Cervical cancer risk and high-risk HPV types distribution in Saudi Arabia: Trends from a national laboratory-based study

To investigate the epidemiology of human papillomavirus (HPV) infection in Malian women, for whom cervical cancer is the most common cancer and the second most common cause of cancer-related mortality. Pilot study of 202 women aged 15-65 to determine the prevalence rate of high-risk HPV infection among unscreened Malian women. Information on risk factors was collected through a standardized, structured interview and clinical examination. High-risk (HR) HPV DNA was detected using signal amplification methods (hybrid capture II). High-risk HPV DNA was detected in 12% of unscreened women, while visual inspection after application of acetic acid and Lugol's iodine (VIA/VILI) identified suspicious abnormalities in 2.5% of unscreened women. Histopathological evaluation of VIA/VILI-positive biopsies revealed no evidence of cervical intraepithelial neoplasia or cervical cancer. The majority of infections occurred among women in the 15-24 year old range. Compared to women who were married or widowed, single women were 3.5 times more likely to be infected with HR HPV. The prevalence of infection with cancer causing types of HPV in this study was 12%. These prevalence estimates are consistent with what has been reported previously for other West African countries.

Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and it is responsible for most cases of cervical uterine cancer. Although HPV infections of the cervix do not always progress to cancer, 90% of cervical cancer cases have been found to be associated with high risk HPV (HR- HPV) infection. HPV DNA testing is widely used, along with Papanicolaou (Pap) testing, to screen for cervical abnormalities. However, there are no data on the prevalence of genotype-specific HPV infections assessed by measuring HPV E6/E7 mRNA in women representative of the Chinese population across a broad age range. In the present study, we compared the results with the CervicGen HPV RT-qDx assay, which detects 16 HR-HPV genotypes (Alpha-9: HPV 16, 31, 33, 35, 52, and 58; Alpha-7: HPV 18, 39, 45, 51, 59, and 68; and Alpha-5, 6: HPV 53, 56, 66, and 69), and the REBA HPV-ID assay, which detects 32 HPV genotypes based on the reverse blot hybridization assay (REBA) for the detection of oncogenic HPV infection according to cytological diagnosis. We also investigated the prevalence and genotype distribution of HPV infection with a total of 324 liquid-based cytology samples collected in western Shandong province, East China. The overall HPV prevalences determined by HPV DNA and HPV E6/E7 mRNA assays in this study were 79.9% (259/324) and 55.6% (180/324), respectively. Although the positivity of HPV E6/E7 mRNA expression was significantly lower than HPV DNA positivity, the HPV E6/E7 mRNA assay showed greater specificity than the HPV DNA assay (88.6% vs. 48.1%) in normal cytology samples. The prevalence of Alpha-9 (HPV 16, 31, 33, 35, 52, and 58) HPV infection among these women accounted for up to 80.3% and 76.1% of the high-grade lesions detected in the HPV mRNA and DNA tests, respectively. The HR-HPV genotype distribution, based on HPV DNA and E6/E7 mRNA expression by age group in patients with cytologically confirmed lesions, was highest in women aged 40 to 49 years (35.9% for cytologically confirmed cases, Pearson correlation r value=0.993, p<0.001) for high-grade lesions. Among the oncogenic HR-HPV genotypes for all age groups, there was little difference in the distribution of HPV genotypes between the HPV DNA (HPV -16, 53, 18, 58, and 33) and HPV E6/E7 mRNA (HPV -16, 53, 33, 58, and 18) assays. HPV 16 was the most common HPV genotype among women with high- grade lesions. Our results suggest that the HPV E6/E7 mRNA assay can be a sensitive and specific tool for the screening and investigation of cervical cancer. Furthermore, it may provide useful information regarding the necessity for early cervical cancer screenings and the development of additional effective HPV vaccines, such as one for HPV 53 and 58. Additionally, gaining knowledge of HPV distribution may also inform us about ecological changes in HPV after the vaccination.

Background: Human papillomavirus (HPV) infection is a major cause of cervical cancer and premalignant dysplasia. The prevalence and distribution of different high-risk HPV genotypes can affect HPV vaccination strategies and the design of cervical cancer prevention programs. Objective: Here, we aimed to determine the prevalence of different HPV genotypes in women with abnormal Cervical cytology in the United Arab Emirates (UAE), evaluate correlations between HPV genotypes and the degree of cervical dysplasia, and observe distributions of HPV genotypes across age groups. Methods: The study included 442 women who underwent HPV genotyping at our institution between January 2018 and September 2019. A retrospective chart review was conducted for all 442 cases, and data were collected from hospital records. Results: The overall HPV positivity rate was 56.1%. The prevalence of high-risk HPV was 48%; 35.4% of patients had multiple high-risk HPV strains, whereas 64.6% had a single high-risk HPV strain. The most common high-risk HPV genotype was HPV-16 (15.2%), followed by HPV-31 (11.7%), HPV-53 (8.9%), HPV-66 (8.6%), and HPV-51 (8.3%). The prevalence of HPV-18 was only 3.8%. The high-risk HPV positivity rate Increased from 39% in women with Atypical Squamous Cells of Undetermined Significance (ASCUS) to 81% in women with Low-grade Squamous Intraepithelial Lesions (LSILs), 81.3% in women with atypical squamous cells cannot rule out High-Frade Lesions, and 80% in women with High-Grade Squamous Intraepithelial Lesions (HSILs). The multiple high-risk HPV strain positivity rate increased from 32.4% in ASCUS to 44.7% in LSIL and 62.5% in HSIL. Increased HPV positivity rates and prevalence of HPV-16 were noted with increasing severity of cervical dysplasia. Decreased HPV positivity was observed with increasing age. Conclusion: Overall, because the prevalence and distribution of different high-risk HPV genotypes affect HPV vaccination strategies, our findings may be useful for the design of cervical cancer prevention programs.

A retrospective analysis of human papillomavirus (HPV) prevalence and genotype distribution among 25,238 women in Shanghai, China revealed the limitations of current HPV-based screening and HPV vaccine

Objective To investigate the incidence of human papillomavirus (HPV) infection and the distribution of HPV subtypes in women for physical examination in Anhui area, and to provide evidence for the prevention and treatment of cervical cancer. Methods The sample of female cervical exfoliated cells specimen were collected by Hefei KingMed Diagnostics laboratory and HPV genotypes were detected by polymerase chain reaction reverse dot blot hybridization (PCR-RDB) method. According to the genotype results, the potential infection rate and HPV subtypes, the detection rate of each genotype and the distribution of different age groups were analyzed, respectively. Results Among the 17 160 samples from healthy women for physical examination, a total of 2 990 cases were HPV positive, with the positive rate 17.42% (2 990/ 17 160). Seventeen high-risk genotypes and 6 low-risk genotypes of HPV were all detected. Cases with single genotype HPV infection accounted for 73.71% (2 204/2 990), double HPV genotypes infection were 19.03% (569/2 990), triple HPV genotypes were 5.55% (166/2 990); while quadruple HPV genotypes (43 cases), five genotypes (7 cases) and six genotypes (1 case) infection accounted for 1.71% (51/2 990) in total. Among the 2 204 cases with single genotype HPV infection, 1 829 (82.99%) cases were with high-risk genotypes HPV infection. The common high-risk subtypes were HPV52 (20.07%, 367/1 829), HPV16 (16.84%, 308/ 1 829), HPV53 (9.84%, 180/18 29) and HPV18 (8.26%, 151/1 829). The detection rate of the above four high-risk genotypes of HPV accounted for 55.00%, relative to the total high-risk genotype of HPV infection (1 006/1 829). The remaining 823 patients were distributed in the other 13 high-risk genotypes of HPV. There were 375 cases with low-risk genotype of HPV infection, the most common of which was HPV81 (40.00%, 150/375), followed by HPV42 (22.13%, 83/375) and HPV43 (17.33%, 65/375). The other 23 patients were distributed in the other 3 middle and low risk genotypes. Among the cases with double HPV infection, 390 cases (68.54%) were with only high-risk HPV subtypes infection, 10 cases (1.76%) with only low-risk HPV subtypes infection and 169 cases (29.70%) with high-risk and low-risk HPV subtypes mixed infection. Among the triple HPV genotypes infection, 73 cases (43.98%) were with only high-risk HPV subtypes infection, 2 cases (1.20%) were with only low-risk HPV subtypes infection and 91 cases (54.82%) with high-risk and low-risk HPV subtypes mixed infection. Among quadruple and above HPV genotypes infection, 22 cases (43.14%) were with only high-risk subtypes HPV infection, no case was with only low-risk HPV subtype infection and 29 cases (56.86%) with high-risk and low-risk HPV subtypes mixed infection. High-risk HPV subtype infection was the main infection, whether in single HPV subtype infection or in multiple HPV subtypes infection. The positive rates of HPV in groups aged 21-25, 26-30, 31-35, 36-40, 41-45, 46-50 ,51-55, 56-60 and ≥ 61 years old were significantly different (χ2 = 28.701, P < 0.001). Conclusions HPV infection in healthy women in Anhui was maily single subtype infection and high-risk subtypes infection, and the high-risk infection rate ranks HPV52, HPV16, HPV53 and HPV18, and the infection rate of different age groups were significantly different. Key words: Human papillomavirus; Genotype; Physical examination; Women; Cervical cancer

Editor's evaluation: Approximating missing epidemiological data for cervical cancer through Footprinting: A case study in India

Decision letter: Approximating missing epidemiological data for cervical cancer through Footprinting: A case study in India

Correlation of high-risk human papilloma viruses but not of herpes viruses or Chlamydia trachomatis with endometriosis lesions

BackgroundWomen living with HIV are at risk for cervical dysplasia and cancer worldwide. In 2015, the World Health Organization (WHO) recommended that testing for high-risk HPV (hrHPV) infection be incorporated into cervical cancer screening programs using molecular nucleic acid tests (NATs) but this has not previously been done in Uganda. The country’s coverage for Human Papilloma Virus (HPV) screening remains low at less than 10% for women aged 25–49 years. This study determined the genital prevalence of hrHPV infection and the associated factors among women living with HIV in Uganda.MethodsA descriptive cross-sectional study was conducted in 15 selected health facilities among participants who were on Antiretroviral therapy (ART). Participants who consented to participate were instructed on how to collect their own high vaginal swabs using a cervical brush for HPV molecular testing (HPV DNA or HPV RNA) and their demographics data was collected using a standard questionnaire. Laboratory diagnosis for HPV molecular testing was done using Gene xpert machines and Hologic Aptima Machine. Modified Poisson regression analysis was conducted to determine the associated factors.ResultsThis study involved 5856 HIV positive participants on ART. A total of 2006 out of 5856 (34.3%) participants had high risk HPV infections. HPV infections by genotypes were: HPV16 317(15.8%), HPV 18/45 308 (15.4%) and other high-risk HPV 1381 (68.8%). The independent factors associated with all hrHPV were parity, education level, having more than one partner, and engaging in early sex. Smoking was associated with HPV 16, HPV 18/45 and other hrHPV. Age was associated with all hrHPV, marital status with HPV 16, and occupation with HPV 16.ConclusionsThe prevalence of genital high-risk HPV infections among HIV positive women attending ART clinics in public facilities in Uganda was high. Other hrHPV genotype was the commonest compared to 18/45 and HPV 16. The integration of cervical cancer screening in ART programmes remains paramount to support the early detection of cervical cancer and Non-invasive self-collected urine and vaginal sampling for cervical cancer screening present an opportunity.

Human Papilloma Virus DNA and p53 Mutation Analysis on Bladder Washes in Relation to Clinical Outcome of Bladder Cancer

Introduction: Human papillomavirus (HPV) and human immunodeficiency virus (HIV) are the most common sexually transmitted infections (STI) globally. According to the World Health Organisation (WHO) there are around 17.4 million women living with HIV and over 290 million HPV infected women worldwide.Purpose: This review is to summarize available data concerning the relationship between HIV and HPV infection among women. The analysis comprises molecular mechanisms of HPV infection among HIV(+) women as well as HIV infection among HPV(+) women, prevalence of HPV and cervical lesions among women living with HIV and screening of HPV and cervical cancer (CC) among HIV infected women.Material and methods: The review includes publications from 2011 to 2020. The data has been collected by the use of the PubMed, Ovid, Up-To-Date and WHO website. Key words used to search for references include: HPV, HIV, prevalence, molecular mechanism, screening.Results: HIV infection is a risk factor for HPV acquisition. On the one hand, prevalence of HPV, multiple HPV, high risk HPV (hrHPV) infections and cervical intraepithelial neoplasia (CIN) is higher among HIV(+) women. On the other hand, HPV infection can also predispose to HIV acquisition. Evidence on how these viruses influence each other can be a breakthrough in the range of prevention, detection and treatment of both HIV and HPV infection.Conclusions: Relationship between HPV and HIV is an interest of nowadays medicine. Possibly, these viruses may cooperate and enable infection of each other. It has been showed that the prevalence of HPV, multiple HPV, hrHPV infections and cervical lesions is higher among HIV(+) in comparison to HIV(-) women. Further studies should be performed providing an insight into a molecular mechanism responsible for this cooperation.

Cervical cancer is the most common malignant tumors in women leading to serious morbidity and mortality worldwide, especially among developing countries. A main cause of the disease is the high-risk human papillomavirus (HR-HPV) infection. HSIL usually progress to cervical cancer, and low-grade lesions, including LSIL and ASCUS, mostly turn to normal or benign lesions, but there are still a small number of patients who will progress to HSIL. Up to now there is no efficient biomarker clinically available to predict people with high risk to progress into HSIL. This study was conducted to evaluate the value of human papillomavirus (HPV) DNA, p16INK4a protein, and HPV L1 capsid protein in predicting HSIL and minimizing unnecessary colposcopy treatments. 1222 patients with HR-HPV infection or with abnormal Thinprep cytologic test (TCT) were chosen to conduct colposcopy in the cervical out-patient clinic of Shanghai First Maternity and Infant Hospital affiliated to Shanghai Tongji University from June 2014 to January 2017. TCT, cervical biopsy, HPV DNA and HPVL1 were performed on all patients. 110 patients were selected to detect p16INK4a protein. Hybrid capture 2 (HC-2) was used to detect HPV DNA, and their subgroups using gene typing system. Immunohistochemical technology was used to detect HPV L1 and p16. HPV DNA was positive in 1097 cases, with the positive rate of 89.7% (1097/1222). In particular, the positive expression rates of HPV DNA were 82.3, 95.7, 96.6 and 100% in Normal/CC, LSIL, HSIL and cervical cancer groups, respectively (p < 0.001). HPV L1 was negative in 781 cases with HR-HPV infection, and the overall negative rate is 71.1%. In patients with Normal/CC, LSIL and HSIL, the negative expression rates of HPV L1 were 91.3, 40 and 81.2%, respectively (p value < 0.001). In the 110 patients, HPV L1 was negative in 98.1% (53/54) of Normal/CC, 42.9% (12/28) of LSIL and 85.1% (23/27) of HSIL (p value = 0.0043). P16-positive rates in patients with Normal/CC, LSIL and HSIL were 33.3% (18/54), 75% (21/28) and 96.2% (26/27), respectively (p value < 0.001). 18 out of 28 cases express low positive (+) in LSIL, 25 out of 27 cases express strong positive (3+) in HSIL. Patients with L1(-)p16(+) including 18.5% (10/54) of normal/cervicitis, 60.7% (17/28) of LSIL and 85.1% (23/27) of HSIL (p value < 0.005). Furthermore, patients with L1(-)p16(1+) included 37% (10/27) of normal/cervicitis 59.3% (16/27) of LSIL and 3.7% (1/27) of HSIL; patients with L1(-)p16(2+) consisted of 0% of normal/cervicitis/LSIL and 100% (1/1) of HSIL; patients with L1(-)p16(3+) were composed of 0% of normal/cervicitis, 4.5% (1/22) of LSIL and 95.5% (21/22) of HSIL (p value < 0.005) (Table6). With the increase in the degree of the cervical lesions, the expression of HPV DNA and p16 is up-regulated while HPV L1 protein is down-regulated. HPV DNA, HPV L1 and p16 are useful markers for the prediction of HSIL. Combined detection of these three markers has important potential to predicting HSIL and minimizing unnecessary colposcope examination.

Human Papillomavirus and Vaccination

Background The epidemiology of human papilloma virus (HPV) infection and the pattern of HPV genotype distribution are much-needed parameters to assess the risk of cervical cancer among females. However, due to less availability of data on HPV burden and its genotypes from various geographical regions in India makes cervical cancer screening modalities and vaccination strategies difficult to implement. Objective The present study was conducted to identify the various genotypes particularly high-risk HPV types in premalignant or malignant cervical lesions. Methods The study was a hospital-based cross-sectional study wherein 295 symptomatic women were screened by Pap smear and multiplex real-time PCR was performed for HPV genotypes identification in women with abnormal cervical cytology. Results Out of 295 women, 237 (80.3%), 45 (15.3%), and 13 (4.4%) women had normal Pap smear, squamous cell carcinoma and precancerous cytology, respectively. Among these 58 women having abnormal cervical cytology, HPV was detected in 48 (81.0%) participants. Most common HPV genotypes in our study were HPV 16 (n = 29; 60.4%) followed by mixed infections; i.e., more than one type of HPV was detected (n = 10, 20.8%). HPV 18 was detected only in 6.25%, whereas other high-risk HPV genotypes were found to be 12.5%. Conclusion HPV positivity was >80% in women having abnormal Pap smear. The prevalence of HPV 18 was found to be much less in Central India, compared to other parts of country. HPV 16 was the most common genotype followed by mixed HPV genotype infections. It is evident from our study that symptomatic women even if having normal Pap smear should be screened for HPV and followed up with periodic Pap smears for detecting any change in cervical cytology, thus preventing cervical cancer in women.

Human papillomavirus (HPV) is considered a necessary cause of cervical cancer. The aim of the current study was to determine the burden of HPV infection among randomly sampled Danish women before the vaccine against HPV is implemented. Further we assessed the risk factor profile for prevalent high risk (HR) HPV infection and infection with multiple HR HPV types. In the present cross-sectional study, we used baseline data from a population-based cohort study where participants were interviewed and had a gynecological examination. Cervical samples were analyzed for HR HPV using Hybrid capture 2 in 10,544 women aged 20-29 years and 1443 women aged 40-50 years. Genotyping was performed using LiPA. The prevalence of HR HPV was 17.9% and 4.4% in women aged 20-29 years and 40-50 years, respectively. HPV16 was the most common HR type overall and among women with abnormal cytology. Multiple HPV types were highly prevalent, notably in the younger cohort. Lifetime number of sexual partners was the main risk factor for HR HPV infection (adj. OR = 2.8 and OR = 3.4 for > or =15 partners vs. < or =4 in respectively younger and older women), whereas number of recent sexual partners was only associated with risk in younger women. Number of partners, oral contraceptive use and self-reported chlamydia infection increased the risk of having multiple HR HPV types (compared to having a single HR HPV type). HR HPV infection was common among younger women, with HPV16 as the predominant type. We confirmed the importance of sexual activity for the risk of HR HPV infection. In addition, we found that sexual behavior also play an important role for the risk of having multiple HR HPV types.