Comprehensive evaluation of vaginal intraepithelial neoplasia development after hysterectomy: insights into diagnosis and treatment strategies.

Vaginal intraepithelial neoplasia (VaIN), a precancerous lesion associated with human papillomavirus (HPV), impacts women's health and quality of life. However, the natural progression of VaIN after hysterectomy remains uncertain, due to its low incidence. The existing literature predominantly consists of single-center retrospective studies lacking robust evidence-based medicine. The management of VaIN after hysterectomy is diverse and controversial, lacking a consensus on the optimal approach. Therefore, it is imperative to investigate the development of VaIN after hysterectomy, emphasizing the importance of accurate diagnosis and effective management strategies.

Distribution of HPV types among women with HPV-related diseases and exploration of lineages and variants of HPV 52 and 58 among HPV-infected patients in China: A systematic literature review.

To summarize the distribution of types of human papillomavirus (HPV) associated with HPV-related diseases and investigate the potential causes of high prevalence of HPV 52 and 58 by summarizing the prevalence of lineages, sub-lineages, and mutations among Chinese women. We searched PubMed, EMBASE, CNKI, and WanFang from January, 2012 to June, 2023 to identify all the eligible studies. We excluded patients who had received HPV vaccinations. Data were summarized in tables and cloud/rain maps. A total of 102 studies reporting HPV distribution and 15 studies reporting HPV52/HPV58 variants were extracted. Among Chinese women, the top five prevalent HPV types associated with cervical cancer (CC) were HPV16, 18, 58, 52, and 33. In patients with vaginal cancers and precancerous lesions, the most common HPV types were 16 and 52 followed by 58. For women with condyloma acuminatum (CA), the most common HPV types were 11 and 6. In Chinese women with HPV infection, lineage B was the most prominently identified for HPV52, and lineage A was the most common for HPV58. In addition to HPV types 16, which is prevalent worldwide, our findings revealed the unique high prevalence of HPV 52/58 among Chinese women with HPV-related diseases. HPV 52 variants were predominantly biased toward lineage B and sub-lineage B2, and HPV 58 variants were strongly biased toward lineage A and sub-lineage A1. Further investigations on the association between the high prevalent lineage and sub-lineage in HPV 52/58 and the risk of cancer risk are needed. Our findings underscore the importance of vaccination with the nine-valent HPV vaccine in China.

Comparing the effects of argon plasma coagulation and interferon therapy in patients with vaginal intraepithelial neoplasia: a single-center retrospective study.

PURPOSE: This study aimed to evaluate the clinical efficacy and safety of argon plasma coagulation (APC) therapy and interferon therapy in patients with grade I and II vaginal intraepithelial neoplasia (VaIN). METHODS: A total of 112 patients with VaIN were diagnosed via colposcopy-induced biopsy and classified into the APC group (n = 77) and interferon group (n = 35). Clinical data including age, grade, symptoms, historical or concomitant neoplasia of the lower genital tract, indications for hysterectomy, pregnancy history, cytology, human papillomavirus (HPV) subtype, treatment modalities, and clinical outcomes were analyzed, retrospectively. Complications and clinical outcomes were assessed at 6- and 12-month follow-ups. RESULTS: There was no significant difference in the HPV clearance rate between the APC (53.42%) and interferon (33.33%) groups at 6 months after treatment. However, the 12-month follow-up of the APC group showed a significantly higher HPV clearance rate as compared to the interferon group (87.67% vs. 51.52%, P < 0.05). The APC group exhibited a significantly higher cure rate (79.22% vs. 40.0%) and lower persistence rate (12.99% vs. 37.14%) than the interferon group (P < 0.05). Adverse reaction analysis revealed that the primary reaction in the APC group was vaginal drainage, in contrast to the increased vaginal discharge in the interferon group; though the difference was significant (68.83% vs. 28.57%, P < 0.05), no serious complications were observed. CONCLUSIONS: Treatment with APC is a safe and more effective procedure against VaIN I and II, compared to interferon. APC may serve as a viable alternative to other physiotherapies.

Antibodies against high-risk human papillomavirus proteins as markers for noncervical HPV-related cancers in a Black South African population, according to HIV status.

Human papillomavirus (HPV) proteins may elicit antibody responses in the process toward HPV-related malignancy. However, HPV seroepidemiology in noncervical HPV-related cancers remains poorly understood, particularly in populations with a high prevalence of human immunodeficiency virus (HIV). Using a glutathione S-transferase-based multiplex serology assay, antibodies against E6, E7 and L1 proteins of HPV16 and HPV18 were measured in sera of 535 cases of noncervical HPV-related cancers (anal (n = 104), vulval (n = 211), vaginal (n = 49), penile (n = 37) and oropharyngeal (n = 134)) and 6651 non-infection-related cancer controls, from the Johannesburg Cancer Study that recruited Black South African with newly diagnosed cancer between 1995 and 2016. Logistic and Poisson regression models were used to calculate adjusted odds ratios (aOR) and prevalence ratios (aPR) and 95% confidence intervals (CI) in cases versus controls. HPV16 E6 was more strongly associated with noncervical HPV-related cancers than HPV16 L1 or E7, or HPV18 proteins: anal (females (HPV16 E6 aOR = 11.50;95%CI:6.0-22.2), males (aOR = 10.12;95%CI:4.9-20.8), vulval (aOR = 11.69;95%CI:7.9-17.2), vaginal (aOR = 10.26;95%CI:5.0-21), penile (aOR = 18.95;95%CI:8.9-40), and oropharyngeal (females (aOR = 8.95;95%CI:2.9-27.5), males (aOR = 3.49;95%CI:1.8-7.0)) cancers. HPV16-E6 seropositivity ranged from 24.0% to 35.1% in anal, vulval, vaginal and penile cancer but was significantly lower (11.2%) in oropharyngeal cancer. After adjustment for HIV, prevalence of which increased from 22.2% in 1995-2005 to 54.1% in 2010-2016, HPV16 E6 seropositivity increased by period of diagnosis (aPR for 2010-2016 vs. 1995-2006 = 1.84;95%CI:1.1-3.0). Assuming HPV16 E6 seroprevalence reflects HPV attributable fraction, the proportion of certain noncervical-HPV-related cancers caused by HPV is increasing over time in South Africa. This is expected to be driven by the increasing influence of HIV.

The risk of vaginal, vulvar and anal precancer and cancer according to high-risk HPV status in cervical cytology samples.

High-risk human papillomavirus (hrHPV) is the cause of virtually all cervical cancers, most vaginal and anal cancers, and some vulvar cancer cases. With HPV testing becoming the primary screening method for cervical cancer, understanding the link between cervical hrHPV infection and the risk of other anogenital cancers is crucial. We assessed the risk of vulvar, vaginal and anal cancer and precancer (VIN2+, VaIN2+ and AIN2+) in a prospective cohort study including 455,349 women who underwent cervical hrHPV testing in Denmark from 2005 to 2020. We employed Cox proportional hazard models, adjusting for age, calendar year and HPV vaccination status, and estimated hazard ratios (HRs) and 95% confidence intervals (CI). We used the Aalen Johansen estimator to calculate the absolute risks of VIN2+, VaIN2+ and AIN2+. In total, 15% of the women were hrHPV positive at baseline. A positive cervical hrHPV test was associated with increased incidence of vulvar, vaginal and anal squamous cell carcinoma (SCC). Five-year risk estimates of VIN2+, VaIN2+ and AIN2+ among hrHPV-positive women (0.45%, 0.14% and 0.12%) were higher than among hrHPV-negative women (0.14%, 0.01% and 0.05%). Particularly high risk was observed among the hrHPV-positive women of the oldest age, with a history of anogenital precancer and those not HPV vaccinated. In conclusion, our study confirms the association between cervical hrHPV infection and non-cervical anogenital precancers and cancers. Currently, no established risk threshold or guidelines for follow-up. As HPV testing becomes the primary method for cervical cancer screening, future data will help define high-risk groups and acceptable risk thresholds.

A retrospective study of cytology and HPV genotypes results of 3229 vaginal intraepithelial neoplasia patients.

To analyze the distribution of human papillomavirus (HPV) genotype, cytology, and the clinical characteristics of vaginal intraepithelial neoplasia (VaIN). All patients with histological-proven VaIN at West China Second University Hospital, between January 1, 2014, and October 1, 2020, were retrospectively identified. The demographics, medical history, HPV genotype, viral load, and cytology results were retrieved. Standard statistical analyses were conducted. Of 3229 patients included, 42.3% were diagnosed with VaIN 1, 30.3% with VaIN 2% and 27.4% with VaIN 3. Patients with VaIN 3 were the oldest (p < 0.001). The leading HPV genotypes were HPV 16, 52, 58, 53, 56 and 81. The positive rate of HPV 16 was positively correlated with the grade of VaIN and infected most VaIN 3 patients (76.0%). The sensitivities of cytology for VaIN only, concomitant VaIN, and VaIN after hysterectomy were 75.6%, 78.8%, and 82.9%, respectively (p = 0.013), and the sensitivities of HPV were 91.1%, 93.5%, and 91.7%, respectively (p = 0.205). Cotesting improved the sensitivities, up to 96.9%, 97.1%, and 98.1%, respectively. VaIN can occur alone or be concomitant with cervical or vulvar intraepithelial neoplasia. Most of those with VaIN 2/3 are infected with HPV 16. The sensitivity of cytology and HPV testing is non-inferior to that of cervical intraepithelial neoplasia 2+. Therefore, these testings might be helpful in the early detection of VaIN.

The prognostic significance of HPV, p16, and p53 protein expression in vaginal cancer: A systematic review.

INTRODUCTION: Human papillomavirus (HPV), p16, and p53 have been investigated as prognostic markers in various HPV-related cancers. Within the field of vaginal cancer, however, the evidence remains sparse. In this systematic review, we have compiled the presently published studies on the prognostic significance of HPV and immunohistochemical expression of p16 and p53 among women with vaginal cancer. MATERIAL AND METHODS: We conducted a systematic search of PubMed, Embase, and Cochrane Library to identify relevant studies published until April 2021. We included studies reporting survival after histologically verified vaginal cancers tested for HPV, p16, and/or p53. Survival outcomes included overall survival, disease-free survival, disease-specific survival, and progression-free survival. RESULTS: We included a total of 12 studies. The vast majority of vaginal cancer cases included in each study were squamous cell carcinomas (84%-100%). Seven studies reported survival after vaginal cancer according to HPV status, and the majority of these studies found a tendency towards improved survival for women with HPV-positive vaginal cancer. Three out of four studies reporting survival according to p16 status found an improved survival among women with p16-positive vaginal cancer. For p53, only one of six studies reported an association between p53 expression and survival. CONCLUSIONS: This systematic review suggests that women with HPV- and p16-positive vaginal cancer have an improved prognosis compared with those with HPV- or p16-negative vaginal cancer. Results for p53 were varied, and no conclusion could be reached. Only 12 studies could be included in the review, of which most were based on small populations. Hence, further and larger studies on the prognostic impact of HPV, p16, and p53 in vaginal cancer are warranted.

Risk factors analysis of persistence, progression and recurrence in vaginal intraepithelial neoplasia.

OBJECTIVE: to profile patients with vaginal intraepithelial neoplasia (VAIN), to evaluate natural history and to identify risk factors for persistence, progression and recurrence. METHODS: At West China Second University Hospital, all patients with histologically confirmed VAIN over a five-year period with minimum follow-up of 6 months were retrospectively identified. Demographics, medical history and clinical information related to the diagnosis and treatment were extracted. Clinical outcomes included normalization, persistence, progression and recurrence. We evaluated risk factors by univariate and multivariate analyses. RESULTS: A total of 1478 patients fulfilled the inclusion criteria with a median follow-up of 14 months (range, 6-60 months). In 86.6% of patients, VAIN went into normalization, 6.4% persisted, 3.5% progressed and 3.5% recurred. Besides, 24 (7.1%) VAIN 3 patients and 4 (0.8%) progressed to cancer, accounting for 85.7% and 14.3% of cancer cases, respectively. VAIN 3 patients treated with excision yielded superior outcomes. Risk factors for persistence were HPV 16, 56, 59 and 43 infections, for progression were prior hysterectomy for cervical lesions and HPV 56 infection, for recurrence were HPV 61 infection. CONCLUSION: Although VAIN will regress in most patients, there are still risks of persistence, recurrence and progression, even malignancy. Therefore, a long-term follow-up is recommended. Patients with VAIN 3 are at higher risk of progressing to cancer and excision is preferred. HPV 16, 56, 59 and 43 infections might associate with an increased risk of persistence and patients with prior hysterectomy for cervical lesions tend to progress.

Human Papilloma Virus 18-Positive Submucosal Small Cell Neuroendocrine Carcinoma of the Vagina: An Immunohistochemical and Genomic Study.

Primary vaginal neuroendocrine carcinoma (NEC) is extremely rare among female genital tract tumors. Here, we report 2 cases of vaginal small cell NEC (SCNEC) using immunohistochemistry and next-generation sequencing (NGS) analysis. The 2 patients were in their mid-to-late 70s, presented with abnormal vaginal bleeding and had a vaginal submucosal mass. The biopsied or resected tumors showed a typical neuroendocrine morphology consisting of solid nests of atypical tumor cells, with no specific organoid patterns, and proliferating in the vaginal submucosa. Immunohistochemical analysis showed strong and diffuse expression of chromogranin A, synaptophysin, and p16, but no thyroid transcription factor 1 expression. Additionally, both cases were positive for human papillomavirus (HPV) 18. An NGS-based cancer panel analysis revealed that the tumors carried NF1 and AR mutations, but no major driver mutations were detected. The results of this study suggested that HPV18 infection is linked to vaginal SCNEC.

The Incidence and Prevalence of Human Papilloma Virus-associated Cancers in IBD.

AIM: The human papilloma virus has been associated with anal, cervical, vaginal, and penile cancers. The primary aim of this population-based study is to determine whether HPV-associated cancers are more commonplace in patients with inflammatory bowel disease (IBD). METHOD: The Hospital Episode Statistics (HES) database from 1997 to 2012, linked with officer for age standardized rates (ASR), were calculated using population data, and Cox regression analysis was used to determine whether IBD patients have poorer survival compared with non-IBD patients. RESULTS: A total of 61,648 patients were included in this study; of these, 837 patients had a preexisting diagnosis of IBD (1.4%). Inflammatory bowel disease patients had a significantly higher ASR of anal cancers than the non-IBD population: 5.5 per 100,000 in the IBD group compared with 1.8 in the non-IBD group. The IBD group was also diagnosed with anal cancers at a younger age (60 years compared with 66 years in the non-IBD group, P < 0.001). The survival of IBD patients with anal cancer was also poorer than the non-IBD group (hazard ratio, 1.32; 95% confidence interval, 1.15-1.52; P < 0.001). On average, survival was significantly shorter in the IBD group with anal cancer (46 months) compared with the non-IBD group (61 months, P < 0.001). Age standardized rates for cervical cancer was significantly higher in the IBD group (5.2 of 100,000) compared with the non-IBD group (4.6 of 100,000 P = 0.042). CONCLUSION: Patients with IBD have a higher rate of anal cancer compared with the general population. Survival is also worse for anal cancers in the IBD group.

Vaginal intraepithelial neoplasia in patients after total hysterectomy.

OBJECTIVES: To investigate the incidence of vaginal intraepithelial neoplasia (VaIN) after total hysterectomy and, subsequently, optimize the follow-up strategy of patients after hysterectomy. METHODS: This retrospective study was conducted on 8581 patients with benign gynecology disease who underwent total hysterectomy in our institution between January 2006 to December 2017, including 834 patients with cervical intraepithelial neoplasia (CIN) and 7747 patients without cervical lesions before hysterectomy. All patients underwent postoperative high-risk human papilloma virus (Hr-HPV) screening and liquid-based cytology test (LCT) as confirmatory tests. Colposcopies were performed if the results of the confirmatory tests were abnormal, and biopsies were performed depending on colposcopy images. The mean follow-up time was 33.8 ± 12.1 months. The relationship among VaIN, CIN, and confirmatory test results was investigated. RESULTS: VaIN was found in 81 patients after hysterectomy (incidence rate, 0.9%). The incidence rates of VaIN in patients with and without CIN history were significantly different (7.3%, 61/834, vs 0.3%, 20/7747; P < 0.05). Compared with patients without CIN history, those with CIN history were more likely to have abnormal LCT results in the postoperative follow-up, especially low-grade squamous intraepithelial lesions or worse (P < 0.001). Patients with high-grade squamous intraepithelial lesions in the LCT have a high VaIN incidence (patients with CIN history, 57.1%; patients without CIN history, 15.1%), and the 2 patients with squamous cell carcinoma or adenocarcinoma (SCC/AC) in the LCT had CIN and VaIN or worse after hysterectomy. The Hr-HPV infection rates after the hysterectomy of patients with and without CIN history were 18.8% (157/834) and 5.4% (419/7747), respectively. The incidences morbidities of VaIN in patients with persistent Hr-HPV infection and in those with and without CIN history were 35.7% and 12.0%, respectively, and were significantly higher than those in patients with negative Hr-HPV (patients with CIN history, 0.7%; patients without CIN history, 0.1%; P = 0.002). The incidence of VaIN in patients with CIN history with HPV-16 infection after hysterectomy was as high as 50%, but in patients without CIN history, the incidences of different Hr-HPV subtypes were not significantly different (P = 0.953). CONCLUSION: Patients with CIN history were more prone to VaIN and SCC after hysterectomy than were patients without CIN history. Patients should be screened thoroughly for cervical and vaginal lesions before hysterectomy. After hysterectomy, patients with CIN history should undergo lifetime annual LCT and HPV screening.

Incidence of human papillomavirus-related anogenital precancer and cancer in women with diabetes: A nationwide registry-based cohort study.

In this register-based cohort study, we estimated the incidence of human papillomavirus (HPV)-related anogenital precancer and cancer in women with diabetes compared with women without diabetes. We followed all women living in Denmark born 1916 to 2001 (n = 2 508 321) for individual-level information on diabetes (Type 1 or 2 [T1D or T2D]), diagnoses of cervical, vaginal, vulvar and anal intraepithelial neoplasia Grade 2 or 3 (IN2/3) and cancer and other covariates from nationwide registries. We used Poisson regression to model the incidence rates of anogenital IN2/3 and cancer as a function of diabetes status, age, HPV vaccination, education, calendar year, and cervical cancer screening status. Incidence rate ratios (IRRs) were estimated for diabetes overall, and separately for T1D and T2D, compared with women without diabetes. Women with diabetes had higher rates of vulvar IN2/3 (IRR = 1.63; 95% confidence interval [CI]: 1.41-1.88), vulvar cancer (IRR = 1.61; 95% CI: 1.36-1.91) and vaginal cancer (IRR = 1.79; 95% CI: 1.27-1.91) than women without diabetes. Similar patterns were observed for anal IN2/3, anal cancer and cervical cancer, although not statistically significant. In contrast, women with diabetes had lower rates of cervical IN2/3 (IRR = 0.74; 95% CI: 0.69-0.79) than women without diabetes. Patterns were generally similar in women with T1D and T2D, although cancer rates were higher in women with T2D. In conclusion, the incidence of most anogenital precancers and cancers were increased in women with diabetes. However, women with diabetes had lower incidence of cervical precancer. Our findings could be explained by biological mechanisms and/or behavioral factors, such as smoking and less frequent cervical screening participation.

Incidence, cost and gender differences of oropharyngeal and noncervical anogenital cancers in South Korea.

BACKGROUND: Human papillomavirus (HPV) is associated with a significant public health burden, yet few studies have been conducted in Asia, especially on noncervical cancers. We estimated the incidence and cost of oropharyngeal and noncervical anogenital (anal, vulvar, vaginal, penile) cancer in Korea. METHODS: We conducted a retrospective cohort study using Korea's National Health Insurance (NHI) claim database from 2013 to 2016. The main outcome measures were the number of respective cancer incidences during the study period and the annual costs per patient in the first year after diagnosis, which was adjusted by relevant variables based on the regression analysis. RESULTS: During the study period, 8022 patients with these cancers were identified, and oropharyngeal cancer comprised 46% of them. The crude incidence rate for male oropharyngeal cancer was significantly higher than that of females (3.1 vs. 0.7 per 100,000 as of 2016, respectively). Additionally, the crude incidence of male oropharyngeal cancer increased from 2.7 in 2013 to 3.1 in 2016, whereas that of female and other cancers was stable during the study period. The mean annual incidence-based cost per patient in 2016 was highest for oropharyngeal cancers (21,870 USD), and it was significantly higher in males than in females based on then regression analysis (p < .001). CONCLUSIONS: Oropharyngeal cancer comprises the highest number of HPV-associated noncervical cancer incidences in Korea, and the incidence and cost of oropharyngeal cancer was significantly higher among males than females. More aggressive public health policy toward males may decrease gender gap of oropharyngeal cancer.

Good performance of p16/Ki-67 dual-stain cytology for detection and post-treatment surveillance of high-grade CIN/VAIN in a prospective, cross-sectional study.

BACKGROUND: The limited sensitivity of Papanicolaou (Pap) cytology and the low specificity of HPV testing in detecting cervical or vaginal lesions means that either precancers are missed or women without lesions are overtreated. To improve performance outcomes, p16/Ki-67 dual-stain cytology has been introduced as a useful biomarker. METHODS: A prospective, cross-sectional study was performed and included 599 patients. Clinical performance estimates of Pap cytology, HPV DNA assay, and p16/Ki-67 dual-stain cytology for the detection of CIN2+/VAIN2+ were determined and compared. RESULTS: The sensitivity and specificity of p16/Ki-67 dual-stain cytology in detecting histology proven CIN2+/VAIN2+ was 91.6% and 95.0%, respectively, while that of Pap cytology was 42.1% and 95.2%, respectively, and that of HPV DNA testing was 100% and 41.6%, respectively. Among the three tests, the AUC of p16/Ki-67 immunocytochemistry was the largest, both for detecting cervical lesions and vaginal lesions, at 0.932 and 0.966, respectively. Among women who were HPV 16/18 positive or 12-other hrHPV positive and Pap positive (≥ASCUS), dual staining reduced the number of unnecessary colposcopy referrals from 274 to 181. Among the women who were 12-other hrHPV positive and Pap negative, dual staining could prevent underdiagnosis in six patients with CIN2+/VAIN2+ when used as a triage marker. Dual staining also identified four women with high-grade lesions detected by diagnostic conization but with negative colposcopy-guided biopsy results. CONCLUSION: p16/Ki-67 dual staining may be a promising tool for predicting high-grade cervical and vaginal lesions.

The costs of treating vaginal and vulval cancer in England (2009-2015).

BACKGROUND: Human papillomavirus (HPV) infection is a pre-requisite for cervical cancer, which represents the third most common cancer among women worldwide. A causal relationship also exists between HPV and cancer in other areas of the female reproductive system including the vagina and vulva. Whilst the incidence of vaginal cancer in the UK has remained relatively stable over the past 25 years, vulval cancer rates are increasing. A body of literature exists on the epidemiology and aetiology of vaginal and vulval cancer, but little is known about the economic burden. The objective of this study was to quantify the costs of treating these cancers on the National Health Service (NHS) in England. METHODS: Inpatient and outpatient episodes were derived from Hospital Episode Statistics (HES). Health Resource Group (HRG) tariffs and National Reference Costs were used to estimate the cost of treating pre-cancerous and invasive vaginal and vulval lesions in England. RESULTS: The study showed that for the 5 years from 2009/2010 to 2014/2015 the total cost associated with pre-cancerous and invasive vaginal and vulval lesions was over £14 million per year on average (95% of which was attributed to inpatient costs). Vulval cancer accounted for the largest proportion; an estimated 60% of the total cost (£8.82 million). On average 4316 patients per year in England were admitted to hospital and 912 patients attended outpatient settings for pre-cancerous and invasive disease of the vagina and vulva. CONCLUSION: The results indicate that vaginal and vulval cancer cost the English health care system over £14 million per year. Given the causal role of HPV in a proportion of these cancers, preventative measures such as the national HPV immunisation programme have the potential to reduce the economic burden. To ensure optimal use of NHS resources, it is important that future economic evaluations of such preventative measures consider the full burden of HPV related disease.

HIV-positive women with anal high-grade squamous intraepithelial lesions: a study of 153 cases with long-term anogenital surveillance.

Women living with HIV (WLHIV) are at increased risk for human papillomavirus (HPV)-associated anal cancer. Given the "field effect" of HPV pathogenesis, some recommend that anal cancer screening should be limited to WLHIV with prior genital disease. This study aimed to characterize the relationship between anal and genital disease in WLHIV in order to better inform anal cancer screening guidelines. We retrospectively studied 153 WLHIV with biopsy-proven anal high-grade squamous intraepithelial lesions (AHSIL) and long-term evaluable cervical/vaginal/vulvar histopathology. Based on the absence or presence of genital HSIL, subjects were categorized as having isolated AHSIL or multicentric HSIL. Demographics, HIV parameters and cervical/anal HPV status were recorded. Chi-square test was used for bivariate analyses. Of 153 WLHIV with AHSIL, 110 (72%) had isolated AHSIL, while 43 (28%) had multicentric HSIL (28 cervical, 16 vulvar, and 8 vaginal HSIL). The median genital surveillance was 8 years (range 1-27). Cervical HPV16/18 infection was associated with multicentric disease (P = 0.001). Overall, 53% of multicentric cases presented genital HSIL preceding AHSIL with median interval 13 years (range 2-23). Paired anal and cervical high-risk HPV results were available for 60 women within 12 months of AHSIL diagnosis: 30 (50%) had anal infection alone, while 30 (50%) had anal/cervical coinfection by 16/18 (15%), non-16/18 (13%), or different types (22%). In conclusion, WLHIV frequently develop AHSILs without pre-existing genital disease or after long latency following a genital HSIL diagnosis. Our findings support anal cancer screening for WLHIV irrespective of prior genital disease.

Prevention of Human Papillomavirus Infection. Beyond Cervical Cancer: A Brief Review.

INTRODUCTION: Human papillomavirus is responsible for almost all cases of cervical cancer, an important portion of anogenital and oropharyngeal invasive and preinvasive lesions, as well as genital warts (condyloma acuminatum) and recurrent respiratory papillomatosis. Currently, three prophylactic vaccines against high-risk Human papillomavirus are commercialized in many countries worldwide. METHODS: To this non-systematic review the authors searched in MEDLINE/PubMed for systematic reviews, meta-analysis and randomized controlled trials, published in the last six years, using the terms "HPV", "non-cervical cancer" and "vaccine". Non-cervical cancers caused by human papillomavirus are less common lesions. However, its incidence has been increasing, while cervical cancer has declined, due mainly to highly effective screening programs. There are no formal screening programs for non-cervical cancers, so universal vaccination could have an important impact. The preventive effect of the vaccine is mainly studied and established in relation to cervical cancer, although it has also been demonstrated in the development of vulvar and vaginal lesions. To date, the efficacy in preventing anal and oropharyngeal diseases related with human papillomavirus is uncertain due to scarce supporting data and low vaccination coverage in men. The prevalence of injuries and subsequent absolute benefit of vaccination is lower in men, but it provides an additional benefit to the herd immunity achieved with the vaccination of women. CONCLUSION: The total fraction of malignant and pre-malignant lesions attributed to Human papillomavirus genotypes contained in the nonavalent vaccine is significant in both women and men, which turns this vaccine into a great asset in terms of Public Health.

Introdução: O vírus do papiloma humano é responsável por quase todos os casos de cancro do colo do útero, de uma importante fração de lesões anogenitais e orofaríngeas pré-invasivas e invasivas bem como de condilomas genitais e da papilomatose respiratória recorrente. Atualmente existem três vacinas profiláticas contra o vírus do papiloma humano de alto risco comercializadas em vários países do mundo. Métodos: Para esta revisão não-sistemática, os autores pesquisaram na MEDLINE/PubMed revisões sistemáticas, metanálises e ensaios clínicos randomizados, publicados nos últimos seis anos, utilizando os termos "HPV", "cancro não cervical" e "vacina". Os cancros não cervicais causados pelo vírus do papiloma humano são lesões menos comuns. Contudo, a sua incidência tem aumentado, a par de uma diminuição do cancro do colo do útero, devido principalmente à implementação de programas de rastreio altamente eficazes. Uma vez que não existem programas oficiais de rastreio para cancros não cervicais, a vacinação universal pode ter um impacto importante. O efeito preventivo da vacina é principalmente estudado e estabelecido em relação ao cancro do colo do útero, embora também tenha sido demonstrado no desenvolvimento de lesões vulvares e vaginais. Até ao momento, a eficácia na prevenção de doenças anais e orofaríngeas relacionadas com o vírus do papiloma humano é incerta, devido à escassez de dados na literatura e baixa cobertura de vacinação em homens. A prevalência de lesões e o consequente benefício absoluto da vacinação é inferior nos homens, porém proporciona um benefício adicional à imunidade de grupo alcançada com a vacinação de mulheres. Conclusão: A fração total de lesões malignas e pré-malignas atribuídas aos genótipos de vírus do papiloma humano contidos na vacina nonavalente é significativa tanto em mulheres quanto em homens, o que confere a essa vacina um grande potencial em termos de Saúde Pública.

Risk of vulvar, vaginal and anal high-grade intraepithelial neoplasia and cancer according to cervical human papillomavirus (HPV) status: A population-based prospective cohort study.

OBJECTIVES: All cervical cancers and some vulvar, vaginal and anal cancers are caused by high-risk human papillomavirus (hrHPV). However, little is known about the association between cervical HPV infection and subsequent intraepithelial neoplasia and cancer at other anogenital sites. In this prospective cohort study, we estimated the risk of vulvar, vaginal and anal intraepithelial neoplasia grade 2/3 or cancer (VIN2+, VaIN2+, AIN2+) according to cervical hrHPV status. METHODS: Liquid-based cervical cytology samples were collected from 40,399 women screened against cervical cancer in Copenhagen, Denmark, during 2002-2005. Samples were tested for hrHPV using Hybrid Capture 2 (HC2) and genotyped using INNO-LiPA. We linked the cohort with Danish nationwide registries to identify cases of VIN2+, VaIN2+ and AIN2+ during up to 15 years of follow-up. We estimated age-adjusted hazard ratios (HRs) using Cox regression and cumulative incidences using Aalen-Johansen's estimator. RESULTS: Women with cervical HPV16 infection had increased hazard of VIN2+ (HR = 2.6; 95% confidence interval [CI], 1.2-5.5), VaIN2+ (HR = 23.5; 95% CI, 6.8-81.6) and AIN2+ (HR = 3.7; 95% CI, 1.1-12.2) compared with HC2 negative women. Women with other hrHPV types than HPV16 also had increased hazard of VaIN2+ (HR = 7.1; 95% CI, 2.3-22.3) and a borderline statistically significantly increased risk of AIN2+ (HR = 2.2; 95% CI, 0.9-4.9) compared with HC2 negative women. The 10-year cumulative incidences of VIN2+, VaIN2+ and AIN2+ in women with cervical HPV16 were 0.3% (95% CI, 0.2%-0.7%), 0.2% (95% CI, 0.1%-0.5%) and 0.1% (95 CI, 0.0%-0.4%). CONCLUSIONS: Cervical HPV16 infection is associated with increased risk of VIN2+, VaIN2+ and AIN2+.

Human papillomavirus genotypes in cervical and other HPV-related anogenital cancer in Rwanda, according to HIV status.

The study aim was to describe human papillomavirus (HPV)-attributable cancer burden in Rwanda, according to anogenital cancer site, HPV type, age and HIV status. Tissue specimens of cervical, vulvar, vaginal, penile and anal cancer diagnosed in 2012-2018 were retrieved from three cancer referral hospitals and tested for high-risk (HR) HPV DNA. Cervical cancer represented the majority of cases (598 of 738), of which 96.0% were HR-HPV positive. HPV-attributable fractions in other cancer sites varied from 53.1% in 81 penile, through 76.7% in 30 vulvar, 83.3% in 24 vaginal, up to 100% in 5 anal cases. HPV16 was the predominant HR-HPV type in cervical cancer (55.0%), followed by HPV18 (16.6%) and HPV45 (13.4%). HPV16 also predominated in other cancer sites (60-80% of HR-HPV-attributable fraction). For cervical cancer, type-specific prevalence varied significantly by histology (higher alpha-9 type prevalence in 509 squamous cell carcinoma vs. higher alpha-7 type prevalence in 80 adenocarcinoma), but not between 501 HIV-negative and 97 HIV-positive cases. With respect to types targeted, and/or cross-protected, by HPV vaccines, HPV16/18 accounted for 73%, HPV31/33/45/52/58 for an additional 22% and other HR-HPV types for 5%, of HPV-attributable cancer burden, with no significant difference by HIV status nor age. These data highlight the preventive potential of the ongoing national HPV vaccination program in Rwanda, and in sub-Saharan Africa as a whole. Importantly for this region, the impact of HIV on the distribution of causal HPV types was relatively minor, confirming type-specific relevance of HPV vaccines, irrespective of HIV status.