Search

Sexually transmitted infections (STIs) have a profound impact on sexual and reproductive health worldwide. Syphilis, gonorrhea, chlamydia, and trichomoniasis are four currently curable STIs. However, most STI cases are asymptomatic and not detected without laboratory diagnostics. Hepatitis B virus, herpes simplex virus, human immunodeficiency virus (HIV), and human papillomavirus (HPV) are four viral and incurable infections, but they can be mitigated by treatment. We investigated the prevalence of selected sexually transmitted pathogens and their relationship with HPV and HIV infection in women from Maputo, the capital of Mozambique. A cross-sectional study was conducted on 233 non-pregnant women seeking health care relating to gynecological symptoms in Mavalane Health facilities in Maputo, between the 1st of February 2018 and the 30th of July 2019. Cervical brush samples were collected and DNA was extracted. Selected STIs including HPV were detected using multiplex STD and HPV Direct Flow Chip Kits through a manual Hybrispot platform (Vitro, Master Diagnostica, Sevilla, Spain). HIV testing was performed using rapid tests: Determine HIV 1/2 test (Alere Abbott Laboratories, Tokyo, Japan) for screening, and UniGold HIV (Trinity Biotech, Ireland) for confirmation. All women (n = 233) were negative for Haemophilus ducreyi and Herpes Simplex Virus-1 (HSV-1). Among the 233 women, a high prevalence of STIs was found (89%), 63% of the women were positive for HPV and 24% were HIV positive. Treponema pallidum (TP), Trichomonas vaginalis (TV), Herpes Simplex Virus-2 (HSV-2), and Chlamydia trachomatis (CT) were detected in 17%, 14%, 8%, and 8% of the women, respectively. As a common phenomenon, vaginal discharge (90%) was the lower genital tract symptom reported by the majority of the women. Co-infection with any STI and HPV was detected in 56% (130/233) while 45% (59/130) of the co-infections were with high-risk HPV (hrHPV) genotypes. Among the HPV-positive participants, infection by TP was the most prevalent (27%). In total, 28% (66/233) of the participants were positive for any hrHPV genotypes. Co-infection with any STI and HIV was found in 15% (34/233) of the study participants. There was a significant association between HPV infection and TP (p = 0.039) and HSV-2 (p = 0.005). TV, TP, and CT-S1-CT-S2 positivity were significantly more prevalent in HIV-positive participants. Pathobionts Ureaplasma urealyticum/parvum and Mycoplasma hominis were detected in 84.0% (195/233) and 45% (105/233), respectively. This present study describes a high prevalence of STIs. Co-infection between HPV and STIs was found in the majority of the study subjects. The high prevalence of HPV emphasizes the need for HPV vaccination to prevent cervical cancer in this population. Management of STIs is also important in women presenting with gynecological symptoms., Competing Interests: No authors have competing interests, (Copyright: © 2024 Maueia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Human papillomavirus (HPV) infection is now a well-established cause of cervical cancer and other anogenital cancers. An association between human immunodeficiency virus (HIV) infection and higher HPV incidence and prevalence are commonly reported. This study was conducted to demonstrate HPV prevalence, genotypes and its characteristics, according to the HIV status in women from Maputo in Mozambique., Methods: A total of 233 participants with ages ranging from fourteen to forty-five were included. Cervical samples were collected, DNA extracted, and HPV genotyping was performed using the HPV Direct Flow CHIP Kit., Results: In total, 177 HIV-negative and 56 HIV-positive women were included in the analysis. The overall HPV prevalence was 63% and was significantly higher among HIV-positive women (79% versus 58% among HIV-negative women; p = 0.005). The prevalence of multiple HPV type infections was 32%. High-risk HPV types 52, 68, 35, 18 and 16 were the most frequent. A higher proportion of HIV-positive women had multiple HPV types compared with HIV-negative women., Conclusions: This study demonstrated a high prevalence of HPV in the study cohort. HIV-positive women were identified as having the highest HPV prevalence and infection with multiple HPV types across all ages. High-risk genotypes were the most commonly found.

Objectives: The aim of this study was to determine the prevalence of infection, genotypes and risk factors for human papillomavirus (HPV) among men who have sex with men (MSM) and transgender women living with and without HIV in Pakistan. Anal infection with HPV is very common worldwide among MSM, particularly among MSM living with HIV. The high prevalence of HIV among MSM and male-to-female transgendered individuals in Pakistan is a significant health concern since access to screening and health-seeking is often delayed in this stigmatised key population., Design: This cross-sectional study was conducted between March 2016 and November 2017., Participants, Setting and Data Collection: This study recruited MSM and transgender-women who self-reported to have had anal sex in the last 6 months, and were at least 18 years of age, from the sexual health and antiretroviral therapy centres. Structured questionnaires were administered, and blood samples were obtained to confirm HIV status. Anal swabs were collected for HPV-DNA detection and typing., Main Outcome Measures: The primary outcome was the prevalence of 'HPV-DNA infection'. The prevalence ratios (PR) were calculated using Cox proportional hazard model algorithms to analyse the association between exposure variables and HPV-infection., Results: Complete data were available for 298 MSM and transgender women (HIV +n=131; HIV-n=167). The overall HPV-DNA prevalence was 65.1% and was higher in participants living with HIV as compared with HIV-negative (87% vs 48%; χ 2 p≤0.001). Likewise, 28.9% of participants living with HIV were infected with two or more than two types of HPV as compared with 18.8% participants without HIV(χ 2 p≤0.001). The most frequent HPV type was HPV6/11 (46.9%), followed by HPV16 (35.1%), HPV18 (23.2%) and HPV35 (21.1%). HIV status (PR 2.81, 95% CI 2.16 to 3.82) and never condom use (PR 3.08, 95% CI 1.69 to 5.60)) were independently associated with prevalence of 'anal-HPV16 infection' when adjusting for confounding for age, other sexual and behavioural factors, for example, smoking and alcohol consumption., Conclusion: High prevalence of HPV indicates a substantial future risk of anal cancer in Pakistani MSM and transgender women, and particularly in those living with HIV. Current findings support anal Pap-smear HPV screening for this particular group and vaccination efforts for future generations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study aims to investigate acceptance of vaginal self-sampling for high-risk human papilloma virus (HPV) among long-term screening non-attenders at increased cervical cancer risk and to identify leverage points to promote screening adherence among these women. Forty-three long-term screening non-attenders performed home vaginal self-sampling for HPV, had positive HPV results, and subsequently attended gynecologic examination. Sixteen (37.2%) had high-grade cervical intraepithelial neoplasia (CIN2 or 3), and two had invasive cervical cancer. Forty-one of these women completed a questionnaire concerning Specific Knowledge about HPV, CIN, and cervical cancer, potential barriers to screening and views about self-sampling. Results were compared with 479 women treated for CIN2+ who attended gynecologic follow-up and also performed self-sampling. Significant multivariate predictors of long-term non-attender status compared with referents were low Specific Knowledge, high confidence in self-sampling, and potential barriers-refraining from activity to attend gynecologic examination, needing another's help to attend, and long travel time. Non-attenders citing fear/refraining from gynecologic examination as why they preferred self-sampling significantly more often had lowest Specific Knowledge compared with other non-attenders. All non-attenders could envision themselves doing self-sampling again while only 74% of referents endorsed this statement (p = 0.0003). We conclude that HPV self-sampling is an acceptable option for women at increased cervical cancer risk who have been long-term screening non-attenders. Educational outreach to enhance Specific Knowledge about HPV, CIN and cervical cancer is critical. Those non-attenders who explicitly avoid gynecologic examinations need special attention. Trial Registry: Clinicaltrials.gov NCT02750124.

High screening participation in the population is essential for optimal prevention of cervical cancer. Offering a high-risk human papillomavirus (HPV) self-test has previously been shown to increase participation. In this randomized health services study, we evaluated four strategies with regard to participation. Women who had not attended organized cervical screening in 10 years were eligible for inclusion. This group comprised 16,437 out of 413,487 resident women ages 33-60 (<4% of the screening target group). Among these 16,437 long-term nonattenders, 8,000 women were randomized to either (i) a HPV self-sampling kit sent directly; (ii) an invitation to order a HPV self-sampling kit using a new open source eHealth web application; (iii) an invitation to call a coordinating midwife with questions and concerns; or (iv) the standard annual renewed invitation letter with prebooked appointment time (routine practice). Overall participation, by arm, was (i) 18.7%; (ii) 10.7%; (iii) 1.9%; and (iv) 1.7%. The relative risk of participation in Arm 1 was 11.0 (95% CI 7.8-15.5), 6.3 (95% CI 4.4-8.9) in Arm 2 and 1.1 (95% CI 0.7-1.7) in Arm 3, compared to Arm 4. High-risk HPV prevalence among women who returned kits in study Arms 1 and 2 was 12.2%. In total, 63 women were directly referred to colposcopy from Arms 1 and 2; of which, 43 (68.3%) attended and 17 had a high-grade cervical lesion (CIN2+) in histology (39.5%). Targeting long-term nonattending women with sending or offering the opportunity to order self-sampling kits further increased the participation in an organized screening program., (© 2019 UICC.)

Background: The causal relation between high-risk human papillomavirus (HPV) and cervical cancer and its precursor lesions has led to the use of sensitive HPV molecular tests for screening. This study examined the impact of the baseline HPV status on the future risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among women with cytology negative for intraepithelial lesions or malignancy (NILM)., Methods: This was a nested case-control study including women with NILM baseline cytology participating in the Swedish cervical screening program in 2005-2007. Ninety-six cases of CIN2+ and 5 age-matched controls per case were identified through the National Cervical Screening Registry by follow-up through 2014. Baseline liquid-based cytology samples were tested for HPV. Conditional logistic regression analysis was used to calculate odds ratios (ORs) with confidence intervals (CIs)., Results: The risk of future high-grade cervical intraepithelial neoplasia (CIN) was strongly associated with the baseline HPV status. For women younger than 30 years, HPV-16/18 showed a significant association with future risk for CIN2+ (OR, 9.44; 95% CI, 3.37-26.4). Other HPV types were not significantly associated with future CIN2+ in these younger women. For women 30 years old or older, both HPV-16/18 and other HPV subtypes conferred a significant risk., Conclusions: The presence of HPV-16/18 among women with NILM cytology is associated with an elevated future risk of high-grade CIN. HPV types other than HPV-16/18 seem to have a greater impact on women 30 years old or older than younger women. Women with NILM cytology and HPV-16/18 need specific follow-up management within screening., (© 2018 American Cancer Society.)

Objective: Self-sampling to test for high risk human papilloma virus (HPV) is becoming an increasingly important component of cervical cancer screening. The aim of this observational study is to examine how women treated for high-grade cervical intraepithelial neoplasia (CIN) view HPV self-sampling., Methods: Invited to participate in the present study were patients who had undergone treatment of high-grade CIN (grade 2 or higher) and were followed-up at 6-months at the Karolinska University Hospital, Stockholm. The participants were instructed as to how to perform HPV self-sampling. Thereafter, the participants completed a questionnaire about HPV self-sampling and other cervical cancer screening methods, as well as about self-perceived risk of cervical cancer without regular gynecologic follow-up and about specific knowledge regarding HPV, CIN and cervical cancer., Results: Altogether 479 women enrolled in this study. The participation rate was 96.6%. Nearly 75% of the participants stated they would consider performing the HPV self-sampling prior to their next gynecologic follow-up. Confidence in HPV self-sampling was a significant independent predictor of willingness to perform HPV self-sampling. However, confidence in HPV self-sampling was significantly lower than confidence in Papanicolaou smears and in HPV testing with samples collected by health professionals. Higher specific knowledge about HPV, CIN and cervical cancer was also a significant independent predictor of willingness to perform HPV self-sampling, as was having travelled longer distance to attend gynecologic follow-up. Participants with lower income and without completed university education expressed significantly higher confidence in HPV self-sampling and lower confidence in Papanicolaou smears than the other women., Conclusions: To the best of our knowledge, this is the first study to examine the views of women treated for high-grade CIN vis-à-vis HPV self-sampling. The latter is an acceptable option for the vast majority of this cohort of women., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Human papillomavirus (HPV) is a well-known cause of cervical cancer, the second most frequent cancer in female African populations. This study aimed at determining the prevalence of HPV infections and the genotype distribution in young adults aged 18-24, in Maputo city, Mozambique, and to assess the suitability of commercially available HPV vaccines., Methods: This cross-sectional study was conducted between 2009 and 2011 at a youth clinic in Maputo Central Hospital. Cervical and urethral samples were obtained from 236 women and 176 men, respectively. Demographic and behavioural data were collected using structured questionnaires. HPV genotyping was performed for 35 different high, probably or possibly high-risk and low-risk HPV types using the CLART Human Papillomavirus 2., Results: HPV prevalence was 168/412 (40.8%; 95% CI 36.0 to 45.5) and was significantly higher in women than in men (63.6%vs10.2%). HPV52 was the most frequent type found in women, followed by HPV35, -16,-53, -58,-6 and -51. In men, HPV51 ranked the highest, followed by HPV6, -11,-52, -59 and -70. HIV infection and sexual debut before 18 years of age were associated with multiple HPV infections (OR 3.03; 95% CI 1.49 to 6.25 and OR 6.03; 95% CI 1.73 to 21.02, respectively). Women had a significantly higher HPV infection prevalence than men (p<0.001). The 9-valent HPV vaccine would cover 36.8% of the high-risk genotypes circulating in women in this study, compared with 26.3% and 15.8% coverage by the bivalent and quadrivalent vaccines, respectively., Conclusion: This study confirmed the high burden of HPV infections in young women in Maputo city, Mozambique. The HPV prevalence was associated with high-risk sexual behaviour. Sex education and sexually transmitted infection prevention interventions should be intensified in Mozambique. Only a proportion of the high-risk HPV genotypes (37%) were covered by currently available vaccines., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

The objective of this study was to determine the prevalence and some predictors for vaccine and non-vaccine types of HPV infections among bivalent HPV vaccinated and non-vaccinated young women in Uganda. This was a comparative cross sectional study 5.5 years after a bivalent HPV 16/18 vaccination (Cervarix®, GlaxoSmithKline, Belgium) pilot project in western Uganda. Cervical swabs were collected between July 2014-August 2014 and analyzed with a HPV genotyping test, CLART® HPV2 assay (Genomica, Madrid Spain) which is based on PCR followed by microarray for determination of genotype. Blood samples were also tested for HIV and syphilis infections as well as CD4 and CD8 lymphocyte levels. The age range of the participants was 15-24 years and mean age was 18.6(SD 1.4). Vaccine-type HPV-16/18 strains were significantly less prevalent among vaccinated women compared to non-vaccinated women (0.5% vs 5.6%, p 0.006, OR 95% CI 0.08(0.01-0.64). At type-specific level, significant difference was observed for HPV16 only. Other STIs (HIV/syphilis) were important risk factors for HPV infections including both vaccine types and non-vaccine types. In addition, for non-vaccine HPV types, living in an urban area, having a low BMI, low CD4 count and having had a high number of life time sexual partners were also significant risk factors. Our data concurs with the existing literature from other parts of the world regarding the effectiveness of bivalent HPV-16/18 vaccine in reducing the prevalence of HPV infections particularly vaccine HPV- 16/18 strains among vaccinated women. This study reinforces the recommendation to vaccinate young girls before sexual debut and integrate other STI particularly HIV and syphilis interventions into HPV vaccination packages.

Objective: Costs associated with HPV-related diseases such as cervical dysplasia, cervical cancer, and genital warts have not been evaluated in Sweden. These costs must be estimated in order to determine the potential savings if these diseases were eradicated and to assess the combined cost-effectiveness of HPV vaccination and cervical cancer screening. The present study aimed to estimate prevention, management, and treatment costs associated with cervical dysplasia, cervical cancer, and genital warts from a societal perspective in Sweden in 2009, 1 year before the quadrivalent HPV vaccination program was implemented., Methods and Materials: Data from the Swedish cervical cancer screening program was used to calculate the costs associated with prevention (cytological cervical cancer screening), management (colposcopy and biopsy following inadequate/abnormal cytological results), and treatment of CIN. Swedish official statistics were used to estimate treatment costs associated with cervical cancer. Published epidemiological data were used to estimate the number of incident, recurrent, and persistent cases of genital warts; a clinical expert panel assessed management and treatment procedures. Estimated visits, procedures, and use of medications were used to calculate the annual cost associated with genital warts., Results: From a societal perspective, total estimated costs associated with cervical cancer and genital warts in 2009 were €106.6 million, of which €81.4 million (76%) were direct medical costs. Costs associated with prevention, management, and treatment of CIN were €74 million; screening and management costs for women with normal and inadequate cytology alone accounted for 76% of this sum. The treatment costs associated with incident and prevalent cervical cancer and palliative care were €23 million. Estimated costs for incident, recurrent and persistent cases of genital warts were €9.8 million., Conclusion: Prevention, management, and treatment costs associated with cervical dysplasia, cervical cancer, and genital warts are substantial. Defining these costs is important for future cost-effectiveness analyses of the quadrivalent HPV vaccination program in Sweden.

Objective: Diagnoses of atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSIL) are common, but the corresponding risk of disease varies by human papillomavirus (HPV) status, complicating management strategies. Our aim was to estimate the longer-term risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) among women with ASCUS/LSIL by age, HPV status, and genotype(s)., Methods: A total of 314 women with ASCUS/ LSIL were followed for a median of 3.8 years. Baseline HPV status was determined by reflex testing and women with histologically confirmed CIN2+ were identified through linkage to the Swedish National Quality Register for Cervical Cancer Prevention. Cumulative incidence and hazard ratios were estimated to explore differences between index data and associations with CIN2+., Results: In total, 89 women (28.3%) developed CIN2+. High-risk (HR) HPV-positive women developed significantly more CIN2+ than HR-HPV-negative women (cumulative incidence 3.5 years after the index test: 42.2%, 95% CI: 32.5-53.5 for HPV16/18; 36.2%, 95% CI: 28.3-45.4 for other HR-HPV types; and 2.0%, 95% CI: 0.5-7.8 for HR-HPV-negative women; p<0.0001)., Conclusion: HPV status was of greatest importance in determining the risk of CIN2+. The risk was low among HPV-negative women during the first years of follow-up, suggesting these women could be followed less intensively. HPV16/18-positive women may need intensified follow-up as they showed the highest risk of CIN2+.

Cervical cancer is the second most common cancer among women in Argentina and the mortality rate is not declining despite opportunistic screening. Free-of-charge human papillomavirus (HPV) vaccination of 11-year-old girls was introduced in 2011. Parental acceptance of HPV vaccination is considered to be of great importance for HPV vaccine uptake. However, little is known regarding this factor in Argentina. The aim of the present study was to explore maternal HPV vaccination acceptance, willingness to pay for HPV vaccination and correlates of this willingness, awareness of HPV and HPV-associated disease and behaviors and attitudes associated with HPV vaccination acceptance. A total of 180 mothers of girls aged 9-15 years comprised this quantitative, cross-sectional, survey-based study, conducted at two hospitals in the Mendoza Province. Correlates of willingness to pay for HPV vaccination were obtained using multivariable logistic regression models. Maternal HPV vaccination acceptance was 90%, and 60% of mothers were willing to pay for HPV vaccination. Mothers who were gainfully employed and had a higher disposable household income were significantly more willing to pay for HPV vaccination [odds ratio (OR)=2.54, 95% confidence interval (CI) 1.01-6.38; OR=3.28, 95% CI 1.36-7.94, respectively], as were mothers who were aware of cervical cancer prior to the study (OR=3.22, 95% CI 1.02-10.14). Only one in 10 mothers were informed that HPV vaccination does not offer complete protection against cervical cancer. In conclusion, the present study showed high maternal HPV vaccination acceptance, although acceptance decreased when vaccination was not free-of-charge. Continuous public education campaigns are needed to improve knowledge of HPV, HPV vaccines and HPV-associated disease.

Cervical cancer is the second most common cancer among women in Argentina and the mortality has remained unchanged for the last 30 years. The 2011 national implementation of human papillomavirus (HPV) vaccination will be a key component of future cervical cancer prevention. Vaccination of young adult women is not included in the program, although these women could also benefit from the vaccine, especially in underserved areas with a high prevalence of HPV. However, research on acceptance of HPV vaccination within this group is scarce. The aim of this study was to investigate acceptance of HPV vaccination, the correlation between acceptance and cost, as well as other factors and perceptions of HPV vaccination among young adult women in Argentina. In total, 174 young women aged 18-30 years were included in this quantitative cross-sectional hospital-based study in a low resource area of the Mendoza Province, conducted through structured questionnaire-based interviews. Multinomial logistic regression models were used to investigate correlates of acceptance. Acceptance of HPV vaccination was high if it was free (95%) and even if it was not (75%). A significant positive association was found between acceptance and belief in vaccine safety (p=0.01) and between acceptance and not being a welfare recipient (p=0.00). Nearly half the participants incorrectly believed that they would be fully protected against cervical cancer after vaccination. Our findings suggest that acceptance of HPV vaccination is high among young women in a high-risk, relatively underserved area, even if vaccination is not free. Extensive misconceptions about the vaccine, however, highlight the need for further education about HPV vaccination.

Human papillomavirus (HPV) L1 capsid protein is only produced during a productive HPV infection at the end of the natural viral life cycle and is a major target of the immune response in women with HPV-related squamous intraepithelial lesions. We evaluated the usefulness of L1 detection by immunocytochemistry in high-risk (HR) HPV-positive women with minor cytological abnormalities detected at organised population-based cervical cancer screening in Sweden, and assessed the relationship with histological diagnoses. Cytological slides were immunocytochemically stained using an HPV L1-specific monoclonal antibody for all known HPV types. HPV DNA analysis was performed using Linear Array test. Out of thirteen L1-positive women infected with HPV16, only two (15.0%) progressed to cervical intraepithelial neoplasia grade 2 or worse (CIN2+); compared to four L1-positive women infected with other HR-HPV types. Among L1-positive women with CIN2+, 35.7% harboured both HR and low-risk HPV types, 25.0% harboured HR-HPV types only and 13.3% were infected with HPV16. Loss of L1 expression could be a prognostic marker for the development of preinvasive cervical lesions. We show that different HPV types may initiate a parallel oncogenic process, but only loss of L1 expression predicts the development of CIN2+, suggesting that HPV typing in combination with L1 detection could be used for more focused investigations of women with minor cytological abnormalities.

Background: Human papillomavirus (HPV) testing is not currently used in primary cervical cancer screening in Sweden, and corresponding cost-effectiveness is unclear., Objective: From a societal perspective, to evaluate the cost-effectiveness of high-risk (HR)-HPV testing using self-collected vaginal samples., Design: A cost-effectiveness analysis., Setting: The Swedish organized cervical cancer screening program., Methods: We constructed a model to simulate the natural history of cervical cancer using Swedish data on cervical cancer risk. For the base-case analysis we evaluated two screening strategies with different screening intervals: (i) cytology screening throughout the woman's lifetime (i.e. "conventional cytology strategy") and (ii) conventional cytology screening until age 35 years, followed by HR-HPV testing using self-collected vaginal samples in women aged ≥35 years (i.e. "combination strategy"). Sensitivity analyses were performed, varying model parameters over a significant range of values to identify cost-effective screening strategies., Main Outcome Measures: Average lifetime cost, discounted and undiscounted life-years gained, reduction in cervical cancer risk, incremental cost-effectiveness ratios with and without the cost of added life-years., Results: Depending on screening interval, the incremental cost-effectiveness ratios for the combination strategy ranged from €43,000 to €180,000 per life-years gained without the cost of added life-years, and from €74,000 to €206,000 with costs of added life-years included., Conclusion: The combination strategy with a 5-year screening interval is potentially cost-effective compared with no screening, and with current screening practice when using a threshold value of €80,000 per life-years gained., (© 2013 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: The objectives of this study are to investigate the human papilloma virus (HPV) distribution in vaginal cancer and to evaluate HPV-genotype as well as HPV16-variant impact on prognosis., Methods: Sixty-nine patients diagnosed with primary vaginal carcinoma (1975-2002) were included in the study. Detection of twelve high-risk HPV (hr HPV) and two low-risk HPV (lr HPV) was performed with realtime-PCR. Samples positive for HPV-16 were analyzed for variants in the E6-gene with PCR and pyrosequencing., Results: 53.6% (37/69) of the tumors were found to be HPV-positive, mostly for HPV-16 (N=26). Other HPV-types were HPV-18 (N=2), HPV-31 (N=2), HPV-33 (N=2), HPV-45 (N=1), HPV-52 (N=2), HPV-56 (N=1) and HPV-58 (N=1). Only European subtypes of HPV-16 were represented and the two most common HPV-16-variants were E-p (N=13) and E-G350 (N=11). Patients with HPV-positive tumors (N=37) had a significantly (log-rank test=3.341; p=0.0008) superior 5-year overall survival rate as well as cancer-specific survival rate and progression-free survival rate (p=0.0002; p=0.0004), compared with patients with HPV-negative tumors (N=32). Interestingly, patients with HPV-16-positive tumors had a superior overall survival compared with patients with tumors containing other HPV-genotypes. In a Cox proportional multivariate analysis age, tumor size, and HPV-status were independent and significant prognostic factors with regard to overall survival rate., Conclusions: HPV-status is of prognostic importance in vaginal carcinoma and varies with viral genotype. In this era of HPV-vaccination, genotypes other than those included in the vaccination program could still lead to vaginal carcinoma with unfavorable prognosis., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The incidence of cervical adenocarcinoma, which accounts for 10-20% of all cervical cancers, has increased continuously in developed countries during the last two decades, unlike squamous cell cervical carcinoma. This increasing trend, noted particularly among women under the age of 40 years, has occurred despite extensive cytological Pap smear screening. A deeper understanding of the etiology of cervical adenocarcinoma, better preventive measures and reliable prognostic markers are urgently needed. The human leucine-rich repeats and immunoglobulin-like domains (LRIG) gene family includes: LRIG1, LRIG2 and LRIG3. LRIG expression has proven to be of prognostic value in different types of human cancers, including breast cancer, early stage invasive squamous cervical cancer, cutaneous squamous cell carcinoma, oligodendroglioma and astrocytoma. LRIG1 functions as a tumor suppressor, while less is known about the functions of LRIG2 and LRIG3. This study evaluated the expression of the three LRIG proteins in tumor specimens from 86 women with pure cervical adenocarcinoma by immunohistochemistry. Possible correlations between LRIG expression and known prognostic factors, including human papillomavirus (HPV) status, FIGO stage and histology were investigated. Patient survival data were collected retrospectively and the possible prognostic value of LRIG protein expression was investigated. High staining intensity of LRIG1 and high fraction of LRIG3-positive cells were significantly associated with patient survival, and positive correlations were found between LRIG1 and LRIG3 staining intensity and HPV status. Thus, the LRIG proteins may be important determinants of cervical adenocarcinoma progression and their diagnostic and prognostic potential should be studied further.

Objective: To investigate the human papillomavirus (HPV) and HPV type 16-variant distribution in a series of vulvar squamous cell carcinomas (VSCC) and to evaluate the impact of HPV and HPV 16-variant on prognosis., Methods: A series of 133 patients who had a diagnosis of VSCC (1983-2008) was selected for the study. Detection of 11 high-risk HPV types (16, 18, 31, 33, 39, 45, 51, 52, 56, 58, and 59) and 2 low-risk HPV types (6 and 11) was performed with real-time polymerase chain reaction. Samples positive for HPV 16 were further analyzed for variant determination of 7 positions in the E6 gene with polymerase chain reaction and pyrosequencing., Results: Forty (30.8%) of 130 tumors were found to be HPV positive. Human papillomavirus type 16 was found in 31 cases, HPV 18 was found in 2 cases, HPV 33 was found in 5 cases, and HPV 56 and HPV 59 were found in one case each. All but one tumor harboring HPV 16 were of European linage, and the 3 most common variants were E-p (n = 13), E-G350 (n = 7), and E-G131 (n = 5). HPV positivity was associated with the basaloid tumor type and occurred in significantly younger patients. Overall and recurrence-free survival rates were better in HPV-positive cases, but after correction for age and tumor size, HPV status was no longer an independent and significant prognostic factor. The survival rates of the various HPV 16 variants were not significantly different, but there was a trend of worse outcome for the E-G131-variant group., Conclusions: Human papillomavirus positivity of 30.8% is similar to other reports on VSCC. To our knowledge, this first variant determination of HPV 16 in vulvar carcinoma in a Swedish cohort indicated that the variant E-G131 may have an increased oncogenic potential in patients with VSCC.

Human papillomavirus (HPV) causes cervical, head, and neck cancers. We studied 483 patients at a youth clinic in Stockholm, Sweden, and found oral HPV prevalence was 9.3% and significantly higher for female youth with than without cervical HPV infection (p = 0.043). Most oral HPV types matched the co-occurring cervical types.

The aim of this study was to assess the use of human papillomavirus (HPV) E6/E7 mRNA testing in the follow-up of women treated for cervical intraepithelial neoplasia (CIN) by conization and to compare the prognostic value of HPV E6/E7 mRNA to HPV L1 DNA and cytology. One hundred and forty-three women underwent cytological/histological testing, HPV DNA genotyping by Linear Array, and HPV E6/E7 mRNA testing by APTIMA HPV assay during follow-up after surgical treatment for histologically verified CIN. High-grade residual/recurrent disease (CIN2+/HSIL+) was identified in 7 (4.9%) women, and low-grade disease (CIN1/LSIL) in 25 (17.5%). At the inclusion visit 33 (23%) women were HPV DNA-positive; 13 (9.0%) were HPV E6/E7 mRNA-positive. HPV E6/E7 mRNA did not identify three women with high-grade disease. Presence of high-risk HPV DNA at the inclusion visit predicted 100% (95% CI 64.6-100) of high-grade residual/recurrent disease, with a specificity of 80.9% (95% CI 73.5-86.6); cytology had a sensitivity of 85.7%, and a specificity of 87.5%. HPV E6/E7 mRNA testing was a poor predictor of treatment failure, with a sensitivity of 57.1% (95% CI 25.0-84.2), but high specificity (93.4%; 95% CI 87.9-96.5). Detection of high-risk HPV DNA after treatment by conization identified 100% of women with residual/recurrent high-grade disease, whereas HPV E6/E7 mRNA testing was a poor predictor of treatment failure. This study suggests that a negative HPV mRNA result cannot exclude the risk of malignant progression, and that HPV E6/E7 mRNA testing by APTIMA HPV assay is not useful in the follow-up of women treated for CIN.

Knowledge of the prevalence of different human papillomavirus (HPV) types in young girls is important for the early detection of changes in HPV prevalence, e.g. due to HPV vaccines. The purpose of this study was to obtain information on the prevalence of 24 different genital HPV types in a group of sexually active young women (aged 15-23 y) attending a major youth healthcare centre in Stockholm, before the introduction of public HPV vaccination of young women in the autumn of 2010. A total of 615 women were analyzed for 24 different, mainly high-risk HPV (HR-HPV) types using multiplex polymerase chain reaction and Luminex technology. A high HPV prevalence in this cohort was demonstrated, particularly with regard to HPV16, but also to all included HR-HPV types. Of the 544 successfully analyzed samples from non-vaccinated individuals, 70% were positive for the HPV types assayed for, and 62% were positive for HR-HPV types. Over a third (34.7%) of the women were infected with HPV16, and a high frequency of infections with HR-HPV types 51 (10.7%), 18 (10.1%), 52 (9.9%) and 73 (9.4%) was also observed. At least 9 different non-vaccine HR-HPV types were present with a prevalence of >6% in this selected group of young women.

Persistent human papillomavirus (HPV) infection is a prerequisite for cervical cancer and results from bypassing the local immune response. Twenty-four volunteers underwent an ectocervical biopsy, Pap smear, tests for sexually transmitted infections including HIV and HPV genotyping. All answered a questionnaire regarding medical history. Repeat Pap smear and HPV genotyping was performed 9-26 months later. Quantitative reverse transcriptase (qRT-)PCR was used to assess expression of CD3, CD4, CD8, CD19, CD27, IL-2, IL-12, IL-4, IL-10, IL-17, HLA-DRα, TGFβ, IFNγ, PD-1, PD-L1, CTLA-4, LAG3, IgA, IgG, CCR5, CCL5/RANTES and the IL-7 receptor in the biopsies. Eleven of 24 volunteers were HPV DNA-positive at baseline. Four of 10 were infected with a persistent HPV genotype at follow-up. All target molecules were successfully amplified and quantified except for IL-4. We found no difference in mRNA expression of these molecules when comparing HPV DNA-positive and -negative women, neither when comparing persistently infected individuals or those who cleared the infection. However, mRNA expression of the B cell phenotypic marker CD19 was higher in women using hormonal contraception than those not (p<0.05). HPV infection does not evoke a local inflammatory immune response in the ectocervix measurable with qRT-PCR. Hormonal contraception may influence B cell activity in the cervix.

Human papillomaviruses (HPV) are established as a major cause of cervical carcinoma. However, causality inference is dependent on prospective evidence showing that exposure predicts risk for future disease. Such evidence is available for squamous cell carcinoma, but not for cervical adenocarcinoma. We followed a population-based cohort of 994,120 women who participated in cytological screening in Sweden for a median of 6.7 years. Baseline smears from women who developed adenocarcinoma during follow-up (118 women with in situ disease and 164 with invasive disease) and their individually matched controls (1,434 smears) were analyzed for HPV using PCR. Conditional logistic regression was used to estimate odds ratios (OR) of future adenocarcinoma with 95% confidence intervals (CI). Being positive for HPV 16 in the first cytologically normal smear was associated with increased risks for both future adenocarcinoma in situ (OR: 11.0, 95% CI: 2.6-46.8) and invasive adenocarcinoma (OR: 16.0, 95% CI: 3.8-66.7), compared to being negative for HPV 16. Similarly, an HPV 18 positive smear was associated with increased risks for adenocarcinoma in situ (OR: 26.0, 95% CI: 3.5-192) and invasive adenocarcinoma (OR: 28.0, 95% CI: 3.8-206), compared to an HPV 18 negative smear. Being positive for HPV 16/18 in 2 subsequent smears was associated with an infinite risk of both in situ and invasive adenocarcinoma. In conclusion, infections with HPV 16 and 18 are detectable up to at least 14 years before diagnosis of cervical adenocarcinoma. Our data provide prospective evidence that the association of HPV 16/18 with cervical adenocarcinoma is strong and causal.

Research on the pathogenicity of human papillomaviruses (HPVs) during cervical carcinogenesis often relies on the study of homogenized tissue or cultured cells. This approach does not detect molecular heterogeneities within the infected tissue. It is desirable to understand molecular properties in specific histological contexts. We asked whether laser capture microdissection (LCM) of archival cervical tumors in combination with real-time polymerase chain reaction and bisulfite sequencing permits (i) sensitive DNA diagnosis of small clusters of formalin-fixed cells, (ii) quantification of HPV DNA in neoplastic and normal cells, and (iii) analysis of HPV DNA methylation, a marker of tumor progression. We analyzed 26 tumors containing HPV-16 or 18. We prepared DNA from LCM dissected thin sections of 100 to 2000 cells, and analyzed aliquots corresponding to between nine and 70 cells. We detected nine to 630 HPV-16 genome copies and one to 111 HPV-18 genome copies per tumor cell, respectively. In 17 of the 26 samples, HPV DNA existed in histologically normal cells distant from the margins of the tumors, but at much lower concentrations than in the tumor, suggesting that HPVs can infect at low levels without pathogenic changes. Methylation of HPV DNA, a biomarker of integration of the virus into cellular DNA, could be measured only in few samples due to limited sensitivity, and indicated heterogeneous methylation patterns in small clusters of cancerous and normal cells. LCM is powerful to study molecular parameters of cervical HPV infections like copy number, latency and epigenetics.

Objective: To assess the use of human papillomavirus genotyping in cervical intraepithelial neoplasia posttreatment follow-up., Study Design: Prospective observational study. Ninety women underwent cytologic testing and human papillomavirus genotyping at the follow-up visit after conization. Cones were retrospectively genotyped. A second cytologic follow-up was performed., Results: Margin status and presence of cervical intraepithelial neoplasia 3+ in the cone were poor predictors of treatment outcome (sensitivity, < 50%; diagnostic odds ratio,

The aim was to evaluate human papillomavirus (HPV) 'reflex genotyping' in cases of minor cytological abnormalities detected in the gynaecological screening programme in Stockholm, Sweden. Liquid-based cytology samples showing minor cytological abnormalities were analysed using HPV genotyping (Linear Array, Roche diagnostics). Colposcopically directed cervical biopsies were obtained and the HPV test results were correlated with the histological results. In all, 63% (70/112) of the samples were high-risk (HR) HPV (HR-HPV) positive. A statistically significant correlation was found between high-grade cervical lesions and HR-HPV (P=0.019), among which HPV 16, 18, and 31 were the most important. The negative predictive value of HR-HPV detection for histologically confirmed high-grade lesions was 100%. An age limit for HPV reflex testing may be motivated in cases of low-grade squamous intraepithelial neoplasia (LSIL), because of high HR-HPV prevalence among younger women. By using HPV reflex genotyping, additional extensive workup can safely be avoided in about 50% of all cases of atypical squamous cells of undetermined significance (ASCUS) and LSIL among women 30 years. This screening strategy could potentially reduce the total abnormal cytology-reporting rate in the Swedish screening programme by about 1% and provide more accurately directed follow-up, guided by cytological appearance and HPV test results.

A total of 101 primary cervical adenocarcinomas were analyzed for the presence of p16INK4a and MIB-1 expression in correlation with the presence of 'high-risk' types of human papillomavirus (HR-HPV) and clinical outcome. We found that adenocarcinoma grading showed a significant negative correlation to p16INK4a levels (p=0.001): i.e. we found less intense p16 staining in poorly differentiated tumors than in more highly differentiated tumors as well as a highly significant correlation between HPV infection and higher levels of p16INK4a staining (p=0.00), which was similar for different HPV-types. Tumor suppressor protein p16INK4a levels were higher in HPV positive than in HPV negative tumors. Higher levels of the proliferation marker MIB-1 were associated with poorer outcome. Higher MIB-1 levels were seen in tumors with a lower grade and higher stage at diagnosis. Moreover, MIB-1 levels seem to be higher in tumors due to infection with HPV 16 and 18 compared with HPV 45. MIB-1 may be a helpful marker in grading adenocarcinoma: a high level of expression of MIB-1 indicates a low grade of tumor, whereas high expression of p16INK4a indicates a highly differentiated of the tumor. Thus, immunostaining for p16INK4a appears to be a useful diagnostic tool for cervical adenocarcinoma.

A total of 91 cervical archival biopsy series were analysed for the presence and viral load of 'high-risk' types of human papillomavirus (HR-HPV), and p16(INK4a) expression. The women had various degrees of CIN (cervical intraepithelial neoplasia). HPV 16 was the most prevalent type found, at 47% frequency. The frequency of HPV 16 increased with increasing immunoreactivity to p16(INK4a), from 39% to 44% at cases scored low to medium, to 65% at high reactivity. Thirty (33%) of the samples had negative p16(INK4a) analysis results, but were positive for HR-HPV. There was no significant correlation between viral load and the level of p16(INK4a) expression, while the grade of CIN correlated to such expressions. Thus, p16(INK4a) expression analysis yielded information which is consistent with results from the histopathology and might complement the HPV analysis in a clinical prognostic procedure in order to find women at risk for cervical cancer.

Detection of E6/E7 mRNA expression with real-time nucleic acid sequence-based amplification assay (NASBA) method (PreTect HPV-Proofer) from high-risk types of human papillomaviruses (HR-HPV) were compared with the presence of viral load, determined with quantitative real-time PCR in 80 cervical samples. Results regarding positivity and typing were in agreement using the two methods. However, there was no correlation between viral loads for HPV 16 or 18/45 and oncogene expression. Among 15 women with low grade atypia detected at a population-based cytology screening, and scored as 'within normal limits' according to histopathology, 14% were positive for oncogene expression, whereas 71% were HR-HPV positive. A correlation was observed between HR-HPV oncogene expression and high scores of p16(INK4a) positivity. Since HPV-Proofer detects full-length E6/E7 mRNA, a positive result should correlate with presence of integrated HPV, loss of HPV replication and stabilized E6/E7 full-length mRNA expression. Such expression from integrated HR-HPV generates a high and stable expression of full-length E6 proteins, which explains why a positive HPV-Proofer result was independent of viral load and correlate with high expression of p16(INK4a). Thus, E6/E7 oncogene expression analysis yielded information, which is consistent with and will complement the results from a real-time PCR method in a clinical prognostic procedure.

A series of 176 archival cervical intraepithelial neoplasia (CIN) was analysed for the presence, viral load and integration status of 'high-risk' types of human papillomavirus (HR-HPV). The samples were assayed using newly developed methods based on real-time PCR. Two methods for the extraction of DNA from the paraffin-embedded biopsies were compared: a protocol based on the MagNA pure system (Roche) and a Qiagen spin column kit (Qiagen). It was possible to amplify 94% (166) of the samples. Of these, 36, 63 and 80% of the CIN I, II and III cases contained HR-HPV. HPV 16 was the most prevalent, and was found in 20, 28 and 46% of the CIN I, II and III cases, respectively. The second most frequent HR-HPV was type 33 group, and in CIN II it was as prevalent as HPV 16. The median number of copies of HR-HPV per cell was not significantly different in the CIN I, II and III cases, but there was a wide range of viral load values over several magnitudes, regardless of the grade of CIN. All samples were found to contain integrated forms of HPV 16, frequently mixed with an episomal form.

The aim of the present investigation was to define the spectrum of oncogenic types of human papillomavirus (HPV) present in benign, pre-malignant (low-grade and high-grade squamous intraepithelial lesions, LSIL and HSIL) and malignant cervical lesions. The study comprises 215 HPV-positive biopsies, analysed with PCR, followed by sequence analyses of the HPV DNA. Fifeteen oncogenic types of HPV were identified. In 170 benign or pre-maligant alterations, the most common being HPV 16 (51%), HPV 31 (8%), HPV 18 (7%) and HPV 45 (6%). HPV 33, 35, 51, 56, 58, 66, and 70 occurred in about 1-4%. The prevalence of HPV 39, 52, 56, 59 and 73 was <1%. All the observed types of HPV, except 39 and 52, occurred in SIL lesions. The most common oncogenic HPV types (16 and 18), occurring in 45 invasive squamous carcinomas, comprised 76 per cent of the tumours, whereas less frequent HPV types (31, 33, 52, 56, 67, 70 and 73) were each found in about 2-4%. Double HPV infections were not observed. In conclusion, a total of 15 different oncogenic HPV types were identified, of which 13 types were present in pre-malignant cervical lesions and 9 in malignant lesions. This information may have some relevance when HPV analyses are considered as an adjunct to the organised screening of cervical cancer and for those working with the development of HPV vaccines for the prevention of cervical cancer.

Background: Effective screening programs have contributed to a decrease in the incidence of cervical squamous cell carcinomas but have had a limited sensitivity in the detection of adenocarcinoma precursor lesions. The aim of our study was to analyze cervical adenocarcinoma in greater detail: symptoms preceding the detection, the method of detection and the prevalence of human papillomavirus (HPV) with respect to age at diagnosis., Material and Methods: Clinical data were abstracted from the medical records of 82 women with pure invasive cervical adenocarcinomas. As diagnostic tools we used polymerase chain reaction (PCR)-based single-strand conformation polymorphism (SSCP) and/or direct DNA sequencing for HPV detection., Results: Age at diagnosis predicting factors were HPV status, positive lymph nodes, histology and stage. HPV-negativity, lymph node metastases, advanced stage and poor differentiation were all associated with a high diagnostic age. In the multivariate analysis only HPV status was shown to have an independent impact on age at diagnosis, while stage showed only borderline significance. Twenty-three percent of the cancers were detected by screening and the remaining were due to different symptoms. Among the women considered, 93% had a normal Papanicolaou (Pap) smear 3 years before diagnosis and 60% within 1 year. There was no significant correlation between smoking, oral contraceptives and HPV-positivity., Conclusions: The absence of HPV was significantly associated with a high age at diagnosis. Pap screening had a limited effect in detecting adenocarcinoma at an early stage.

In a collection of 173 cervical adenocarcinomas, the prevalence of HPV in relation to the age of women and the distribution of the various oncogenic types of HPV were evaluated. The tumour material was analysed by PCR of the HPV L1 gene followed by direct DNA sequencing and/or the polymerase chain reaction and single-strand conformation polymorphism (PCR-SSCP) technique for the identification and typing of HPV. In 68% (117/173) of the adenocarcinomas, HPV was present. A significant correlation was observed between the prevalence of HPV and age: in women younger than 40 years, HPV was present in 88%, whereas in women 60 years and older, it was found in only 39% (p<0.001). Among the HPV-positive tumours, type 18 predominated (52%) followed by type 16 (35%) and type 45 (7.7%) while other oncogenic types of HPV (31 and 59) were rarely found. HPV 16 was relatively more frequent in older women but this observation was not significant (p=0.06). HPV-typing by PCR and direct DNA sequence analysis is more specific than analysis by PCR-SSCP, especially among the less frequently occurring types of HPV. Our results further show that the prevalence of HPV in women with cervical adenocarcinomas is age-related and that the most frequently occurring types of HPV are 18, followed by 16 and 45. We have concluded that the oncogenic role of HPV in cervical squamous carcinomas and adenocarcinomas is, in some respects, discrepant.

Background: Infertile women in Sweden are offered in vitro fertilization (IVF) within the frame of the social security system. The present investigation was undertaken to evaluate the prevalence of genital human papilloma virus (HPV) infection in relation to the results of cytologic screening and to the infertility in these women., Material and Methods: Two hundred and fourteen women, mean age 32 years (range 20-40), admitted to the Center for Reproduction at Uppsala University Hospital for investigation of infertility and IVF were studied. Human papilloma virus tests were performed by a sensitive polymerase chain reaction-based technique in cervical smears obtained at a medical examination or during oocyte retrieval. Cytologic screening results were obtained from medical records or at the time of investigation. The infertile women were compared with 197 healthy female controls., Results: Infertility resulted from female factors in 47% and male factors in 29% of the cases, and remained unexplained in 24%. Seven percent of the infertile women were HPV-positive compared with 9.1% of the controls. Only genital and oncogenic HPV types were identified. Human papilloma virus type 16 was most prevalent, and examination of the HPV 16 E6 gene showed that this prototype predominated over variants. No correlation was found between HPV infection and cause of infertility. Abnormal cytology was observed in 2.3% of the infertile women and 4.1% of the controls., Conclusions: Human papilloma virus infections might appear somewhat less frequently in infertile women admitted for IVF than in a control population. In both groups HPV infection was more common than cytologic abnormalities, possibly indicating that present HPV tests are more sensitive in detecting HPV infections than cytologic screening.

Human papillomavirus (HPV) is considered the single most important co-factor in the development of cervical squamous cell carcinomas. Adenocarcinomas of the cervix are also related to HPV, but the correlation is reported to be less pronounced. In the present study, 131 cervical adenocarcinomas were identified through the Swedish Cancer Registry, examined morphologically and then analysed with sensitive polymerase chain reaction (PCR)-based HPV methods for a study of age-related prevalence of HPV. HPV was identified in 64% of the tumours after PCR amplification of the HPV L1 gene only and in 71% following PCR amplification of both the L1 and E6 genes of HPV. HPV 18 was the most prevalent (52%), followed by HPV 16 (33%) and other types of HPV (15%). The prevalence of HPV was shown to be age-dependent. In women younger than 40 years, HPV was present in 89%, whereas in women 60 years and older, HPV was observed in only 43%. The difference was statistically significant, P<0.005. The HPV-positive adenocarcinomas were represented by an age distribution similar to that of cervical squamous carcinomas with a maximum age, in the 40-49 year old group, whereas the frequency of HPV-negative adenocarcinomas increased with age, typical of most carcinomas occurring in elderly women.

A previous Swedish study revealed that both prototype and variant HPV16 E6 oncoprotein, occur in about equal numbers in high-grade cervical intraepithelial neoplasia (HCIN), whereas variant HPV16 predominates in invasive cervical squamous carcinoma. Most of the malignant HPV16 variants contain a common mutation, L83V, in the E6 oncoprotein. In the present investigation, 28 HPV16 positive, invasive cervical adenocarcinomas were collected from a total number of 131 adenocarcinomas. These HPV16-positive cases were evaluated with analysis of the E6 gene, using a recently described PCR-SSCP method for identification of the specific mutation (L83V) in the E6 gene. The results obtained were correlated to findings in 103 preinvasive, HCIN, and 31 invasive cervical squamous carcinomas also infected with HPV16. The HPV16 E6 variant L83V was present in 40% of the HCIN lesions, in 54% of the invasive adenocarcinomas, in comparison to 81% of the invasive squamous carcinomas. The difference between HCIN and squamous carcinomas was statistically significant, P < 0.001, whereas the difference between HCIN and invasive adenocarcinomas was not statistically significant, P = 0.604. Prototype HPV16 and its E6 variant L83V are both prevalent in preinvasive and invasive cervical lesions in Swedish women. However, the obvious predominance of HPV16 variant in squamous carcinomas was not seen in adenocarcinomas. A single amino-acid shift in the HPV16 E6 gene appears to result in a different transforming potential in squamous and glandular cervical lesions.

Anal warts are, from an aetiological point of view, a diverse category of lesions including condylomata acuminata, fibroepithelial polyps and seborrhoeic keratosis. Human papillomavirus induced anal warts, in contrast to other types of warts, are contagious and not infrequently sexually transmitted, they therefore need to be accurately identified. A total of 24 anal warts were randomly collected and the histopathological diagnoses based on microscopy, alone or in combination with a sensitive PCR-based human papillomavirus test, were compared using the SHARP Signal system for detection. Three lesions were identified as condyloma acuminatum by morphology alone due to the obvious presence of koiloytotic atypia; 11 warts without koilocytes were identified only after a positive test for anogenital human papillomavirus. One additional lesion contained human papillomavirus DNA of cutaneous type and 9 papillomas were human papillomavirus-negative and tentatively diagnosed as fibroepithelial polyps or seborrhoeic keratosis. All 14 condylomas contained human papillomavirus of low-risk type. Of these, 12 warts showed a positive human papillomavirus reaction with in situ hybridization. Morphology alone cannot reveal the true nature of most anal papillomas, even when koilocytotic atypia is considered as a diagnostic hallmark. An optimal diagnosis of anal warts requires a sensitive PCR-based human papillomavirus DNA test. A test for identification of cutaneous human papillomavirus DNA is also worthwhile.