology was associated with 2-y-CR of anal hHSIL of 9.2% (95% CI 7.0-16.0). CONCLUSIONS: Detection of anal hrHPV or abnormal anal cytology are comparable predictors for 2-y-CR of anal hHSIL. The absence of anal hrHPV combined with negative cytology was predictive of a lower (but measurable) risk of developing anal hHSIL. These findings provide important data to inform anal cancer screening guidelines for WHIV.

Prevalence of anal high-risk human papillomavirus (HR-HPV) types in people living with HIV and a history of cancer.

This study aimed to describe the prevalence of high-risk human papillomavirus (HR-HPV) types in the anal canal in a cohort of people living with HIV (PLWHIV) with a history of malignancy. SETTING: Referral tertiary care hospital for adult patients with cancer. METHODS: We reviewed data of patients from the AIDS Cancer Clinic on antiretroviral therapy in chronic control who were consecutively referred for high-resolution anoscopy (HRA), where they underwent anal evaluation, collection of specimens for anal cytology and anal human papillomavirus (HPV) followed by HRA with directed biopsy if needed. RESULTS: A total of 155 patients were included; 149 (96.1%) were men, all of them men who have sex with men (MSM); the median age was 39 (IQR 32-47) years; 105 (67.7%) with Kaposi sarcoma, 40 (25.8%) with non-Hodgkin lymphoma and 10 (6.4%) with other neoplasms; only 7 (4.5%) had active cancer. The prevalence of HR-HPV infection was 89% (n=138) (95% CI 83-93) with at least one HR-HPV infection, and 62% (96) had coinfection with at least two types; the median HR-HPV types of coinfection were 3 (IQR 2-4). The number of patients infected with HPV 16 was 64 (41.3%, 95% CI 33.8-49.3), HPV 18 was 74 (47.7%, 95% CI 39.9-55.7) and with both 35 (22.6%). Some 59 patients (38%) had high-grade squamous intraepithelial lesions (HSIL) and 49 (31.6%) had low-grade squamous intraepithelial lesions (LSIL). The prevalence of HR-HPV and HSIL among patients aged ≤35 and >35 years was the same. CONCLUSIONS: In this cohort of PLWHIV with a history of malignancy we found a high prevalence of HR-HPV 16 and 18 and anal HSIL, even in persons aged ≤35 years. These data highlight the importance of anal cancer screening in PLWHIV and history of malignancy.

Should we use risk selection tests for HPV 16 and/or 18 positive cases: Comparison of p16/Ki67 and cytology.

Major screening abnormalities in precolposcopic stage are tests results that imply direct referral to colposcopy (and/or expedited treatment) without performing additional high-grade squamous intraepithelial lesions or worse (HSIL+) risk selection testing. Currently, both clinically validated HSIL+ risk selection tests, reflex cytology and reflex p16/Ki67 dual staining (DS), are being compared for use in primary human papillomavirus (HPV)-based screening to avoid possible overtreatment, but there is still no sufficient data available for their performance. Among 30 066 liquid-based cervical cancer screening tests results, a group of 332 women was selected with available high-risk types of HPV tests results with 16/18 limited genotyping, liquid-based cytology, DS, and histology results from standardized colposcopy with biopsy. In HPV 16/18+ cases, three triage approaches were retrospectively analyzed. Predictive values for detection of HSIL+ were calculated and number of colposcopies required in each strategy. Both triage models with DS used (reflex cytology followed by DS, and reflex DS alone in all cases) had significantly higher positive predictive value for HSIL+ than strategy with reflex cytology alone (44.2%/45.7% vs. 28.3%; p < 0.0001). In models with DS, less colposcopies were required (95/92 vs. 152) and less colposcopies were needed per HSIL+ detection (2.26/2.19 vs. 3.54). Only one HSIL+ case was missed in both triage models with DS incorporation. p16/Ki67 dual-stain may be an effective, alone or combined with cytology, triage test to detect HSIL+ in patients with major screening abnormalities in primary HPV-based cervical cancer screening. Performing cytology as the first triage test improves the strategy by enabling referrals to expedited treatment in selected cases.

Epidemiological distribution of high-risk human papillomavirus genotypes and associated factors among patients with esophageal carcinoma at Bugando medical center in Mwanza, Tanzania.

BACKGROUND: Esophageal carcinoma is a growing concern in regions that have a high incidence of human papillomavirus (HPV) infection such as East Africa. HPV, particularly the high-risk genotypes, is increasingly recognized as a risk factor for esophageal carcinoma. We set out to investigate the prevalence and associated factors of high-risk HPV in formalin-fixed paraffin-embedded (FFPE) tissue blocks with esophageal carcinoma at Bugando Medical Center, a tertiary referral hospital in Mwanza, Tanzania, East Africa. METHODS: A total of 118 esophageal carcinoma FFPE tissue blocks, collected from January 2021 to December 2022, were analyzed. Genomic DNA was extracted from these tissues, and multiplex polymerase chain reaction (PCR) was performed to detect HPV using degenerate primers for the L1 region and type-specific primers for detecting HPV16, HPV18, and other high-risk HPV genotypes. Data were collected using questionnaires and factors associated with high-risk HPV genotypes were analyzed using STATA version 15 software. RESULTS: Of the 118 patients' samples investigated, the mean age was 58.3 ± 13.4 years with a range of 29-88 years. The majority of the tissue blocks were from male patients 81/118 (68.7%), and most of them were from patients residing in Mwanza region 44/118 (37.3%). Esophageal Squamous Cell Carcinoma (ESCC) was the predominant histological type 107/118 (91.0%). Almost half of the tissue blocks 63/118 (53.3%) tested positive for high-risk HPV. Among these, HPV genotype 16 (HPV16) was the most common 41/63 (65.1%), followed by HPV genotype 18 (HPV18) 15/63 (23.8%), and the rest were other high-risk HPV genotypes detected by the degenerate primers 7/63 (11.1%). The factors associated with high-risk HPV genotypes were cigarette smoking (p-value < 0.001) and alcohol consumption (p-value < 0.001). CONCLUSION: A substantial number of esophageal carcinomas from Bugando Medical Center in Tanzania tested positive for HPV, with HPV genotype 16 being the most prevalent. This study also revealed a significant association between HPV status and cigarette smoking and alcohol consumption. These findings provide important insights into the role of high-risk HPV in esophageal carcinoma in this region.

Epidemiology and genotypes analysis of human papillomavirus infection in Beijing, China.

BACKGROUND: This study aimed to investigate the epidemiology of high-risk human papillomavirus (HPV) in the female population in Beijing, China, and identify the relationship between HPV genotypes and host factors. METHODS: HPV testing was performed on women aged 15-89 (mean age 38.0 ± 10.9 years) from Beijing in 2020. High-risk HPV genotyping real-time polymerase chain reaction was used to determine HPV genotypes. The overall prevalence, age-specific prevalence, genotype distribution, and the correlation between HPV genotypes and cervical cytology were analyzed. RESULTS: Among the 25,344 study participants, the single and double infection rates were 18.8% (4,777/25,344) and 4.2% (1,072/25,344), respectively. A total of 6,119 HPV-positive individuals were found to have 91.6% negative results for intraepithelial lesion or malignancy (NILM), 5.8% atypical squamous cells of undetermined significance (ASC-US), 0.9% low-grade squamous intraepithelial lesion (LSIL), and 1.7% high-grade squamous intraepithelial lesion (HSIL). In single HPV infections, the HPV16 genotype was highly associated with cervical cytology severity (χ2 trend = 172.487, P < 0.001). Additionally, HPV infection rates increased gradually with age, and statistical differences were observed across age groups (χ2 = 180.575; P < 0.001). High-risk HPV genotypes were highly prevalent in women below 25 years of age and those aged 55-59 years. Cluster analysis revealed that the 13 HPV genotypes could be roughly divided into two groups in a single infection; however, patterns of infection consistent with biological characteristics were not observed. CONCLUSION: High-risk HPV was found in 24.1% of outpatients, with HPV52, HPV58, HPV16, HPV39, and HPV51 being the most common high-risk genotypes. Single high-risk HPV infection was predominant. HPV16, HPV39, HPV51, and HPV52 were associated with cervical lesion progression. HPV16 infection was especially worrying since it aggravates cervical lesions. Because the infection rates of the 13 HPV genotypes differed by age, the peak HPV infection rate should not guide vaccination, screening, and prevention programs. Instead, these initiatives should be tailored based on the regional HPV distribution characteristics. Moreover, it was determined that Beijing's populace needed to receive treatment for HPV39 infection.

High-risk human papillomavirus diversity among indigenous women of western Botswana with normal cervical cytology and dysplasia.

BACKGROUND: Cervical cancer remains a public health problem despite heavy global investment in health systems especially in low-and-middle-income countries (LMIC). Prophylactic vaccines against the most commonly detected human papillomavirus (HPV) types in cervical cancers are available and decisions on the selection of vaccine design depends on the prevalence of high-risk (hr) HPV genotypes for a particular region. In 2015, Botswana adopted the use of a quadrivalent HPV vaccine as a primary prevention strategy. Secondary prevention includes cervical smear screening whose uptake remains notably low among indigenous and marginalized communities despite efforts to improve access. AIM: To determine the prevalence of hrHPV genotypes and cervical lesions' burden in women from the indigenous and marginalized communities of Botswana. METHODS: This prospective survey enrolled 171 non-HPV vaccinated women aged 21 years and older. Face-to-face interviews, Pap smear screening, hr-HPV and Human Immuno-deficiency virus (HIV) testing were carried out. Conventional Papanicolau smears were analyzed and cervical brushes were preserved for hrHPV testing using the Ampfire Multiplex HR-HPV protocol which detects the following genotypes: HPV 16, 18, 31, 35, 39, 45, 51, 52, 53, 56, 58, 59 and 68. RESULTS: In this study, 168/171 (98.6%) of the women consented to HIV testing; 53/171 (31%) were living with HIV and self-reported enrolment on antiretroviral therapy. Among the women examined, 23/171 (13.5%) had cervical dysplasia with most presenting with Atypical Squamous Cells of Undetermined Significance 8/23 (35%), Low-Grade Squamous Intraepithelial Lesions 8/23 (35%), Atypical Squamous Cells-High Grade 4/23 (17%), Atypical Endocervical Cells 2/23 (9%) and Atypical Endocervical Cell favoring neoplasia 1/23(4%). However, no High-Grade Squamous Intraepithelial Lesions (HSIL) or squamous cell carcinoma (SCC) were detected. Overall hrHPV prevalence in this study was at 56/171 (32.7%). The most commonly detected hrHPV genotypes in women with cervical dysplasia were HPV39 (6.25%), HPV51 (14.5%), HPV52 (12.5%) and HPV56 (4%). Notably, HPV 16 and 18 were not found in women with cervical dysplasia. CONCLUSIONS: Our study provides valuable insights into the prevalence and distribution of hrHPV genotypes in indigenous and marginalized communities in Botswana, and the need for further investigation of their potential role in cervical carcinogenesis in this population. These results may also serve as baseline data to facilitate future evaluation of the HPV vaccine needs.

HPV specificity and multiple infections and association with cervical cytology in Chongqing, China: a cross-sectional study.

BACKGROUND: It is important to assess the relationship between specific HPV genotype or multiple infection and cervical cytology. The protection provided by the HPV vaccine is type-specific, and the epidemiology feature of coinfections needs to be investigated. The aim is to provide baseline information for developing HPV vaccination and management of HPV-positive populations in the region. METHODS: A total of 3649 HPV-positive women were collected from 25,572 women who underwent 15 HR-HPV genotypes and ThinPrep cytologic test (TCT) results. Logistic regression was used to determine the correlation between the risk of cytology abnormalities and specific HPV infection. We calculated odds ratios (ORs) to assess coinfection patterns for the common two-type HPV infections. chi-squared test was used to estimate the relationship between single or multiple HPV (divided into species groups) infection and cytology results. RESULTS: The results showed there was a positive correlation between HPV16 (OR = 4.742; 95% CI 3.063-7.342) and HPV33 (OR = 4.361; 95% CI 2.307-8.243) infection and HSIL positive. There was a positive correlation between HPV66 (OR = 2.445; 95% CI 1.579-3.787), HPV51 (OR = 1.651; 95% CI 1.086-2.510) and HPV58(OR = 1.661; 95% CI 1.166-2.366) infection and LSIL. Multiple HPV infections with α9 species (OR = 1.995; 95% CI 1.101-3.616) were associated with a higher risk of high-grade intraepithelial lesions (HSIL) compared with single HPV infection. There were positive correlations between HPV66 and HPV56 (α6) (OR = 3.321; 95% CI 2.329-4.735) and HPV39 and HPV68 (α7). (OR = 1.677; 95% CI 1.127-2.495). There were negative correlations between HPV52, 58, 16 and the other HPV gene subtypes. CONCLUSION: HPV33 may be equally managed with HPV16. The management of multiple infections with α9 may be strengthened. The 9-valent vaccine may provide better protection for the population in Chongqing currently. The development of future vaccines against HPV51 and HPV66 may be considered in this region.

Understanding the HPV associated cancers: A comprehensive review.

Human papillomavirus (HPV), a common cause of sexually transmitted diseases, may cause warts and lead to various types of cancers, which makes it important to understand the risk factors associated with it. HPV is the leading risk factor and plays a crucial role in the progression of cervical cancer. Viral oncoproteins E6 and E7 play a pivotal role in this process. Beyond cervical cancer, HPV-associated cancers of the mouth and throat are also increasing. HPV can also contribute to other malignancies like penile, vulvar, and vaginal cancers. Emerging evidence links HPV to these cancers. Research on the oncogenic effect of HPV is still ongoing and explorations of screening techniques, vaccination, immunotherapy and targeted therapeutics are all in progress. The present review offers valuable insight into the current understanding of the role of HPV in cancer and its potential implications for treatment and prevention in the future.

The application value of low-risk human papillomavirus testing in cervical cancer prevention and treatment in low- and middle-resource areas.

OBJECTIVES: To assess the application value of low-risk human papillomavirus (lrHPV) detection in the prevention and treatment of cervical cancer in low- and middle-resource areas (LMRAs). STUDY DESIGN: A retrospective cross-sectional study. METHODS: Cervical HPV typing results were collected from 2019 to 2023, utilizing fluorescence PCR technology. An adjusted logistic regression model was used to assess the relative risk (OR) and 95 % confidence interval (CI) for co-infection with lrHPV and high-risk HPV (hrHPV). RESULTS: Out of 113,883 women included in the study, the overall lrHPV positivity rate was 1.9 %. In total, 47.7 % (1033/2167) of lrHPV positive women also had hrHPV co-infections. Multivariate analysis identified 12 hrHPV subtypes (T-hrHPV) significantly associated with co-infection risk, including HPV16, 31, 33, 39, 51, 52, 53, 56, 59, 66, 68, and 73. The risk of T-hrHPV infection was 3.77 times higher (95 % CI: 3.44-4.12) for women with a single lrHPV infection and 9.71 times higher (95 % CI: 4.72-19.99) for those with two lrHPV infections. Women screened in the gynecological outpatient clinic faced a T-hrHPV infection risk 2.64 times higher (95 % CI: 2.54-2.74) than those in the general health check department. CONCLUSIONS: lrHPV positivity significantly increases the risk of T-hrHPV co-infection, particularly under multiple infections, highlighting the importance of comprehensive HPV screening in LMRAs. The notable differences in T-hrHPV infection risks across various screening settings highlight their critical role in cervical cancer prevention and offer new insights into optimizing vaccination strategies to enhance effective prevention and treatment in LMRAs.

Retrospective analysis of negative cytology results correlated with a positive high-risk in the human papillomavirus result and subsequent results of patients over a period of three years.

This research paper evaluates the efficacy of co-testing in precluding cervical cancer, with a particular focus on distinguishable outcomes of the human papillomavirus (HPV) vs. cytology tests. A retrospective review of 5948 patients, who tested positive for high-risk HPV but showed negative cytologic findings, revealed that 15.006% tested positive in subsequent screenings. A comparative analysis of various commercial HPV tests highlighted the precision of mRNA-based HPV testing by Aptima (Hologic) in reducing the likelihood of false-negative cytology. The paper challenges the conviction that a negative cytology alone suffices advocating for a condensed testing interval in instances of positive HPV outcomes, thereby facilitating earlier intervention and optimal preventive care. These findings unveil an exigency for reconsidering preventive strategies based on test outcomes.

High-Risk HPV CISH Detection in Cervical Biopsies with Weak and/or Focal p16 Immunohistochemical Positivity.

In cervical biopsies, for diagnosis of Human Papilloma Virus (HPV) related conditions, the immunohistochemical staining for p16 has a diagnostic value only if diffusely and strongly positive, pattern named "block-like". "Weak and/or focal (w/f) p16 expression" is commonly considered nonspecific. In our previous study, we demonstrated the presence of high-risk HPV (hrHPV) DNA by LiPa method in biopsies showing w/f p16 positivity. The aim of the present study was to investigate the presence of hrHPV-DNA by CISH in the areas showing w/f p16 expression. We assessed the presence of hrHPV16, 18, 31, 33, 51 by CISH in a group of 20 cervical biopsies showing w/f p16 expression, some with increased Ki67, and in 10 cases of block-like expression, employed as control. The immunohistochemical p16 expression was also assessed by digital pathology. hrHPV-CISH nuclear positivity was encountered in 12/20 cases of w/f p16 expression (60%). Different patterns of nuclear positivity were identified, classified as punctate, diffuse and mixed, with different epithelial distributions. Our results, albeit in a limited casuistry, show the presence of HPV in an integrated status highlighted by CISH in w/f p16 positive cases. This could suggest the necessity of a careful follow-up of the patients with "weak" and/or "focal" immunohistochemical patterns of p16, mainly in cases of increased Ki67 cell proliferation index, supplemented with molecular biology examinations.

The vaginal microbiota of women living with HIV on suppressive antiretroviral therapy and its relation to high-risk human papillomavirus infection.

BACKGROUND: Few studies have investigated the vaginal microbiota (VM) in women living with HIV (WLWH) in the context of high-risk human papillomavirus (HR-HPV) infection, even though WLWH are at an increased risk of HPV-related malignancies, including cervical cancer. To explore the impact of HIV and HPV infection on the VM in WLWH, we determined the prevalence of HR-HPV infection and cervical cytologic abnormalities in a cohort of 44 WLWH and 39 seronegative-women (SNW), characterized the vaginal microbiota by 16S sequencing, assessed genital inflammation and systemic immune activation by multiplex bead assay and flow cytometry, respectively. Finally, we explored relationships between bacterial richness and diversity, the top 20 bacterial genera, genital inflammation and systemic immune activation. RESULTS: We found that HR-HPV prevalence was similar between WLWH and SNW. High-grade squamous intraepithelial lesions (HSIL) were only detected in WLWH negative for HR-HPV infection. In regression analyses, no risk factors were identified. Women co-infected with HIV and HR-HPV had the highest level of systemic immune activation, and these levels were significantly different compared with SNW without HR-HPV infection. Lactobacillus iners was the dominant Lactobacillus species in WLWH and SNW alike. CONCLUSION: We found no evidence of differences in vaginal microbial richness and diversity, microbial community structure, and genital inflammation by HIV, HPV, or HIV and HPV status.

Characteristics of high-risk HPV infection in women with vaginal intraepithelial neoplasia in Beijing, China.

We evaluated the characteristics of high-risk human papillomavirus (Hr-HPV) infection in different grades of vaginal intraepithelial neoplasia (VaIN). 7469 participants were involved in this study, of which 601 were diagnosed with VaIN, including single vaginal intraepithelial neoplasia (s-VaIN, n = 369) and VaIN+CIN (n = 232), 3414 with single cervical intraepithelial neoplasia (s-CIN), 3446 with cervicitis or vaginitis and 8 with vaginal cancer. We got those results. First, the most popular HPV genotypes in VaIN were HPV16, 52, 58, 51, and 56. Second, our study showed that higher parity and older age were risk factors for VaIN3 (p < 0.005). Third, the median Hr-HPV load of VaIN+CIN (725) was higher than that of s-CIN (258) (p = 0.027), and the median Hr-HPV load increased with the grade of VaIN. In addition, the risk of VaIN3 was higher in women with single HPV16 infections (p = 0.01), but those with multiple HPV16 infections faced a higher risk of s-VaIN (p = 0.003) or VaIN+CIN (p = 0.01). Our results suggested that women with higher gravidity and parity, higher Hr-HPV load, multiple HPV16 infections, and perimenopause or menopause status faced a higher risk for VaIN, while those with higher parity, single HPV16 infections, and menopause status are more prone to VaIN3.

p16/Ki67 dual stain triage versus cytology in primary human papillomavirus-based cervical cancer screening with limited genotyping.

The introduction of primary human papillomavirus (HPV) cervical cancer screening requires the implementation of an appropriate triage strategy that will be effective in detecting high-grade cervical disease without losing diagnostic specificity. From the 30.066 screening tests results, a total of 1086 with available high-risk human papillomavirus (HRHPV) with limited genotyping, cytology, and p16/Ki67 dual-stain were selected. Two triage strategies for primary HPV screening were analyzed retrospectively based on the study group. Performance characteristics for p16/Ki67 and cytology triage in the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+) were calculated, detected in colposcopic biopsy. In HPV16/18-positive cases, primary HPV with p16/Ki67 triage was significantly more specific than cytology (53.1%/16.8% for CIN2+; p < 0.0001; 45.9%/17.0% for CIN3+; p < 0.0001), with yielded sensitivity (95.7%/84.8% for CIN2+; p = 0.0955; 100.0%/87.5% for CIN3+; p = 0.0832). In other HRHPV-positive cases (N16/N18), p16/Ki67 triage was also significantly higher specific (51.3%/15.3% for CIN2+; p < 0.0001; 44.5%/16.5% for CIN3+; p < 0.0001), with sensitivity (92.3%/74.4% for CIN2+; p = 0.0522; 90.9%/81.8% for CIN3+; p = 0.5637). Diagnostic predictive values were significantly higher for p16/Ki67 triage with the highest PPV in HPV16/18-positive cases for CIN2+ (45.4%; 95% confidence interval [CI]: 35.2-55.8; p < 0.0001) and very high NPV in all HPV-positive cases regardless of detected genotype (96.3%-100.0%). The risk (1-NPV) for CIN3+ in HRHPV16/18-positive/p16/Ki67-negative women was 0.0%. Superior diagnostic performance compared to cytology for detecting cervical cancer precursors indicates that p16/Ki67 dual-immunostain may be a highly effective tool of triage in primary HPV screening with limited HPV 16/18 genotyping in secondary cervical cancer prevention.

Vaginal microbiome community state types and high-risk human papillomaviruses in cervical precancer and cancer in North-central Nigeria.

BACKGROUND: High risk human papillomaviruses (HR-HPV) have a causal role in cervical oncogenesis, and HIV-mediated immune suppression allows HR-HPV to persist. We studied whether vaginal microbiome community state types (CSTs) are associated with high-grade precancer and/or invasive cervical cancer (HSIL/ICC). METHODS: This was a cross-sectional study of adult women with cervical cancer screening (CCS) at the Jos University Teaching Hospital (JUTH) in Jos, Nigeria, between January 2020 and February 2022. Cervical swabs underwent HPV genotyping (Anyplex™ II HPV28). Cervico-vaginal lavage (CVL) sample was collected for 16 S rRNA gene amplicon sequencing. We used multivariable logistic regression modelling to assess associations between CSTs and other factors associated with HSIL/ICC. RESULTS: We enrolled 155 eligible participants, 151 with microbiome data for this analysis. Women were median age 52 (IQR:43-58), 47.7% HIV positive, and 58.1% with HSIL/ICC. Of the 138 with HPV data, 40.6% were negative for HPV, 10.1% had low-risk HPV, 26.8% had single HR-HPV, and 22.5% had multiple HR-HPV types. The overall prevalence of any HR-HPV type (single and multiple) was 49.3%, with a higher proportion in women with HSIL/ICC (NILM 31.6%, LSIL 46.5%, HSIL 40.8%, and 81.5% ICC; p = 0.007). Women with HIV were more likely to have HSIL/ICC (70.3% vs. 29.7% among women without HIV). In crude and multivariable analysis CST was not associated with cervical pathology (CST-III aOR = 1.13, CST-IV aOR = 1.31). However, in the presence of HR-HPV CST-III (aOR = 6.7) and CST-IV (aOR = 3.6) showed positive association with HSIL/ICC. CONCLUSION: Vaginal microbiome CSTs were not significantly associated with HSIL/ICC. Our findings suggest however, that CST could be helpful in identifying women with HSIL/ICC and particularly those with HR-HPV. Characterization of CSTs using point-of-care molecular testing in women with HR-HPV should be studied as an approach to improve early detection and cervical cancer prevention. Future longitudinal research will improve our understanding of the temporal effect of non-optimal CST, HR-HPV, and other factors in cervical cancer development, prevention, and control.

Factors associated with failed 'test of cure' in the NHS Cervical Screening Programme: A retrospective cohort study.

OBJECTIVE: To determine predictive factors associated with failed 'test of cure' (TOC) in the NHS Cervical Screening Programme (NHSCSP). METHODS: Retrospective cohort study of all patients treated by large loop excision of transformation zone (LLETZ) between 1st April 2014 and 1st April 2019. Those with no documented HPV genotype on referral, no TOC outcome, those having a hysterectomy, chemotherapy and/or radiotherapy were excluded from final analysis. RESULTS: Patients referred with a singular HPV genotype of HPV 16, HPV 18, or HPV Other types (HPV O) were significantly more likely to pass TOC than those referred with multiple HPV genotypes (p < 0.0001). Those with HPV genotypes including HPV O were significantly more likely to fail TOC as compared to those with genotypes of solely HPV 16 and/or 18 (p < 0.0001). Patients aged ≥51 years were significantly more likely to fail TOC when compared to all other age groups (p < 0.0001). CONCLUSION: Age >51 yrs. and infection with multiple hr-HPV types were predictors of post treatment hr-HPV persistence. Knowledge of HPV genotype both at referral, and following treatment, could allow a more individualised, and patient-centred, approach to both the management and follow up of CIN. HPV genotype should be reported as standard on all cervical screening sample results. The term HPV O should not be utilised and instead actual HPV genotype should be reported. This would enable us to optimise not only future research but would also allow future monitoring of the efficacy of vaccination programmes.

Effectiveness of quadrivalent HPV vaccination in reducing vaccine-type and nonvaccine-type high risk HPV infection.

This study aimed to assess human papillomavirus (HPV) vaccine effectiveness (VE) against both vaccine-type and nonvaccine-type high-risk HPV (hrHPV) infection, and duration of protection in United States. The study population was female participants aged 18-35 years with an HPV vaccination history and genital testing for HPV from the National Health and Nutrition Examination Survey, 2007-2016. Participants vaccinated before sexual debut were assessed against 13 nonvaccine-type hrHPV infection including 31/33/35/39/45/51/52/56/58/59/68/73/82. Multivariable logistic regression was used to estimate VE overall, by age at diagnosis, time since vaccination and lifetime sexual partners. A total of 3866 women were included in the analysis, with 23.3% (95% CI 21.3%-25.4%) having been vaccinated (≥1 dose). VE against vaccine-type HPV18/16/11/6 infection was 58% overall, which was mainly driven by those aged 18-22 years (VE = 64%) and 23-27 years (65%). Among participants aged 18-22 years vaccinated before sexual debut, the VE was 47% (23%-64%) against 13 nonvaccine-type hrHPV and 61% (95% CI 36%-77%) against 5 selected nonvaccine-type hrHPV35/39/52/58/59. Both direct effectiveness and cross-protection maintained effective for 5-10 years post vaccination. We also found the prevalence of ever diagnosed cervical cancer among vaccinated was significantly lower (0.46%, 4/874) than that among unvaccinated participants (1.27%, 38/2992). These findings highlight the potential of significant reduction of cervical cancer following the universal HPV vaccination programme.

Prevalence and genotype screening of human papillomavirus among women attending a private hospital in Northern Cyprus: an 11-year retrospective study.

BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted pathogen both in men and women. Accumulating epidemiological evidence supports a strong association between HPV infection and cancer of the cervix, vulva, vagina, anus, and penis. Currently, data on the HPV prevalence and genotyping is lacking in Northern Cyprus, a region in which HPV vaccination is not freely accessible via the national immunization program. The aim of this study was to evaluate the HPV type-specific prevalence in women with and without cytological abnormalities living in Northern Cyprus. METHODS: A total of 885 women who presented to the Department of Gynecology and Obstetrics Clinic between January 2011 and December 2022 were included in the study. Samples were collected for cytology. Cervical specimens were investigated for the presence of HPV-DNA and genotyping of HPV was performed using real-time polymerase chain reaction (rtPCR). Cytological examination was interpreted according to the Bethesda system. RESULTS: Among all patients, overall high-risk HPV DNA prevalence was 44.3%. HPV-16 and HPV-18 positivity was found in 10.4% and 3.7% of women respectively, while other high-risk HPV (OHR-HPV) was the most frequent type of HPV (30.2%). The highest frequency of HPV infection was observed in the 30-55 age group (51.0%), followed by the < 30 age group (45.7%). Co-infection with two or more HPV types was observed in 17.0% of all positive samples, in which the prevalence of HPV-16 + HPV-18 was 2.3%, HPV-16 + OHR-HPV and HPV-18 + OHR-HPV was 12.0% and 5.1%, respectively. Among the screened patients, 37.5% had abnormal and 62.5% had normal cytology results. HR-HPV positivity was 65.7% and 34.0% in patients with abnormal and normal cytology. The highest incidence of HRC-HPV was OHR-HPV types (44.7%) in positive cytology cases. Among women with a cytology result of ASCUS, L-SIL, H-SIL and unspecified dysplasia, 52.1%, 67.6%, 97.5% and 75.6% were respectively infected with HR-HPV. CONCLUSION: The present study provides the latest epidemiological data related to HPV prevalence and genotype distribution among women living in Northern Cyprus. Considering the unavailability of free vaccination in the community, it is imperative to implement local HPV screening programs and provide guidelines on HPV prevention and measures during early school education.

Cervical human papillomavirus prevalence according to socioeconomic and demographic characteristics in a large Danish screening population.

AIM: The aim of this study was to investigate high-risk human papillomavirus (hrHPV) prevalence according to socioeconomic and demographic characteristics in a Danish screening population. METHODS: We used data from HPV SCREEN DENMARK, which was an implementation study embedded into the routine cervical cancer screening programme. During 2017-2020, women aged 30-59 years screened in the Region of Southern Denmark were offered HPV testing or cytology. In the HPV group, liquid-based cytology samples were tested for 14 hrHPV types. We obtained registry information on socioeconomic and demographic characteristics and used log-binomial regression to estimate the prevalence ratio (PR) of hrHPV in three age groups (30-39, 40-49, 50-59 years), adjusting for age and marital status. RESULTS: We included 31,124 HPV unvaccinated women. In all age groups, the age-adjusted hrHPV prevalence was higher in women with basic versus higher education (e.g. age 30-39: 11.9% vs. 9.5%; PRage-adjusted=1.24; 95% confidence interval (CI): 1.02-1.50); women who were unemployed vs. employed (e.g. age 30-39: 11.6% vs. 10.4%; PRage-adjusted=1.11; 95% CI: 0.95-1.28); and in women with highest vs. lowest income (e.g. age 30-39: 11.6% vs. 9.5%, PRage-adjusted=1.18, 95% CI: 0.98-1.44). In models adjusted for marital status, these associations largely disappeared. CONCLUSIONS: We found slightly higher hrHPV prevalences in women with basic education, low income and unemployment. The differences largely disappeared when taking into account marital status as a potential proxy for sexual behaviour. Our findings support a need for targeted information on safe sexual practices and promoting socioeconomic equality in HPV vaccination and cervical cancer screening participation.

Are HPV-negative lesions concerned for the introduction of primary HPV testing for cervical cancer screening in Japan?

AIM: In Japan, primary human papilloma virus (HPV) testing has not been introduced for cervical cancer screening due to concerns that HPV-negative lesions may be missed and a lack of Japanese data. The purpose of this study was to evaluate the validity of primary HPV testing in Japan by analyzing cervical intraepithelial neoplasia 2 (CIN2) or more/high-risk HPV- (CIN2+/hrHPV-) cases in cervical cancer screening. METHODS: Data from 35 525 cervical cancer screenings with HPV testing and cervical cytology from 2011 to 2019 in Saga City, Japan, were reviewed. The cases with low-grade squamous intraepithelial lesion (LSIL+)/hrHPV- were analyzed in detail. RESULTS: The results of the 35 525 examinees were as follows: 31 123 were negative for intraepithelial lesion or malignancy (NILM)/hrHPV-, 2612 were NILM/hrHPV+, 262 were atypical squamous cells of undetermined significance (ASC-US)/hrHPV-, 213 were ASC-US/hrHPV+, 291 were LSIL+/hrHPV-, and 1024 were LSIL+/hrHPV+. Of the 256 LSIL+/hrHPV- examinees for whom histology was available, CIN2+ were CIN2 9.4% (24/256), CIN3 3.9% (10/256), cervical adenocarcinoma 0.4% (1/256), uterine corpus cancer 1.2% (3/256), and uterine sarcoma 0.4% (1/256). Overall, the rate of LSIL+/hrHPV- was 0.82% (291/35.525), 0.1% (36/35525) of which were cervical lesions with CIN2+. Only one cervical adenocarcinoma was detected, but gastric-type adenocarcinoma was not included. CONCLUSION: HPV-negative CIN2+ or cervical adenocarcinoma is not a concern for the introduction of primary HPV screening in Japan. Primary HPV testing in cervical cancer screening is considered a feasible method that can be used in Japan, although an algorithm suitable for Japan and a national-level management system need to be established.