The pathophysiology of the development of anal cancer is thought to be linked to chronic inflammation, a possible consequence of infections with human papillomavirus (HPV) or HIV, or inflammation from inflammatory bowel disease. Anal HPV-induced carcinogenesis bears similarities to its cervical counterpart via viral integration into the host genome and the development of precursor lesions termed anal intraepithelial neoplasia. HPV-16 and -18 are the most common HPV genotypes associated with anal cancer. Other risk factors for the development of anal cancer include chronic immunosuppression, sexual activity and sexually transmitted diseases, female gender, history of anogenital dysplasia, and smoking.

Anal carcinoma is a relatively rare tumor that accounts for approximately 2% of gastrointestinal malignancies and less than 7% of anorectal cancers. Most anal tumors originate between the anorectal junction and the anal verge. Risk factors for the disease include human papillomavirus infection, human immunodeficiency virus, tobacco use, immunosuppression, female sex, and older age. The pathogenesis of anal carcinoma is believed to be linked to human papillomavirus-related inflammation, leading to dysplasia and progression to cancer. Squamous cell carcinoma is the most common type of anal tumor, with an annual incidence of approximately 1 to 2 per 100000 persons. Treatment regarding anal cancer has emerged over time. However, chemoradiation therapy remains the mainstay approach for early localized disease. Patients with metastatic disease are treated with systemic therapy, and salvage surgery is reserved for disease recurrence following chemoradiation. This article aims to provide background information on the epidemiology, risk factors, pathology, diagnosis, and current trends in the management of anal cancer. Future directions are briefly discussed.

Anal cancer is a rare disease, affecting more frequently women than men, mainly related to human papillomavirus infection (HPV). Rising incidence and mortality have been reported over the past four decades in different countries.

To provide an up-to-date overview of recent trends in mortality from anal cancer, we analysed death certification data provided by the WHO in selected countries worldwide over the period from 1994 to 2020. We also analysed incidence derived from Cancer Incidence in Five Continents from 1990 to 2012 for all histologies as well as for anal squamous cell carcinoma (SCC).

The highest age-standardised mortality rates around 2020 were registered in Central and Eastern Europe, such as Slovakia (0.9/100 000 men and 0.40/100 000 women), in the UK (0.24/100 000 men and 0.35/100 000 women), and Denmark (0.33/100 000 for both sexes), while the lowest ones were in the Philippines, Mexico, and Japan, with rates below 0.10/100 000 in both sexes. Upwards trends in mortality were reported in most countries for both sexes. Similarly, incidence patterns were upward or stable in most countries considered for both sexes. In 2008-2012, Germany showed the highest incidence rates (1.65/100 000 men and 2.16/100 000 women).

Attention towards vaccination against HPV, increased awareness of risk factors, mainly related to sexual behaviours and advancements in early diagnosis and management are required to control anal cancer incidence and mortality.

People living with HIV have an increased risk of anal cancer.

To estimate anal cancer incidence and related risk factors in a national cohort of HIV-infected patients.

Prospective multicenter cohort study.

Multicenter study including patients from the Spanish HIV Research Network.

We collected data from 16,274 HIV-infected treatment-naive adults recruited from January 2004 to November 2020.

The primary outcome measures of this study were the incidence and prevalence of anal carcinoma. The secondary outcome measures included the associations between baseline and time-dependent covariables and the primary end point.

Twenty-six cases of anal cancer were diagnosed, 22 of which were incident cases resulting in a cumulative incidence of 22.29 of 100,000 person-years, which was stable during the study period. At the end of the study, 20 of the 43 centers had screening programs for high-grade anal dysplasia. Patients with anal cancer were males (26/26; 100% vs 13,833/16,248; 85.1%), were mostly men who have sex with men (23/26; 88.5% vs 10,017/16,248; 61.6%), had a median age of 43 years (interquartile range, 35-51), were more frequently previously diagnosed with an AIDS-defining illness (9/26; 34.6% vs 2429/16,248; 15%), and had lower nadir CD4 cell counts (115 vs 303 µL). About a third (34.6%, 9/26) were younger than 35 years. In multivariable analysis, men who have sex with men and patients with previous AIDS-defining illness had an 8.3-fold (95% CI, 1.9-36.3) and 2.7-fold (95% CI, 1.1-6.6) increased HR for developing anal cancer, respectively. Patients with higher CD4 cell counts during the follow-up showed a 28% lower risk per each additional 100 CD4 cell/µL (95% CI, 41%-22%).

Lack of information on some potential risk factors, screening, and treatment of high-grade anal dysplasia were not uniformly initiated across centers during the study period.

Although the overall incidence in our study was low, there was a significant number of patients younger than 35 years with anal cancer. In addition to age, other factors, such as men who have sex with men and patients with severe immunosuppression (current or past), should be prioritized for anal cancer screening.

ANTECEDENTES:Las personas portadoras del virus de la inmunodeficiencia humana tienen un mayor riesgo de cáncer anal.OBJETIVO:Nosotros queremos estimar la incidencia de cáncer anal y los factores de riesgo relacionados en una cohorte nacional española de pacientes infectados por VIH.DISEÑO:Estudio de cohortes de tipo multicéntrico y prospectivo.ÁMBITO:Se incluyeron pacientes de la Red Española de Investigación en VIH.PACIENTES:Recolectamos los datos de 16,274 adultos infectados por el VIH que nunca habían recibido tratamiento, reclutados desde enero de 2004 hasta noviembre de 2020.MEDIDAS DE RESULTADO PRINCIPALES:Las medidas de resultado primarias de este estudio fueron la incidencia y la prevalencia del carcinoma anal. Las medidas de resultado secundarias incluyeron las asociaciones entre las covariables basales y dependientes del tiempo y el criterio principal de valoración.RESULTADOS:Se diagnosticaron 26 casos de cáncer anal, de los cuales 22 fueron casos incidentales resultando con una incidencia acumulada de 22,29/100.000 personas-año que se mantuvo estable durante el período de estudio.Al final de nuestro estudio, 20 de los 43 centros referentes tenían programas de detección de displasia anal de alto grado. Los pacientes con cáncer anal eran hombres (26/26; 100% vs 13 833/16 248; 85,1%), en su mayoría hombres que mantenían sexo con otros hombres (23/26; 88,5% vs 10 017/16 248; 61,6%), la mediana de edad fue de 43 años (IQR: 3 -51), 34,6% (9/26) < 35 años, previa y frecuentemente diagnosticados con una enfermedad definitoria de SIDA (9/26; 34,6% vs 2429/16248; 15%) y que tenían un punto opuesto mucho más bajo en el recuentos de células CD4 (115 µL frente a 303 µL).En el análisis multivariable, los hombres que tenían relaciones sexuales con otros hombres y los pacientes con enfermedades definitorias de sida anteriores, tenían un aumento de 8,3 veces (IC del 95%: 1,9 a 36,3) y de 2,7 veces (IC del 95%: 1,1 a 6,6) en el cociente de riesgos instantáneos para desarrollar cáncer anal, respectivamente. Los pacientes con recuentos de células CD4 más altos durante el seguimiento mostraron un riesgo 28 % menor por cada 100 células CD4/µl adicionales (95% IC: 41%- 22%).LIMITACIONES:La falta de información sobre algunos factores potenciales de riesgo, la detección y el tratamiento de la displasia anal de alto grado no se iniciaron uniformemente en todos los centros durante el período de estudio.CONCLUSIONES:Si bien la incidencia general en nuestro estudio fue baja, hubo un número significativo de pacientes de <35 años con cáncer anal. Además de la edad, otros factores como los hombres que tienen sexo con hombres y los pacientes con inmunosupresión severa (actual o pasada) deben priorizarse para la detección del cáncer anal. ( Traducción-Dr. Xavier Delgadillo ).

Anal squamous cell carcinoma (ASCC) is an uncommon cancer that is rapidly increasing in incidence. HIV is a risk factor in the development of ASCC, and it is thought that the rapidly increasing incidence in men is related to increasing numbers of people living with HIV (PLWH). We undertook a population-based study comparing the demographics and incidence of ASCC in patients residing high HIV prevalence areas in England to patients living in average HIV prevalence areas in England.

This is a cross-sectional study following the 'Strengthening the Reporting of Observational Studies in Epidemiology' statement. Demographic data and incidence rates of ASCC within Clinical Commissioning Groups (CCGs) between 2013 and 2018 were extracted from the Cancer Outcomes and Services Dataset. CCGs were then stratified by HIV prevalence from data given by Public Health England, and high HIV prevalence geographical areas were compared with average HIV geographical areas.

Patients in high HIV areas were more likely to be young and male with higher levels of social deprivation. Incidence rates in men between 2013 and 2017 were higher in high HIV areas than average HIV areas with a rapidly increasing incidence rates in early-stage disease and a 79.1% reduction in incidence of metastatic stage 4 disease.Whereas women in high HIV areas had lower ASCC incidence than the national average and a low incidence of early-stage disease; however, metastatic disease in women had quintupled in incidence in high HIV areas since 2013.

Patients presenting with ASCC in high HIV geographical areas have different demographics to patients presenting in average HIV geographical areas. This may be related to screening programmes for PLWH in high HIV areas.

People living with human immunodeficiency virus (HIV; PLWH) have a markedly elevated anal cancer risk, largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk.

We studied 102 777 PLWH during 1996-2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures during prespecified moving time windows. We compared models using the Akaike information criterion.

Cumulative and nadir/peak CD4 or HIV RNA measures from approximately 8.5 to 4.5 years in the past were generally better predictors for anal cancer risk than their corresponding more recent measures. However, the best model included CD4 nadir (ie, the lowest CD4) from approximately 8.5 years to 6 months in the past (hazard ratio [HR] for <50 vs ≥500 cells/µL, 13.4; 95% confidence interval [CI], 3.5-51.0) and proportion of time CD4 <200 cells/µL from approximately 8.5 to 4.5 years in the past (a cumulative measure; HR for 100% vs 0%, 3.1; 95% CI, 1.5-6.6).

Our results are consistent with anal cancer promotion by severe, prolonged HIV-induced immunosuppression. Nadir and cumulative CD4 may represent useful markers for identifying PLWH at higher anal cancer risk.

Certain population groups are known to have higher than average anal cancer risk, namely persons living with HIV (PLHIV), men who have sex with men (MSM), women diagnosed with human papillomavirus (HPV)-related gynecological precancerous lesions or cancer, solid organ transplant recipients (SOTRs) and patients with autoimmune diseases. Our aim was to provide robust and comparable estimates of anal cancer burden across these groups. Summary incidence rates (IRs), as cases per 100 000 person-years (py), were calculated by fixed-effects meta-analysis. IRs were 85 (95% confidence interval [CI] = 82-89) for HIV-positive MSM (n = 7 studies; 2 229 234 py), 32 (95% CI = 30-35) for non-MSM male PLHIV (n = 5; 1626 448 py) and 22 (95% CI = 19-24) for female PLHIV (n = 6; 1 472 123 py), with strong variation by age (eg, from 16.8 < 30 years to 107.5 ≥ 60 years for HIV-positive MSM). IR was 19 (95% CI = 10-36) in HIV-negative MSM (n = 2; 48 135 py). Anal cancer IRs were much higher after diagnosis of vulvar (IR = 48 [95% CI = 38-61]; n = 4; 145 147 py) than cervical (9 [95% CI = 8-12]; n = 4; 779 098 py) or vaginal (IR = 10 [95% CI = 3-30]; n = 4; 32 671) cancer, with equivalent disparity after respective precancerous lesions. IR was 13 (95% CI = 12-15) in SOTRs (n = 5; 1 946 206 py), reaching 24.5 and 49.6 for males and females >10 years after transplant. Anal cancer IRs were 10 (95% CI = 5-19), 6 (95% CI = 3-11) and 3 (95% CI = 2-4) for systemic lupus erythematosus, ulcerative colitis and Crohn's disease, respectively. In conclusion, a unifying anal cancer risk scale, based upon comprehensive meta-analysis, can improve prioritization and standardization in anal cancer prevention/research initiatives, which are in their public health infancy.

HIV infected people are at higher risk of developing cancer, although it is globally diminished in the era of highly active antiretroviral treatment (HAART). Recently, antioncogenic properties of some HAART drugs were discovered. We discuss the role of HAART in the prevention and improvement of treatment outcomes of cancers in HIV-infected people. We describe different trends in HAART-cancer relationships: cancer-predisposing as well as cancer-preventing. We cover the roles of particular drug regimens in cancer prevention. We also describe the causes of cancer treatment with HAART drugs in HIV-negative people, including ongoing clinical studies that may directly point to a possible independent anti-oncogenic activity of HAART drugs. We conclude that despite potent antioncogenic activities of every class of HAART drugs reported in preclinical models, the evidence to date indicates that their independent clinical impact in HIV-infected people is limited. Improved cancer prevention strategies besides HAART are needed to reduce HIV-cancer-related mortality.

The effect of antiretroviral therapy (ART) on the natural history of anal high-risk HPV and anal lesion progression is not well established. We reviewed the association of ART and other HIV-related factors on anal HPV infection, anal intraepithelial neoplasia (AIN), and anal cancer among people living with HIV.

For this systematic review and meta-analysis, we searched MEDLINE and EMBASE for studies published between Jan 1, 1996, and Oct 30, 2019, that reported the association of HIV-related exposures (ART or highly active ART [HAART], HIV-RNA plasma viral load [PVL], and nadir or current CD4 cell count) with outcomes of anal high-risk HPV prevalence, incidence, and persistence; prevalence, incidence, progression, or regression of anal histological and cytological abnormalities; and anal cancer incidence. Effect estimates were extracted whenever available; otherwise, they were calculated from raw data. We assessed the risk of bias of included studies using the Newcastle-Ottawa scale, and random-effects meta-analyses were done to examine heterogeneity using the I² statistic. This study is registered on the PROSPERO database, CRD42018007271.

We identified 6777 studies, of which 5377 were excluded before full-text review. 122 studies providing estimates for 130 distinct populations matched the inclusion criteria. The populations comprised 417 006 people living with HIV (women, men who have sex with men, and men who have sex with women). 41 (32%) population estimates were not stratified by sex or sexual orientation. People living with HIV receiving ART had 35% lower high-risk HPV prevalence than ART-naive people (crude odds ratio [OR] 0·65, 95% CI 0·54-0·79; I² 12·1%, p=0·31) in 18 studies, and prolonged ART use was associated with a 10% reduction per year in high-risk HPV prevalence in two studies (adjusted OR 0·90, 0·85-0·95; I² 0%, p=0·88). People living with HIV with undetectable PVL had lower HSIL-AIN2+ prevalence than those with detectable PVL (crude OR 0·84, 0·72-0·98; I² 0%, p=0·80) in 16 studies, particularly if sustained for more than 1 year (crude OR 0·62, 0·47-0·81; I² 0%, p=0·51). ART was not associated with anal cancer incidence when adjusted for years living with HIV in three studies (adjusted hazard ratio [HR] 1·11, 95% CI 0·68-1·80; I² 0%, p=0·57), but ART users with sustained undetectable HIV PVL had 44% lower risk of anal cancer than those without (adjusted HR 0·56, 0·44-0·70; I² 0%, p=0·94) and for each increase in nadir CD4 cell counts of 100 cells per μL, there was a 40% decrease in anal cancer incidence (crude HR 0·60, 0·46-0·78; I² 21·7%, p=0·26).

Effective ART use and early initiation at high nadir CD4 counts might reduce anal high-risk HPV infection and anal cancer risk. Although most studies were cross-sectional in design and few adjusted for potential confounders, this analysis provides comprehensive estimates of the effect of ART and HIV-related factors on the natural history of anal HPV-related disease in people living with HIV.

EU Marie Skłodowska-Curie Actions programme.

Men who have sex with men who are living with HIV are at highest risk for anal cancer. Our objective was to use empirical data to develop a comprehensive disease simulation model that reflects the most current understanding of anal carcinogenesis, which is uniquely positioned to evaluate future anal cancer screening strategies and provide insight on the unobservable course of the disease.

North America.

The individual-based simulation model was calibrated leveraging primary data from empirical studies, such as a longitudinal HIV-positive men who have sex with men cohort study [Human Immunodeficiency and Papilloma Virus Research Group (HIPVIRG); n = 247] and the North American AIDS Cohort Collaboration on Research and Design [(NA-ACCORD); n = 13,146]. We used the model to infer unobservable progression probabilities from high-grade precancer to invasive anal cancer by CD4 nadir and human papillomavirus (HPV) genotype.

The calibrated model had good correspondence to data on genotype- and age-specific HPV prevalence; genotype frequency in precancer and cancer; and age- and nadir CD4-specific cancer incidence. The model-projected progression probabilities differed substantially by HPV genotype and nadir CD4 status. For example, among individuals with CD4 nadir <200, the median monthly progression probability from a high-grade lesion to invasive cancer was 0.054% (ie, 6.28% 10-year probability) and 0.004% (ie, 0.48% 10-year probability) for men with an HPV-16 infection versus without a detectable HPV infection, respectively.

We synthesized existing evidence into a state-of-the-art anal cancer disease simulation model that will be used to quantify the tradeoffs of harms and benefits of alternative strategies, understand critical uncertainties, and inform national anal cancer prevention policy.

The incidence of human papillomavirus (HPV)-related cancers has increased (anal cancer) or not declined (cervical cancer) since the introduction of antiretroviral therapy (ART). This article reviews recent data on incidence and prevention efforts for HPV-related cancers in the ART era.

ART may confer some benefit with respect to reducing the risk of anal high-grade squamous intraepithelial lesion and cancer, but the degree of that benefit appears to be limited. The prevalence of anal HPV infection, anal high-grade squamous intraepithelial lesion, and anal cancer remain high among individuals on effective ART. The incidence of cervical cancer is high among HIV-infected women, particularly in countries wherein there are no organized cervical cancer prevention programmes. Efforts are in progress to define optimal screen-and-treat cervical cancer prevention programmes in different clinical settings and to define the efficacy of secondary prevention programmes for prevention of anal cancer.

HPV-related cancers are likely to remain an important problem in HIV-infected men and women for the foreseeable future, even among those on effective ART.

Esophageal cancer (EC) and human immunodeficiency virus (HIV) are common in parts of South Africa. Squamous cell carcinoma of the esophagus in KwaZulu-Natal, South Africa presents generally in advanced stages and is mostly palliated by the deployment of self-expandable metal stent (SEMS). This study analyses these relationships between coexistent HIV infection, SEMS deployment, and survival scores.

Information on patients managed with SEMS between October 2013 and December 2014 was retrieved from a prospective database of EC and followed up until April 2015. Data collected included demographics, HIV status, clinical presentation, prognostic indicators, management, and survival. Prognostic factors were calculated in relation to outcome.

One hundred five patients with EC had median ages of 61 (SD±11.4) and median body mass index of 17.45. Squamous cell carcinoma of the esophagus was diagnosed in 90 patients and adenocancer in 7 patients. Tumors were located in the proximal (10), middle (64), and distal (29) esophagus. Stage IV EC had a significant shorter survival of fewer than 3 months compared with stage III cancer (P=0.009). A C-reactive protein >150 mg/L was 3.6 times more likely to predict survival of fewer than 3 months than a value <50 mg/L (P=0.035). A proximal stent position significantly predicted shorter survival (P=0.035). The Steyerberg prognostic score proved ineffective in predicting survival of <3 months in our setting. Of the 84 patients tested for HIV, 23 were positive. Thirteen patients were on highly active antiretroviral therapy surviving significantly longer than those without this medication (P=0.036).

Stage IV cancer and C-reactive protein >150 predicted survival of <3 months significantly better than the Steyerberg prediction score or other markers. Highly active anti-retroviral therapy had a positive impact on survival; however, SEMS placement in the proximal esophagus was associated with shorter survival.

Infection with certain types of human papillomavirus (HPV) has been associated with the development of cervical and anal cancer. Worldwide, the incidence of anal cancer has increased markedly. The present study aimed to evaluate the prevalence of HPV infection of the uterine cervix and anal canal in human immunodeficiency virus (HIV)- and non-HIV-infected risk populations. Cervical and anal HPV swabs and cytology samples were collected from 287 patients at the University Hospital of Munich, Germany between 2011 and 2013. Patients were divided into HIV-negative controls (G1) and two risk groups, including HIV-negative patients with cytological abnormalities of the cervix (G2) and HIV-infected patients (G3). Data, including clinical parameters, were analysed. The risk groups had significantly more positive results for HPV in the anus (71.03 and 83.15% for G2 and G3, respectively), as compared with G1. The predominant HPV genotypes found in the anus were high-risk HPV genotypes, which were significantly correlated with concomittant cervical HPV findings. In the risk groups, a significant association between the cytological findings and HPV detection in the cervix was found, while the results of the anus revealed no significance. The results of the present study suggested that the prevalence of HPV infection in the anal canal of risk populations is high. Furthermore, patients with abnormal cervical cytology results and HIV-infected women, irrespective of their individual cervical findings, may have a risk of concomittant anal high-risk HPV infection. Based on the predominant HPV genotypes found in the study, HPV vaccination could reduce the incidence of anal cancer. Nevertheless, high-risk patients should be intensively screened for anal squamous intraepithelial abnormalities to avoid invasive cancer stages.

HIV Treatment as Prevention (TasP) initiatives promote antiretroviral therapy (ART) access and optimal adherence (≥95 %) to produce viral suppression among people living with HIV (PLHIV) and prevent the onward transmission of HIV. ART treatment interruptions are common among PLHIV who use drugs and undermine the effectiveness of TasP. Semi-structured interviews were conducted with 39 PLHIV who use drugs who had experienced treatment ART interruptions in a setting with a community-wide TasP initiative (Vancouver, Canada) to examine influences on these outcomes. While study participants attributed ART interruptions to "treatment fatigue," our analysis revealed individual, social, and structural influences on these events, including: (1) prior adverse ART-related experiences among those with long-term treatment histories; (2) experiences of social isolation; and, (3) breakdowns in the continuity of HIV care following disruptive events (e.g., eviction, incarceration). Findings reconceptualise 'treatment fatigue' by focusing attention on its underlying mechanisms, while demonstrating the need for comprehensive structural reforms and targeted interventions to optimize TasP among drug-using PLHIV.

Human papillomavirus (HPV) infections belong to the most common sexually transmitted infections. To date, more than 200 completely classified HPV-types have been reported, and those belonging to the genus alpha predominantly infect the anogenital region. Condylomata acuminata are caused by the two low-risk types HPV6 and HPV11 in more than 90 % of cases. Treatment of genital warts might be either ablative (e.g. electrocautery, surgical excision, or laser therapy) or topical (e.g. podophyllotoxine, trichloroacetic acid, or imiquimod), and depends on the size, location, morphology and anatomical region. Recurrences after treatment are frequent. Therefore, combination therapies (e.g. topical and ablative) play an important role in daily routine. HIV-infected individuals, especially HIV-positive MSM, have a strongly increased risk for anal dysplasia and anal cancer. Condylomata acuminata and a large proportion of anal dysplasia and anal carcinoma are preventable by prophylactic HPV-vaccination.

Squamous cell cancer of the anus (SCCA) is a rare disease of the gastrointestinal tract. Even though chemoradiation therapy is the treatment of choice, a substantial number of patients develop recurrent cancers or present with persisting SCCA. Therefore, abdominoperineal excisions as a salvage therapy are the only chance of cure.

Hospital files of all patients with recurrent squamous cell carcinoma of the anus who underwent abdominoperineal excision performed at the Department of General and Visceral Surgery of the University Hospital Frankfurt between January 2003 and December 2013 were retrospectively reviewed.

Fourteen (nine males, five females) patients underwent abdominoperineal resections for recurrent SCCA. In six patients, the pelvic floor was closed by direct suture, four patients underwent reconstruction using a vertical rectus abdominis myocutaneous (VRAM) flap, and four patients received a gluteal myocutaneous flap. Patients receiving flap-mediated closure revealed a median hospital stay of 26 days (range 13-60 days) compared to 11 days (range 9-30 days) in patients with direct closure (p = 0.01). Two patients (14%) suffered from wound infections (Dindo-Clavien II), whereas three patients (21%) underwent up to seven reoperations for breakdown of their wounds and/or laparotomies (Dindo-Clavien IIIb). The calculated 5-year survival rate was 86%. Patients with rpT0/T1 stage had a significantly longer survival compared to patients presenting with rpT2/T3/T4 tumors.

Abdominoperineal excisions in patients with recurrent SCCA can provide long-term local control and survival. The complication rate is not associated with the closure technique employed, but patients undergoing flap-mediated closure revealed a significantly longer hospital stay.

Anal cancer may be an emerging clinical problem in HIV-infected women particularly in resource-limited settings. Human papillomavirus (HPV) infection is a precursor to anal cancer and is prevalent in HIV-infected women, but the natural history of HPV infection and anal cancer precursors is not well described in this population. It is not known which specific dysplastic lesions in the anus are most likely to progress, and whether treatment of high grade squamous intraepithelial lesion reduces the incidence of anal cancer in women. Cervical HPV infection and associated lesions may be related to the pathogenesis and natural history of anal disease. Cervical screening is resource intensive but some limited infrastructure exists in most areas where cervical cancer is prevalent. Anal screening, however is not performed. It may be that the infrastructure for cervical screening may be leveraged in developing the appropriate research, screening and treatment tools for anal dysplasia.

Persistent oncogenic human papillomavirus (HPV) infection increases the probability that precancerous anal high-grade squamous intraepithelial lesions will progress to invasive anal cancer. Anal neoplasia associated with HPV disproportionately affects HIV-infected individuals, especially men who have sex with men. Prevention is limited to HPV vaccine recommendations, highlighting the need for new treatments. The purpose of this review is to provide HIV information to nurse clinical scientists about HPV-related cancer to highlight the connection between: (a) HPV biology and pathogenesis and (b) the development of drugs and novel therapeutic methods using high-throughput screening. PubMed and CINAHL were used to search the literature to determine HPV-related epidemiology, biology, and use of high-throughput screening for drug discovery. Several events in the HPV life cycle have the potential to be developed into biologic targets for drug discovery using the high-throughput screening technique, which has been successfully used to identify compounds to inhibit HPV infections.