Materiały źródłowe

• #1 Anal Cancer: The Past, Present and Future

  https://www.mdpi.com/1718-7729/30/3/246

  Anal cancer is a rare cancer that accounts for about 2% of all gastrointestinal tract malignancies. Among anal cancer, squamous cell cancer is the most common malignancy. The incidence of all stages of anal squamous cell cancer has been increasing. Human papillomavirus infection and immunosuppression are major risk factors for anal cancer. […] HPV infection is a major risk factor for anal cancer. Sexual behavior and immunosuppression are key drivers of anal cancer risk. HPV is a key risk factor in 80–85% of anal cancer cases; most are associated with HPV16 infections. […] ASCC represents more than 80% of all anal cancer cases. Histological confirmation is vital to eliminate several different and uncommon types of anal cancer. […] SCC of the anal canal primarily develops at the transformation zone between squamous and columnar epithelium. The basement membrane surrounding and within the SCC tumor lacks a myoepithelial layer and presents very similar to skin adnexal and salivary gland neoplasms.

• #2 Anal carcinoma – exploring the epidemiology, risk factors, pathophysiology, diagnosis, and treatment

  https://www.wjgnet.com/2220-315x/full/v14/i3/98525.htm

  Anal carcinoma is a relatively rare tumor that accounts for approximately 2% of gastrointestinal malignancies and less than 7% of anorectal cancers. […] The pathogenesis of anal carcinoma is believed to be linked to human papillomavirus-related inflammation, leading to dysplasia and progression to cancer. […] Integration of HPV double-stranded DNA into the host cell genome facilitates the expression of viral oncoproteins E6 and E7, promoting tumor oncogenesis of anal SCC. […] HPV-related neoplasm requires E6 and E7 expressions to establish and maintain a transformed state. […] This complex interplay serves as the primary mechanism for HPV-related anal SCC. […] HIV-associated anal cancer is believed to be related to microsatellite instability, leading to the progression of invasive carcinoma.

• #3 Anal Carcinoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441891/

  Anal carcinoma is a rare but increasingly prevalent malignancy, with incidence rates rising approximately 2.7% annually over the past decade. Squamous cell carcinoma (SCC) accounts for roughly 85% of cases. […] High-risk human papillomavirus (HPV) infection, particularly types 16 and 18, is the most significant risk factor, with other contributing factors including HIV infection, immunosuppression, smoking, sexual behavior, and older age. […] The pathophysiology of anal SCC is strongly associated with chronic inflammatory processes triggered by persistent HPV infection. HPV preferentially targets the squamocolumnar transition zone within the anal canal, where viral particles infect the basal epithelial cells. This leads to the expression of early viral oncoproteins, eg, E6 and E7, which drive cellular proliferation, disrupt tumor suppressor pathways, and promote malignant transformation. Persistent infection with high-risk HPV serotypes, particularly HPV-16 and HPV-18, is a well-established precursor to anal intraepithelial neoplasia (AIN), a premalignant condition characterized by dysplastic changes in the squamous epithelium. […] Molecular profiling of anal SCC has identified recurrent mutations in the PI3K/AKT/mTOR signaling pathway, as well as alterations in chromatin-modifying genes MLL2 and MLL3, which may contribute to tumor initiation and progression. Additionally, genetic alterations in key tumor suppressor genes, including TP53 and CDKN2A, have been observed, with CDKN2A mutations being more prevalent in HPV-negative tumors, which are associated with worse clinical outcomes.

• #4 Anal Carcinoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441891/

  Anal carcinoma is a rare but increasingly prevalent malignancy, with incidence rates rising approximately 2.7% annually over the past decade. Squamous cell carcinoma (SCC) accounts for roughly 85% of cases. […] High-risk human papillomavirus (HPV) infection, particularly types 16 and 18, is the most significant risk factor, with other contributing factors including HIV infection, immunosuppression, smoking, sexual behavior, and older age. […] The pathophysiology of anal SCC is strongly associated with chronic inflammatory processes triggered by persistent HPV infection. HPV preferentially targets the squamocolumnar transition zone within the anal canal, where viral particles infect the basal epithelial cells. This leads to the expression of early viral oncoproteins, eg, E6 and E7, which drive cellular proliferation, disrupt tumor suppressor pathways, and promote malignant transformation. Persistent infection with high-risk HPV serotypes, particularly HPV-16 and HPV-18, is a well-established precursor to anal intraepithelial neoplasia (AIN), a premalignant condition characterized by dysplastic changes in the squamous epithelium. […] Molecular profiling of anal SCC has identified recurrent mutations in the PI3K/AKT/mTOR signaling pathway, as well as alterations in chromatin-modifying genes MLL2 and MLL3, which may contribute to tumor initiation and progression. Additionally, genetic alterations in key tumor suppressor genes, including TP53 and CDKN2A, have been observed, with CDKN2A mutations being more prevalent in HPV-negative tumors, which are associated with worse clinical outcomes.

• #5 Anal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Anal_cancer

  Anal cancer is typically a squamous cell carcinoma. […] Most anal cancers are squamous cell carcinomas (epidermoid carcinomas), that arises near the squamocolumnar junction. […] Based on the study in Denmark and Sweden, Parkin estimated that 90% of anal cancers are attributable to HPV. […] Epidemiologist Janet Daling, Ph.D., a member of Fred Hutchinson’s Public Health Sciences Division, and her team found that smoking appears to play a significant role in anal-cancer development that is independent of other behavioral risk factors, such as sexual activity. […] The mechanism behind smoking and anal-cancer development is unknown, but researchers speculate that smoking interferes with a process called apoptosis, or programmed cell death, which helps rid the body of abnormal cells that could turn cancerous.

• #6 Anal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Anal_cancer

  Anal cancer is typically a squamous cell carcinoma. […] Most anal cancers are squamous cell carcinomas (epidermoid carcinomas), that arises near the squamocolumnar junction. […] Based on the study in Denmark and Sweden, Parkin estimated that 90% of anal cancers are attributable to HPV. […] Epidemiologist Janet Daling, Ph.D., a member of Fred Hutchinson’s Public Health Sciences Division, and her team found that smoking appears to play a significant role in anal-cancer development that is independent of other behavioral risk factors, such as sexual activity. […] The mechanism behind smoking and anal-cancer development is unknown, but researchers speculate that smoking interferes with a process called apoptosis, or programmed cell death, which helps rid the body of abnormal cells that could turn cancerous.

• #7 Anal Carcinoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441891/

  Anal carcinoma is a rare but increasingly prevalent malignancy, with incidence rates rising approximately 2.7% annually over the past decade. Squamous cell carcinoma (SCC) accounts for roughly 85% of cases. […] High-risk human papillomavirus (HPV) infection, particularly types 16 and 18, is the most significant risk factor, with other contributing factors including HIV infection, immunosuppression, smoking, sexual behavior, and older age. […] The pathophysiology of anal SCC is strongly associated with chronic inflammatory processes triggered by persistent HPV infection. HPV preferentially targets the squamocolumnar transition zone within the anal canal, where viral particles infect the basal epithelial cells. This leads to the expression of early viral oncoproteins, eg, E6 and E7, which drive cellular proliferation, disrupt tumor suppressor pathways, and promote malignant transformation. Persistent infection with high-risk HPV serotypes, particularly HPV-16 and HPV-18, is a well-established precursor to anal intraepithelial neoplasia (AIN), a premalignant condition characterized by dysplastic changes in the squamous epithelium. […] Molecular profiling of anal SCC has identified recurrent mutations in the PI3K/AKT/mTOR signaling pathway, as well as alterations in chromatin-modifying genes MLL2 and MLL3, which may contribute to tumor initiation and progression. Additionally, genetic alterations in key tumor suppressor genes, including TP53 and CDKN2A, have been observed, with CDKN2A mutations being more prevalent in HPV-negative tumors, which are associated with worse clinical outcomes.

• #8 Anal Cancer: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/2500052-overview

  Anal squamous cell cancer is believed to be directly linked to the presence of a complex inflammatory process most commonly caused by HPV infection (particularly with serotypes 16 and 18) in the histologically unique area of the anal squamocolumnar epithelium. In one Scandinavian study, serotype 16 HPV DNA was detected in 73% of anal cancer specimens, and serotype 16, 18, or both was detected in 84% of specimens. In contrast, no rectal cancer specimens contained HPV DNA. […] Active HPV infection affects approximately 10% of women worldwide. The high-risk HPV serotypes 16 and 18, which are responsible for most high-grade intraepithelial lesions that may progress to cancer, along with the low-risk serotypes 6 and 11, were targeted in the widely available quadrivalent HPV vaccine (the current nonavalent HPV vaccine covers serotypes 6, 11, 16, 18, 31, 33, 45, 52, and 58).

• #9 Prevalence of HPV in anal cancer: exploring the role of infection and inflammation | Infectious Agents and Cancer | Full Text

  https://infectagentscancer.biomedcentral.com/articles/10.1186/s13027-024-00624-0

  Anal cancer incidence is rising globally, driven primarily by human papillomavirus (HPV) infection. HPV, especially high-risk types 16 and 18, is considered a necessary cause of anal squamous cell carcinoma. […] Chronic inflammation facilitates viral persistence, cell transformation, and immune evasion through pathways involving the PD-1/PD-L1 axis. […] Understanding these inflammatory processes, including roles of CD8+T cells and PD-1/PD-L1, could guide development of immunotherapies against anal cancer. […] HPV infection is thought to be a required cause of ASCC, which is expected to affect 29,000 people annually, most of whom are women. […] The prevalence of HPV in anal intraepithelial neoplasia (AIN) grades 2 and 3 is even higher, around 94%. […] One of the most important contributing elements to the carcinogenesis of anal squamous cell carcinoma (SCC) is acknowledged to be HPV infection.

• #10 What is HPV Cancer? Symptoms, Causes & Treatment | The Anal Cancer Foundation

  https://www.analcancerfoundation.org/what-is-anal-cancer/hpv-cancer/

  HPV causes a majority of anal cancer (91%) […] HPV types that cause cancer include 16, 18, 31, 33, 34, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68 and 70. Types 16 and 18 are the most common. […] HPV 16 and 18 are the most common and most high-risk types of the virus. Of all cancers probably caused by HPV worldwide, the following are linked to these two specific types: 92% of anal cancer. […] All types of HPV infect squamous epithelial cells, which are the cells that cover the skin and mucous membranes. Once the infection has occurred, the virus is able to enter the cell and make proteins. Two of the proteins made by high-risk types interfere with normal cell functioning that prevents excessive growth. This interference causes the cell to grow uncontrollably. […] If growth continues, lesions (damaged tissue) develop which can eventually turn into tumors (cancer). Researchers believe that it can take from 10 to 20 years or longer for a new infection with high-risk HPV to develop into cancer.

• #11 Anal Cancer: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/2500052-overview

  Anal squamous cell cancer is believed to be directly linked to the presence of a complex inflammatory process most commonly caused by HPV infection (particularly with serotypes 16 and 18) in the histologically unique area of the anal squamocolumnar epithelium. In one Scandinavian study, serotype 16 HPV DNA was detected in 73% of anal cancer specimens, and serotype 16, 18, or both was detected in 84% of specimens. In contrast, no rectal cancer specimens contained HPV DNA. […] Active HPV infection affects approximately 10% of women worldwide. The high-risk HPV serotypes 16 and 18, which are responsible for most high-grade intraepithelial lesions that may progress to cancer, along with the low-risk serotypes 6 and 11, were targeted in the widely available quadrivalent HPV vaccine (the current nonavalent HPV vaccine covers serotypes 6, 11, 16, 18, 31, 33, 45, 52, and 58).

• #12 Anal Carcinoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441891/

  Anal carcinoma is a rare but increasingly prevalent malignancy, with incidence rates rising approximately 2.7% annually over the past decade. Squamous cell carcinoma (SCC) accounts for roughly 85% of cases. […] High-risk human papillomavirus (HPV) infection, particularly types 16 and 18, is the most significant risk factor, with other contributing factors including HIV infection, immunosuppression, smoking, sexual behavior, and older age. […] The pathophysiology of anal SCC is strongly associated with chronic inflammatory processes triggered by persistent HPV infection. HPV preferentially targets the squamocolumnar transition zone within the anal canal, where viral particles infect the basal epithelial cells. This leads to the expression of early viral oncoproteins, eg, E6 and E7, which drive cellular proliferation, disrupt tumor suppressor pathways, and promote malignant transformation. Persistent infection with high-risk HPV serotypes, particularly HPV-16 and HPV-18, is a well-established precursor to anal intraepithelial neoplasia (AIN), a premalignant condition characterized by dysplastic changes in the squamous epithelium. […] Molecular profiling of anal SCC has identified recurrent mutations in the PI3K/AKT/mTOR signaling pathway, as well as alterations in chromatin-modifying genes MLL2 and MLL3, which may contribute to tumor initiation and progression. Additionally, genetic alterations in key tumor suppressor genes, including TP53 and CDKN2A, have been observed, with CDKN2A mutations being more prevalent in HPV-negative tumors, which are associated with worse clinical outcomes.

• #13 Pathology of Anal Cancer – PubMed

  https://pubmed.ncbi.nlm.nih.gov/27889037/

  Anal canal cancer is rather an uncommon disease but its incidence is increasing. […] HPV infection has a key role in precancerous lesions and cancer development by the production of E6 and E7 oncoproteins. […] Currently, there are no biomarkers able to predict prognosis or response to treatment in clinical practice.

• #14 Anal carcinoma – exploring the epidemiology, risk factors, pathophysiology, diagnosis, and treatment

  https://www.wjgnet.com/2220-315x/full/v14/i3/98525.htm

  Anal carcinoma is a relatively rare tumor that accounts for approximately 2% of gastrointestinal malignancies and less than 7% of anorectal cancers. […] The pathogenesis of anal carcinoma is believed to be linked to human papillomavirus-related inflammation, leading to dysplasia and progression to cancer. […] Integration of HPV double-stranded DNA into the host cell genome facilitates the expression of viral oncoproteins E6 and E7, promoting tumor oncogenesis of anal SCC. […] HPV-related neoplasm requires E6 and E7 expressions to establish and maintain a transformed state. […] This complex interplay serves as the primary mechanism for HPV-related anal SCC. […] HIV-associated anal cancer is believed to be related to microsatellite instability, leading to the progression of invasive carcinoma.

• #15 Anal Carcinoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441891/

  Anal carcinoma is a rare but increasingly prevalent malignancy, with incidence rates rising approximately 2.7% annually over the past decade. Squamous cell carcinoma (SCC) accounts for roughly 85% of cases. […] High-risk human papillomavirus (HPV) infection, particularly types 16 and 18, is the most significant risk factor, with other contributing factors including HIV infection, immunosuppression, smoking, sexual behavior, and older age. […] The pathophysiology of anal SCC is strongly associated with chronic inflammatory processes triggered by persistent HPV infection. HPV preferentially targets the squamocolumnar transition zone within the anal canal, where viral particles infect the basal epithelial cells. This leads to the expression of early viral oncoproteins, eg, E6 and E7, which drive cellular proliferation, disrupt tumor suppressor pathways, and promote malignant transformation. Persistent infection with high-risk HPV serotypes, particularly HPV-16 and HPV-18, is a well-established precursor to anal intraepithelial neoplasia (AIN), a premalignant condition characterized by dysplastic changes in the squamous epithelium. […] Molecular profiling of anal SCC has identified recurrent mutations in the PI3K/AKT/mTOR signaling pathway, as well as alterations in chromatin-modifying genes MLL2 and MLL3, which may contribute to tumor initiation and progression. Additionally, genetic alterations in key tumor suppressor genes, including TP53 and CDKN2A, have been observed, with CDKN2A mutations being more prevalent in HPV-negative tumors, which are associated with worse clinical outcomes.

• #16 Anal Carcinoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441891/

  Anal carcinoma is a rare but increasingly prevalent malignancy, with incidence rates rising approximately 2.7% annually over the past decade. Squamous cell carcinoma (SCC) accounts for roughly 85% of cases. […] High-risk human papillomavirus (HPV) infection, particularly types 16 and 18, is the most significant risk factor, with other contributing factors including HIV infection, immunosuppression, smoking, sexual behavior, and older age. […] The pathophysiology of anal SCC is strongly associated with chronic inflammatory processes triggered by persistent HPV infection. HPV preferentially targets the squamocolumnar transition zone within the anal canal, where viral particles infect the basal epithelial cells. This leads to the expression of early viral oncoproteins, eg, E6 and E7, which drive cellular proliferation, disrupt tumor suppressor pathways, and promote malignant transformation. Persistent infection with high-risk HPV serotypes, particularly HPV-16 and HPV-18, is a well-established precursor to anal intraepithelial neoplasia (AIN), a premalignant condition characterized by dysplastic changes in the squamous epithelium. […] Molecular profiling of anal SCC has identified recurrent mutations in the PI3K/AKT/mTOR signaling pathway, as well as alterations in chromatin-modifying genes MLL2 and MLL3, which may contribute to tumor initiation and progression. Additionally, genetic alterations in key tumor suppressor genes, including TP53 and CDKN2A, have been observed, with CDKN2A mutations being more prevalent in HPV-negative tumors, which are associated with worse clinical outcomes.

• #17 Prevalence of HPV in anal cancer: exploring the role of infection and inflammation | Infectious Agents and Cancer | Full Text

  https://infectagentscancer.biomedcentral.com/articles/10.1186/s13027-024-00624-0

  By integrating into the host DNA or remaining as extra-chromosomal epitopes, HPV causes normal squamous anal epithelium to undergo a neoplastic transformation that leads to low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and ultimately squamous cell carcinoma of the anus (SCCA). […] E6 and E7 are two oncoproteins encoded by the HPV genome, whose expression is crucial for the viruss ability to promote cellular proliferation and evade apoptosis in infected cells. […] The interplay between HPV and HIV coinfection complicates the pathogenesis of anal cancer, as HIV can enhance HPVs oncogenic potential by impairing immune responses and epithelial integrity. […] In anal cancer, the chronic inflammatory environment created by HPV and HIV infection facilitates the evasion of apoptosis and immune recognition, allowing tumor cells to proliferate and metastasize.

• #18 Prevalence of HPV in anal cancer: exploring the role of infection and inflammation | Infectious Agents and Cancer | Full Text

  https://infectagentscancer.biomedcentral.com/articles/10.1186/s13027-024-00624-0

  By integrating into the host DNA or remaining as extra-chromosomal epitopes, HPV causes normal squamous anal epithelium to undergo a neoplastic transformation that leads to low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and ultimately squamous cell carcinoma of the anus (SCCA). […] E6 and E7 are two oncoproteins encoded by the HPV genome, whose expression is crucial for the viruss ability to promote cellular proliferation and evade apoptosis in infected cells. […] The interplay between HPV and HIV coinfection complicates the pathogenesis of anal cancer, as HIV can enhance HPVs oncogenic potential by impairing immune responses and epithelial integrity. […] In anal cancer, the chronic inflammatory environment created by HPV and HIV infection facilitates the evasion of apoptosis and immune recognition, allowing tumor cells to proliferate and metastasize.

• #19 Prevalence of HPV in anal cancer: exploring the role of infection and inflammation | Infectious Agents and Cancer | Full Text

  https://infectagentscancer.biomedcentral.com/articles/10.1186/s13027-024-00624-0

  By integrating into the host DNA or remaining as extra-chromosomal epitopes, HPV causes normal squamous anal epithelium to undergo a neoplastic transformation that leads to low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and ultimately squamous cell carcinoma of the anus (SCCA). […] E6 and E7 are two oncoproteins encoded by the HPV genome, whose expression is crucial for the viruss ability to promote cellular proliferation and evade apoptosis in infected cells. […] The interplay between HPV and HIV coinfection complicates the pathogenesis of anal cancer, as HIV can enhance HPVs oncogenic potential by impairing immune responses and epithelial integrity. […] In anal cancer, the chronic inflammatory environment created by HPV and HIV infection facilitates the evasion of apoptosis and immune recognition, allowing tumor cells to proliferate and metastasize.

• #20 Anal carcinoma – exploring the epidemiology, risk factors, pathophysiology, diagnosis, and treatment

  https://www.wjgnet.com/2220-315x/full/v14/i3/98525.htm

  Anal carcinoma is a relatively rare tumor that accounts for approximately 2% of gastrointestinal malignancies and less than 7% of anorectal cancers. […] The pathogenesis of anal carcinoma is believed to be linked to human papillomavirus-related inflammation, leading to dysplasia and progression to cancer. […] Integration of HPV double-stranded DNA into the host cell genome facilitates the expression of viral oncoproteins E6 and E7, promoting tumor oncogenesis of anal SCC. […] HPV-related neoplasm requires E6 and E7 expressions to establish and maintain a transformed state. […] This complex interplay serves as the primary mechanism for HPV-related anal SCC. […] HIV-associated anal cancer is believed to be related to microsatellite instability, leading to the progression of invasive carcinoma.

• #21 Prevalence of HPV in anal cancer: exploring the role of infection and inflammation | Infectious Agents and Cancer | Full Text

  https://infectagentscancer.biomedcentral.com/articles/10.1186/s13027-024-00624-0

  By integrating into the host DNA or remaining as extra-chromosomal epitopes, HPV causes normal squamous anal epithelium to undergo a neoplastic transformation that leads to low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and ultimately squamous cell carcinoma of the anus (SCCA). […] E6 and E7 are two oncoproteins encoded by the HPV genome, whose expression is crucial for the viruss ability to promote cellular proliferation and evade apoptosis in infected cells. […] The interplay between HPV and HIV coinfection complicates the pathogenesis of anal cancer, as HIV can enhance HPVs oncogenic potential by impairing immune responses and epithelial integrity. […] In anal cancer, the chronic inflammatory environment created by HPV and HIV infection facilitates the evasion of apoptosis and immune recognition, allowing tumor cells to proliferate and metastasize.

• #22 Anal squamous cell carcinoma: An evolution in disease and management

  https://www.wjgnet.com/1007-9327/full/v20/i36/13052.htm

  Anal squamous cell carcinoma is thought to arise from a precursor lesion termed anal intraepithelial neoplasia (AIN) (Figure 3). AIN is a histologic, as opposed to cytologic, diagnosis with varying degrees of dysplasia. AINI, II, and III have low, medium, and high grades of dysplasia respectively. […] The natural history of AIN continues to be studied. Progression of low grades of AIN to high grade in HIV positive MSM or bisexual men is 62% at two years. Progression of AIN to anal cancer will happen in 10% of cases with at least one year follow up. […] We are currently are in the midst of another major shift in the treatment of anal cancer. Basic science and translational research have led to the identification of the virus which causes most cases of anal cancer and to a vaccine that can help prevent precursor lesions as well as tools to screen and treat high risk individuals. Current efforts are extending beyond treatment to screening and prevention.

• #23 Anal Cancer: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/2500052-overview

  Anal cancer research has adopted terminology that mirrors the grading of cervical dysplasia (ie, cervical intraepithelial neoplasia grades I, II, and III). Anal intraepithelial neoplasia (AIN) grade I is low-grade dysplasia (LGAIN), while AIN-II and AIN-III are high-grade dysplasia (HGAIN), which is then thought to progress to invasive cancer, as in the cervical model. The grading system takes into account histological attributes that include the following: abnormalities in differentiation and maturation of the squamous layers, the depth of those abnormalities, mitotic activity, and nuclear membrane changes. […] Progression of AIN to invasive cancer of the anus has been shown to occur in 10-11% of cases. […] HIV-positive individuals have higher rates of conversion, even if their HIV disease is under control and despite lack of progression to AIDS.

• #24 Anal Cancer | Concise Medical Knowledge

  https://www.lecturio.com/concepts/anal-cancer/

  Anal cancer accounts for 2.7% of all gastrointestinal tract cancers. Squamous Cell Carcinoma (SCC) is the most common type of anal cancer. The diagnosis is established via biopsy and pathologic examination of specimens from the living body. Carcinogenesis of anal SCC: Inflammatory response of the anal epithelium develops most commonly as a response to infection by HPV. Inflammation progresses to the development of anal intraepithelia neoplasia (AIN): AIN 1: corresponds to low-grade squamous epithelial lesion (LSIL); AIN 2 and 3: high-grade SIL (HSIL); pre-malignant; HSIL can progress to invasive SCC. The progression to invasive cancer is promoted by HIV/immunosuppression and other risk factors (multiple HPV types, high-risk sexual behavior). Tumors arising from the transitional and squamous mucosa: squamous cell carcinoma. Tumors arising from the keratinizing squamous area and skin: perianal skin cancers, often SCC (same treatment approach as anal canal cancers).

• #25 Anal Cancer: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/2500052-overview

  Anal cancer research has adopted terminology that mirrors the grading of cervical dysplasia (ie, cervical intraepithelial neoplasia grades I, II, and III). Anal intraepithelial neoplasia (AIN) grade I is low-grade dysplasia (LGAIN), while AIN-II and AIN-III are high-grade dysplasia (HGAIN), which is then thought to progress to invasive cancer, as in the cervical model. The grading system takes into account histological attributes that include the following: abnormalities in differentiation and maturation of the squamous layers, the depth of those abnormalities, mitotic activity, and nuclear membrane changes. […] Progression of AIN to invasive cancer of the anus has been shown to occur in 10-11% of cases. […] HIV-positive individuals have higher rates of conversion, even if their HIV disease is under control and despite lack of progression to AIDS.

• #26 Anal Cancer: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/2500052-overview

  Anal cancer research has adopted terminology that mirrors the grading of cervical dysplasia (ie, cervical intraepithelial neoplasia grades I, II, and III). Anal intraepithelial neoplasia (AIN) grade I is low-grade dysplasia (LGAIN), while AIN-II and AIN-III are high-grade dysplasia (HGAIN), which is then thought to progress to invasive cancer, as in the cervical model. The grading system takes into account histological attributes that include the following: abnormalities in differentiation and maturation of the squamous layers, the depth of those abnormalities, mitotic activity, and nuclear membrane changes. […] Progression of AIN to invasive cancer of the anus has been shown to occur in 10-11% of cases. […] HIV-positive individuals have higher rates of conversion, even if their HIV disease is under control and despite lack of progression to AIDS.

• #27 Anal Cancer: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/2500052-overview

  Anal cancer research has adopted terminology that mirrors the grading of cervical dysplasia (ie, cervical intraepithelial neoplasia grades I, II, and III). Anal intraepithelial neoplasia (AIN) grade I is low-grade dysplasia (LGAIN), while AIN-II and AIN-III are high-grade dysplasia (HGAIN), which is then thought to progress to invasive cancer, as in the cervical model. The grading system takes into account histological attributes that include the following: abnormalities in differentiation and maturation of the squamous layers, the depth of those abnormalities, mitotic activity, and nuclear membrane changes. […] Progression of AIN to invasive cancer of the anus has been shown to occur in 10-11% of cases. […] HIV-positive individuals have higher rates of conversion, even if their HIV disease is under control and despite lack of progression to AIDS.

• #28 Anal squamous cell carcinoma: An evolution in disease and management

  https://www.wjgnet.com/1007-9327/full/v20/i36/13052.htm

  Anal squamous cell carcinoma is thought to arise from a precursor lesion termed anal intraepithelial neoplasia (AIN) (Figure 3). AIN is a histologic, as opposed to cytologic, diagnosis with varying degrees of dysplasia. AINI, II, and III have low, medium, and high grades of dysplasia respectively. […] The natural history of AIN continues to be studied. Progression of low grades of AIN to high grade in HIV positive MSM or bisexual men is 62% at two years. Progression of AIN to anal cancer will happen in 10% of cases with at least one year follow up. […] We are currently are in the midst of another major shift in the treatment of anal cancer. Basic science and translational research have led to the identification of the virus which causes most cases of anal cancer and to a vaccine that can help prevent precursor lesions as well as tools to screen and treat high risk individuals. Current efforts are extending beyond treatment to screening and prevention.

• #29 Anal Cancer: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/2500052-overview

  Anal cancer research has adopted terminology that mirrors the grading of cervical dysplasia (ie, cervical intraepithelial neoplasia grades I, II, and III). Anal intraepithelial neoplasia (AIN) grade I is low-grade dysplasia (LGAIN), while AIN-II and AIN-III are high-grade dysplasia (HGAIN), which is then thought to progress to invasive cancer, as in the cervical model. The grading system takes into account histological attributes that include the following: abnormalities in differentiation and maturation of the squamous layers, the depth of those abnormalities, mitotic activity, and nuclear membrane changes. […] Progression of AIN to invasive cancer of the anus has been shown to occur in 10-11% of cases. […] HIV-positive individuals have higher rates of conversion, even if their HIV disease is under control and despite lack of progression to AIDS.

• #30 Anal Carcinoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441891/

  Anal carcinoma is a rare but increasingly prevalent malignancy, with incidence rates rising approximately 2.7% annually over the past decade. Squamous cell carcinoma (SCC) accounts for roughly 85% of cases. […] High-risk human papillomavirus (HPV) infection, particularly types 16 and 18, is the most significant risk factor, with other contributing factors including HIV infection, immunosuppression, smoking, sexual behavior, and older age. […] The pathophysiology of anal SCC is strongly associated with chronic inflammatory processes triggered by persistent HPV infection. HPV preferentially targets the squamocolumnar transition zone within the anal canal, where viral particles infect the basal epithelial cells. This leads to the expression of early viral oncoproteins, eg, E6 and E7, which drive cellular proliferation, disrupt tumor suppressor pathways, and promote malignant transformation. Persistent infection with high-risk HPV serotypes, particularly HPV-16 and HPV-18, is a well-established precursor to anal intraepithelial neoplasia (AIN), a premalignant condition characterized by dysplastic changes in the squamous epithelium. […] Molecular profiling of anal SCC has identified recurrent mutations in the PI3K/AKT/mTOR signaling pathway, as well as alterations in chromatin-modifying genes MLL2 and MLL3, which may contribute to tumor initiation and progression. Additionally, genetic alterations in key tumor suppressor genes, including TP53 and CDKN2A, have been observed, with CDKN2A mutations being more prevalent in HPV-negative tumors, which are associated with worse clinical outcomes.

• #31 Anal Cancer: The Past, Present and Future

  https://www.mdpi.com/1718-7729/30/3/246

  Gene expression profiling of ASCC has shown that mutations in phosphoinositol-3-kinase pathway-related genes (PI3K/AKT/mammalian target of rapamycin [mTOR]), MLL2, and MLL3 are relatively common along with differential expression of genes in relation to HPV infection. Mutations in the tumor suppressor genes TP53 and CDKN2A correlate significantly with HPV-negative cases. […] Overall, the management of anal cancer has seen advances over the last two decades. However, CRT with 5FU and MMC has remained the current standard therapy for early and locally advanced disease. The role of targeted or immunotherapy in combination with CRT or alone is currently not known. […] Despite treatment advances for anal cancer, there are several knowledge gaps in the management of both early and advanced anal cancer. Research directed at prevention is important to reduce the rising burden of ASCC.

• #32 Anal Carcinoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441891/

  Anal carcinoma is a rare but increasingly prevalent malignancy, with incidence rates rising approximately 2.7% annually over the past decade. Squamous cell carcinoma (SCC) accounts for roughly 85% of cases. […] High-risk human papillomavirus (HPV) infection, particularly types 16 and 18, is the most significant risk factor, with other contributing factors including HIV infection, immunosuppression, smoking, sexual behavior, and older age. […] The pathophysiology of anal SCC is strongly associated with chronic inflammatory processes triggered by persistent HPV infection. HPV preferentially targets the squamocolumnar transition zone within the anal canal, where viral particles infect the basal epithelial cells. This leads to the expression of early viral oncoproteins, eg, E6 and E7, which drive cellular proliferation, disrupt tumor suppressor pathways, and promote malignant transformation. Persistent infection with high-risk HPV serotypes, particularly HPV-16 and HPV-18, is a well-established precursor to anal intraepithelial neoplasia (AIN), a premalignant condition characterized by dysplastic changes in the squamous epithelium. […] Molecular profiling of anal SCC has identified recurrent mutations in the PI3K/AKT/mTOR signaling pathway, as well as alterations in chromatin-modifying genes MLL2 and MLL3, which may contribute to tumor initiation and progression. Additionally, genetic alterations in key tumor suppressor genes, including TP53 and CDKN2A, have been observed, with CDKN2A mutations being more prevalent in HPV-negative tumors, which are associated with worse clinical outcomes.

• #33 Anal Cancer: The Past, Present and Future

  https://www.mdpi.com/1718-7729/30/3/246

  Gene expression profiling of ASCC has shown that mutations in phosphoinositol-3-kinase pathway-related genes (PI3K/AKT/mammalian target of rapamycin [mTOR]), MLL2, and MLL3 are relatively common along with differential expression of genes in relation to HPV infection. Mutations in the tumor suppressor genes TP53 and CDKN2A correlate significantly with HPV-negative cases. […] Overall, the management of anal cancer has seen advances over the last two decades. However, CRT with 5FU and MMC has remained the current standard therapy for early and locally advanced disease. The role of targeted or immunotherapy in combination with CRT or alone is currently not known. […] Despite treatment advances for anal cancer, there are several knowledge gaps in the management of both early and advanced anal cancer. Research directed at prevention is important to reduce the rising burden of ASCC.

• #34 Inflammatory pathways confer resistance to chemoradiotherapy in anal squamous cell carcinoma | npj Precision Oncology

  https://www.nature.com/articles/s41698-024-00585-y

  Anal squamous cell carcinoma (ASCC) is associated with immunosuppression and infection with human papillomavirus (HPV). […] A comprehensive molecular characterization of CRT resistance is lacking, and little is known about the interplay between tumor immune contexture, host immunity, and immunosuppressive and/or immune activating effects of CRT. […] Gene set enrichment analysis showed that pathways for IFN, IFN, inflammatory response, TNF signaling via NF-B, and EMT were significantly enriched in poor responders (all p<0.001). [...] Inflammatory pathways in tissue in line with elevated levels of regulatory T-cells and CXCL2 in peripheral blood are associated with resistance to CRT. [...] We here showed that the interferon-induced transmembrane protein 1 (IFITM1) is an adverse prognostic factor for FFLF and FFDM in ASCC, both on mRNA and protein expression levels, and acts independently of established prognostic factors like T-stage and N-stage.

• #35 The Role of Inflammation in Anal Cancer

  https://www.mdpi.com/2079-9721/10/2/27

  The aim of this article was to present a summary of the current resources available in the literature regarding the role of inflammation in anal cancer development. […] The importance of understanding the pathogenesis and risk factors for anal cancer has been recognized over the last several decades due to an increase in incidence that has been noticed worldwide. […] It is well established that a complex inflammatory response to infection plays a significant role in tumorigenesis. […] Chronic inflammation has been associated with different pathophysiological mechanisms that lead to cellular transformation and several changes in immunological response, allowing tumor cells to avoid apoptosis and immune surveillance. […] The association between inflammation and cancer development is widely accepted, and this review highlights the role of inflammatory processes caused by HPV infection, HIV infection, HPV and HIV coinfection, and inflammatory bowel diseases in anal cancer development.

• #36 The Role of Inflammation in Anal Cancer

  https://www.mdpi.com/2079-9721/10/2/27

  The aim of this article was to present a summary of the current resources available in the literature regarding the role of inflammation in anal cancer development. […] The importance of understanding the pathogenesis and risk factors for anal cancer has been recognized over the last several decades due to an increase in incidence that has been noticed worldwide. […] It is well established that a complex inflammatory response to infection plays a significant role in tumorigenesis. […] Chronic inflammation has been associated with different pathophysiological mechanisms that lead to cellular transformation and several changes in immunological response, allowing tumor cells to avoid apoptosis and immune surveillance. […] The association between inflammation and cancer development is widely accepted, and this review highlights the role of inflammatory processes caused by HPV infection, HIV infection, HPV and HIV coinfection, and inflammatory bowel diseases in anal cancer development.

• #37 Epidemiology and Pathogenesis of Anal Cancer | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-030-20253-8_2

  Anal squamous cell carcinoma (SCC) is a relatively rare malignancy that in most cases is related to chronic infection from the human papillomavirus (HPV). […] The association with HPV infection places certain groups at high risk of developing precursor anal intraepithelial lesions and invasive cancer, including patients with chronic immunosuppression from human immunodeficiency virus (HIV) or other etiologies. […] This chapter will discuss the incidence of anal SCC and how it has changed over time, risk factors for the development of invasive cancer, the pathogenesis of anal SCC, and the screening programs and treatment modalities available for anal dysplasia.

• #38 Epidemiology and Pathogenesis of Anal Cancer | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-030-20253-8_2

  Anal squamous cell carcinoma (SCC) is a relatively rare malignancy that in most cases is related to chronic infection from the human papillomavirus (HPV). […] The association with HPV infection places certain groups at high risk of developing precursor anal intraepithelial lesions and invasive cancer, including patients with chronic immunosuppression from human immunodeficiency virus (HIV) or other etiologies. […] This chapter will discuss the incidence of anal SCC and how it has changed over time, risk factors for the development of invasive cancer, the pathogenesis of anal SCC, and the screening programs and treatment modalities available for anal dysplasia.

• #39 Anal Cancer | Oncohema Key

  https://oncohemakey.com/anal-cancer/

  Therefore, HPV appears to be found in the vast majority of anal cancers. […] The presence of HPV also has been reported to be a positive prognostic biomarker for patients with nonmetastatic SCC of the anal canal. […] Although a direct relationship between HIV and carcinoma of the anal canal has not been clearly established, a strong correlation exists between HIV and HPV. […] Solid organ transplantation has been associated with a 10-fold increased risk of developing anal cancer and a 20-fold increased risk for vulvar and vaginal cancers. […] Prior case-control studies have indicated that chronic tobacco use may result in a two- to five-fold increased likelihood of developing anal cancer.

• #40

  https://journals.lww.com/jaids/abstract/2016/01001/a_109_pathogenesis_of_anal_cancer.15.aspx

  Although the risk of anal cancer is increased among HIV-negative men who have sex with men (MSM) compared with the general population, HIV clearly adds to that risk. […] Anal cancer is very similar biologically to cervical cancer. […] There are likely to be several mechanisms by which HIV infection contributes to the increased risk of anal cancer including: attenuation of systemic immune response with reduced cell mediated immune response to HPV antigens; local immune response perturbation in the form of chronic HIV-induced low-level tissue inflammation; direct interactions between HIV proteins and HPV within the epithelium including reduction of epithelial tight junction integrity due to tat and gp120, with increased risk of HPV infection due to tat and gp120; and up-regulation of HPV oncogene expression by tat. […] With evidence for epithelium as a potential reservoir of HIV infection, HIV-HPV interactions may continue despite good HIV control on ART, and may explain in part the lack of impact of ART in reducing the incidence of anal cancer in HIV-infected individuals.

• #41

  https://journals.lww.com/jaids/abstract/2016/01001/a_109_pathogenesis_of_anal_cancer.15.aspx

  Although the risk of anal cancer is increased among HIV-negative men who have sex with men (MSM) compared with the general population, HIV clearly adds to that risk. […] Anal cancer is very similar biologically to cervical cancer. […] There are likely to be several mechanisms by which HIV infection contributes to the increased risk of anal cancer including: attenuation of systemic immune response with reduced cell mediated immune response to HPV antigens; local immune response perturbation in the form of chronic HIV-induced low-level tissue inflammation; direct interactions between HIV proteins and HPV within the epithelium including reduction of epithelial tight junction integrity due to tat and gp120, with increased risk of HPV infection due to tat and gp120; and up-regulation of HPV oncogene expression by tat. […] With evidence for epithelium as a potential reservoir of HIV infection, HIV-HPV interactions may continue despite good HIV control on ART, and may explain in part the lack of impact of ART in reducing the incidence of anal cancer in HIV-infected individuals.

• #42

  https://journals.lww.com/jaids/abstract/2016/01001/a_109_pathogenesis_of_anal_cancer.15.aspx

  Although the risk of anal cancer is increased among HIV-negative men who have sex with men (MSM) compared with the general population, HIV clearly adds to that risk. […] Anal cancer is very similar biologically to cervical cancer. […] There are likely to be several mechanisms by which HIV infection contributes to the increased risk of anal cancer including: attenuation of systemic immune response with reduced cell mediated immune response to HPV antigens; local immune response perturbation in the form of chronic HIV-induced low-level tissue inflammation; direct interactions between HIV proteins and HPV within the epithelium including reduction of epithelial tight junction integrity due to tat and gp120, with increased risk of HPV infection due to tat and gp120; and up-regulation of HPV oncogene expression by tat. […] With evidence for epithelium as a potential reservoir of HIV infection, HIV-HPV interactions may continue despite good HIV control on ART, and may explain in part the lack of impact of ART in reducing the incidence of anal cancer in HIV-infected individuals.

• #43

  https://journals.lww.com/jaids/abstract/2016/01001/a_109_pathogenesis_of_anal_cancer.15.aspx

  Although the risk of anal cancer is increased among HIV-negative men who have sex with men (MSM) compared with the general population, HIV clearly adds to that risk. […] Anal cancer is very similar biologically to cervical cancer. […] There are likely to be several mechanisms by which HIV infection contributes to the increased risk of anal cancer including: attenuation of systemic immune response with reduced cell mediated immune response to HPV antigens; local immune response perturbation in the form of chronic HIV-induced low-level tissue inflammation; direct interactions between HIV proteins and HPV within the epithelium including reduction of epithelial tight junction integrity due to tat and gp120, with increased risk of HPV infection due to tat and gp120; and up-regulation of HPV oncogene expression by tat. […] With evidence for epithelium as a potential reservoir of HIV infection, HIV-HPV interactions may continue despite good HIV control on ART, and may explain in part the lack of impact of ART in reducing the incidence of anal cancer in HIV-infected individuals.

• #44

  https://journals.lww.com/jaids/abstract/2016/01001/a_109_pathogenesis_of_anal_cancer.15.aspx

  Although the risk of anal cancer is increased among HIV-negative men who have sex with men (MSM) compared with the general population, HIV clearly adds to that risk. […] Anal cancer is very similar biologically to cervical cancer. […] There are likely to be several mechanisms by which HIV infection contributes to the increased risk of anal cancer including: attenuation of systemic immune response with reduced cell mediated immune response to HPV antigens; local immune response perturbation in the form of chronic HIV-induced low-level tissue inflammation; direct interactions between HIV proteins and HPV within the epithelium including reduction of epithelial tight junction integrity due to tat and gp120, with increased risk of HPV infection due to tat and gp120; and up-regulation of HPV oncogene expression by tat. […] With evidence for epithelium as a potential reservoir of HIV infection, HIV-HPV interactions may continue despite good HIV control on ART, and may explain in part the lack of impact of ART in reducing the incidence of anal cancer in HIV-infected individuals.

• #45

  https://journals.lww.com/jaids/abstract/2016/01001/a_109_pathogenesis_of_anal_cancer.15.aspx

  Although the risk of anal cancer is increased among HIV-negative men who have sex with men (MSM) compared with the general population, HIV clearly adds to that risk. […] Anal cancer is very similar biologically to cervical cancer. […] There are likely to be several mechanisms by which HIV infection contributes to the increased risk of anal cancer including: attenuation of systemic immune response with reduced cell mediated immune response to HPV antigens; local immune response perturbation in the form of chronic HIV-induced low-level tissue inflammation; direct interactions between HIV proteins and HPV within the epithelium including reduction of epithelial tight junction integrity due to tat and gp120, with increased risk of HPV infection due to tat and gp120; and up-regulation of HPV oncogene expression by tat. […] With evidence for epithelium as a potential reservoir of HIV infection, HIV-HPV interactions may continue despite good HIV control on ART, and may explain in part the lack of impact of ART in reducing the incidence of anal cancer in HIV-infected individuals.

• #46 Anal Cancer | Oncohema Key

  https://oncohemakey.com/anal-cancer/

  Therefore, HPV appears to be found in the vast majority of anal cancers. […] The presence of HPV also has been reported to be a positive prognostic biomarker for patients with nonmetastatic SCC of the anal canal. […] Although a direct relationship between HIV and carcinoma of the anal canal has not been clearly established, a strong correlation exists between HIV and HPV. […] Solid organ transplantation has been associated with a 10-fold increased risk of developing anal cancer and a 20-fold increased risk for vulvar and vaginal cancers. […] Prior case-control studies have indicated that chronic tobacco use may result in a two- to five-fold increased likelihood of developing anal cancer.

• #47 HPV infection, anal intra-epithelial neoplasia (AIN) and anal cancer: current issues | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-12-398

  Progression of AIN to anal SCC has been assessed in small studies with surveillance and treatment, but with a relatively short follow up of 510years. […] The authors suggest that immunosuppressed patients (6 in this study all from long term oral therapy, such as corticosteroids, for various conditions) and those with multifocal AIN (7 in this study) are at higher risk of malignant transformation. […] However, a recent meta-analysis has indicated that progression rates from HGAIN to anal cancer are approximately one in 600 per year in HIV-positive MSM and one in 4000 per year in HIV-negative MSM patients, substantially lower than the one in 80 per year observed in comparable cervical disease. […] There are strong supportive data for the contention that HGAIN is a precursor lesion to invasive anal carcinoma. […] There is now a need for multi-centre prospective studies on progression of AIN 3 to cancer and on the effectiveness of treatment to reduce the incidence of anal cancer.

• #48 Prevalence of HPV in anal cancer: exploring the role of infection and inflammation | Infectious Agents and Cancer | Full Text

  https://infectagentscancer.biomedcentral.com/articles/10.1186/s13027-024-00624-0

  Several pro-inflammatory pathways are involved in this process, notably the NF-B signaling pathway. […] The PD-1/PD-L1 pathway appears to play a central role in suppressing anti-tumor immunity. […] A deeper understanding of how HIV, HPV, and inflammation coordinately disrupt CD8+T cell responses and promote oncogene expression could reveal new therapeutic targets. […] Immunotherapies blocking the PD-1/PD-L1 axis show promise, but further research is needed on optimizing these approaches based on each patients viral, inflammatory and immune status.

• #49 Prevalence of HPV in anal cancer: exploring the role of infection and inflammation | Infectious Agents and Cancer | Full Text

  https://infectagentscancer.biomedcentral.com/articles/10.1186/s13027-024-00624-0

  Several pro-inflammatory pathways are involved in this process, notably the NF-B signaling pathway. […] The PD-1/PD-L1 pathway appears to play a central role in suppressing anti-tumor immunity. […] A deeper understanding of how HIV, HPV, and inflammation coordinately disrupt CD8+T cell responses and promote oncogene expression could reveal new therapeutic targets. […] Immunotherapies blocking the PD-1/PD-L1 axis show promise, but further research is needed on optimizing these approaches based on each patients viral, inflammatory and immune status.

• #50 Prevalence of HPV in anal cancer: exploring the role of infection and inflammation | Infectious Agents and Cancer | Full Text

  https://infectagentscancer.biomedcentral.com/articles/10.1186/s13027-024-00624-0

  Several pro-inflammatory pathways are involved in this process, notably the NF-B signaling pathway. […] The PD-1/PD-L1 pathway appears to play a central role in suppressing anti-tumor immunity. […] A deeper understanding of how HIV, HPV, and inflammation coordinately disrupt CD8+T cell responses and promote oncogene expression could reveal new therapeutic targets. […] Immunotherapies blocking the PD-1/PD-L1 axis show promise, but further research is needed on optimizing these approaches based on each patients viral, inflammatory and immune status.

• #51 Inflammatory pathways confer resistance to chemoradiotherapy in anal squamous cell carcinoma | npj Precision Oncology

  https://www.nature.com/articles/s41698-024-00585-y

  Anal squamous cell carcinoma (ASCC) is associated with immunosuppression and infection with human papillomavirus (HPV). […] A comprehensive molecular characterization of CRT resistance is lacking, and little is known about the interplay between tumor immune contexture, host immunity, and immunosuppressive and/or immune activating effects of CRT. […] Gene set enrichment analysis showed that pathways for IFN, IFN, inflammatory response, TNF signaling via NF-B, and EMT were significantly enriched in poor responders (all p<0.001). [...] Inflammatory pathways in tissue in line with elevated levels of regulatory T-cells and CXCL2 in peripheral blood are associated with resistance to CRT. [...] We here showed that the interferon-induced transmembrane protein 1 (IFITM1) is an adverse prognostic factor for FFLF and FFDM in ASCC, both on mRNA and protein expression levels, and acts independently of established prognostic factors like T-stage and N-stage.

• #52 Inflammatory pathways confer resistance to chemoradiotherapy in anal squamous cell carcinoma | npj Precision Oncology

  https://www.nature.com/articles/s41698-024-00585-y

  The molecular mechanism of IFITM 1 in cancer generally remains poorly examined, but may include, among others, regulation of matrix metalloproteinases, caveolin-1, and other proteins associated with cell migration and adhesion. […] CXCL2, a neutrophil chemo-attractant that is involved in chronic inflammation and tumor progression, was identified as negative prognostic factor after CRT in peripheral blood. […] This study has several limitations. […] Despite the novelty of the findings, more detailed mechanistic insight is lacking, mainly due to the lack of preclinical in vitro and in vivo models of ASCC. […] In conclusion, we found that chronic inflammatory pathways in tumor tissue, as measured by RNA sequencing (IFN; IFN, TNF signaling via NF-B, IFITM1) and immunohistochemistry (IFITM1, PD-L1, CD8+TIL), in line with elevated levels of regulatory T-cells and CXCL2 in peripheral blood, are associated with CRT resistance and poor prognosis in ASCC.

• #53 Inflammatory pathways confer resistance to chemoradiotherapy in anal squamous cell carcinoma | npj Precision Oncology

  https://www.nature.com/articles/s41698-024-00585-y

  The molecular mechanism of IFITM 1 in cancer generally remains poorly examined, but may include, among others, regulation of matrix metalloproteinases, caveolin-1, and other proteins associated with cell migration and adhesion. […] CXCL2, a neutrophil chemo-attractant that is involved in chronic inflammation and tumor progression, was identified as negative prognostic factor after CRT in peripheral blood. […] This study has several limitations. […] Despite the novelty of the findings, more detailed mechanistic insight is lacking, mainly due to the lack of preclinical in vitro and in vivo models of ASCC. […] In conclusion, we found that chronic inflammatory pathways in tumor tissue, as measured by RNA sequencing (IFN; IFN, TNF signaling via NF-B, IFITM1) and immunohistochemistry (IFITM1, PD-L1, CD8+TIL), in line with elevated levels of regulatory T-cells and CXCL2 in peripheral blood, are associated with CRT resistance and poor prognosis in ASCC.

• #54 The Microbiome and Anal Cancer Pathogenesis in HIV-infected Men who have Sex with Men – Joel Palefsky

  https://grantome.com/grant/NIH/R03-CA203589-01A1

  The risk of anal cancer in HIV-infected individuals has markedly increased following the advent of anti-retroviral therapy, especially in HIV-infected men who have sex with men (MSM). 90% percent of invasive anal squamous cell carcinomas are associated with human papillomavirus (HPV) infection, of which 80-90% are associated with HPV type 16. […] Recent advances in technology have made it feasible to sequence and study the genetic composition, or ?microbiome?, of the community of microbes that colonize different parts of the human body. The expansion of otherwise commensal bacteria within the gastrointestinal tract is postulated to contribute to inflammation and carcinogenesis via a variety of pathways including the production of superoxide radicals and toxins. […] This study will determine whether a similar association exists between the anal canal microbiome and high-grade squamous intraepithelial lesions (HSIL), the precursor to invasive anal cancer.

• #55 The Microbiome and Anal Cancer Pathogenesis in HIV-infected Men who have Sex with Men – Joel Palefsky

  https://grantome.com/grant/NIH/R03-CA203589-01A1

  The risk of anal cancer in HIV-infected individuals has markedly increased following the advent of anti-retroviral therapy, especially in HIV-infected men who have sex with men (MSM). 90% percent of invasive anal squamous cell carcinomas are associated with human papillomavirus (HPV) infection, of which 80-90% are associated with HPV type 16. […] Recent advances in technology have made it feasible to sequence and study the genetic composition, or ?microbiome?, of the community of microbes that colonize different parts of the human body. The expansion of otherwise commensal bacteria within the gastrointestinal tract is postulated to contribute to inflammation and carcinogenesis via a variety of pathways including the production of superoxide radicals and toxins. […] This study will determine whether a similar association exists between the anal canal microbiome and high-grade squamous intraepithelial lesions (HSIL), the precursor to invasive anal cancer.

• #56 The Microbiome and Anal Cancer Pathogenesis in HIV-infected Men who have Sex with Men – Joel Palefsky

  https://grantome.com/grant/NIH/R03-CA203589-01A1

  The risk of anal cancer in HIV-infected individuals has markedly increased following the advent of anti-retroviral therapy, especially in HIV-infected men who have sex with men (MSM). 90% percent of invasive anal squamous cell carcinomas are associated with human papillomavirus (HPV) infection, of which 80-90% are associated with HPV type 16. […] Recent advances in technology have made it feasible to sequence and study the genetic composition, or ?microbiome?, of the community of microbes that colonize different parts of the human body. The expansion of otherwise commensal bacteria within the gastrointestinal tract is postulated to contribute to inflammation and carcinogenesis via a variety of pathways including the production of superoxide radicals and toxins. […] This study will determine whether a similar association exists between the anal canal microbiome and high-grade squamous intraepithelial lesions (HSIL), the precursor to invasive anal cancer.

• #57 The Microbiome and Anal Cancer Pathogenesis in HIV-infected Men who have Sex with Men – Joel Palefsky

  https://grantome.com/grant/NIH/R03-CA203589-01A1

  Our results will contribute to our understanding of HPV carcinogenesis and may potentially provide new approaches to diagnosis and treatment of anal HSIL. […] Because alterations to the bacterial composition of the gastrointestinal tract are linked to colorectal cancer and inflammatory bowel disease, we will determine whether a similar imbalance within the anal canal is associated with development of anal cancer precursors in HIV-infected MSM.

• #58 Anal Carcinoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK441891/

  Anal carcinoma is a rare but increasingly prevalent malignancy, with incidence rates rising approximately 2.7% annually over the past decade. Squamous cell carcinoma (SCC) accounts for roughly 85% of cases. […] High-risk human papillomavirus (HPV) infection, particularly types 16 and 18, is the most significant risk factor, with other contributing factors including HIV infection, immunosuppression, smoking, sexual behavior, and older age. […] The pathophysiology of anal SCC is strongly associated with chronic inflammatory processes triggered by persistent HPV infection. HPV preferentially targets the squamocolumnar transition zone within the anal canal, where viral particles infect the basal epithelial cells. This leads to the expression of early viral oncoproteins, eg, E6 and E7, which drive cellular proliferation, disrupt tumor suppressor pathways, and promote malignant transformation. Persistent infection with high-risk HPV serotypes, particularly HPV-16 and HPV-18, is a well-established precursor to anal intraepithelial neoplasia (AIN), a premalignant condition characterized by dysplastic changes in the squamous epithelium. […] Molecular profiling of anal SCC has identified recurrent mutations in the PI3K/AKT/mTOR signaling pathway, as well as alterations in chromatin-modifying genes MLL2 and MLL3, which may contribute to tumor initiation and progression. Additionally, genetic alterations in key tumor suppressor genes, including TP53 and CDKN2A, have been observed, with CDKN2A mutations being more prevalent in HPV-negative tumors, which are associated with worse clinical outcomes.

• #59 Lifestyle links to anal cancer | Fred Hutchinson Cancer Center

  https://www.fredhutch.org/en/news/center-news/2004/07/anal-cancer.html

  Anal cancer is on the rise in both sexes, particularly among American men, and changing trends in sexual behavior along with current tobacco use and infection by a specific strain of the human papillomavirus may help explain the increase. […] The second study, led by PHS investigator Dr. Janet Daling, set out to better understand the underlying biological and lifestyle causes behind the rising incidence of anal cancer. […] „We found that infection with HPV is necessary in most if not all cases of anal cancer, as close to 90 percent of the tumors studied were positive for the virus,” said Daling, a pioneer in studying the link between HPV and anogenital-cancer risk. […] One of the most surprising findings, was that smoking appears to play a significant role in anal-cancer development that is independent of other behavioral risk factors, such as sexual activity, she said.

• #60 Anal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Anal_cancer

  Anal cancer is typically a squamous cell carcinoma. […] Most anal cancers are squamous cell carcinomas (epidermoid carcinomas), that arises near the squamocolumnar junction. […] Based on the study in Denmark and Sweden, Parkin estimated that 90% of anal cancers are attributable to HPV. […] Epidemiologist Janet Daling, Ph.D., a member of Fred Hutchinson’s Public Health Sciences Division, and her team found that smoking appears to play a significant role in anal-cancer development that is independent of other behavioral risk factors, such as sexual activity. […] The mechanism behind smoking and anal-cancer development is unknown, but researchers speculate that smoking interferes with a process called apoptosis, or programmed cell death, which helps rid the body of abnormal cells that could turn cancerous.

• #61 Lifestyle links to anal cancer | Fred Hutchinson Cancer Center

  https://www.fredhutch.org/en/news/center-news/2004/07/anal-cancer.html

  „Current smoking is a very important promoter of the disease,” said Daling, also a professor of epidemiology at the University of Washington School of Public Health and Community Medicine. […] „Even in controlling for other risk factors, like the number of sexual partners, anal intercourse and HPV status, smoking was a strong risk factor for squamous-cell anal cancer,” Daling said, referring to the most common type of anal cancer. […] The mechanism behind smoking and anal-cancer development is unknown, but researchers speculate that smoking interferes with a process called apoptosis, or programmed cell death, which helps rid the body of abnormal cells that could turn cancerous. […] Other risk factors associated with increased anal-cancer risk included gay or bisexual orientation among men, a high number of lifetime sexual partners and a history of receptive anal sex.

• #62 Anal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Anal_cancer

  Anal cancer is typically a squamous cell carcinoma. […] Most anal cancers are squamous cell carcinomas (epidermoid carcinomas), that arises near the squamocolumnar junction. […] Based on the study in Denmark and Sweden, Parkin estimated that 90% of anal cancers are attributable to HPV. […] Epidemiologist Janet Daling, Ph.D., a member of Fred Hutchinson’s Public Health Sciences Division, and her team found that smoking appears to play a significant role in anal-cancer development that is independent of other behavioral risk factors, such as sexual activity. […] The mechanism behind smoking and anal-cancer development is unknown, but researchers speculate that smoking interferes with a process called apoptosis, or programmed cell death, which helps rid the body of abnormal cells that could turn cancerous.

• #63 Anal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Anal_cancer

  Another possibility is that smoking suppresses the immune system, which can decrease the body’s ability to clear persistent infection or abnormal cells. […] Current gold-standard therapy is the combination of chemotherapy and radiation treatment to reduce the necessity of debilitating surgery. […] This „combined modality” approach has led to the increased preservation of an intact anal sphincter, and therefore improved quality of life after definitive treatment.

• #64 Lifestyle links to anal cancer | Fred Hutchinson Cancer Center

  https://www.fredhutch.org/en/news/center-news/2004/07/anal-cancer.html

  „Current smoking is a very important promoter of the disease,” said Daling, also a professor of epidemiology at the University of Washington School of Public Health and Community Medicine. […] „Even in controlling for other risk factors, like the number of sexual partners, anal intercourse and HPV status, smoking was a strong risk factor for squamous-cell anal cancer,” Daling said, referring to the most common type of anal cancer. […] The mechanism behind smoking and anal-cancer development is unknown, but researchers speculate that smoking interferes with a process called apoptosis, or programmed cell death, which helps rid the body of abnormal cells that could turn cancerous. […] Other risk factors associated with increased anal-cancer risk included gay or bisexual orientation among men, a high number of lifetime sexual partners and a history of receptive anal sex.

• #65 Lifestyle links to anal cancer | Fred Hutchinson Cancer Center

  https://www.fredhutch.org/en/news/center-news/2004/07/anal-cancer.html

  „Current smoking is a very important promoter of the disease,” said Daling, also a professor of epidemiology at the University of Washington School of Public Health and Community Medicine. […] „Even in controlling for other risk factors, like the number of sexual partners, anal intercourse and HPV status, smoking was a strong risk factor for squamous-cell anal cancer,” Daling said, referring to the most common type of anal cancer. […] The mechanism behind smoking and anal-cancer development is unknown, but researchers speculate that smoking interferes with a process called apoptosis, or programmed cell death, which helps rid the body of abnormal cells that could turn cancerous. […] Other risk factors associated with increased anal-cancer risk included gay or bisexual orientation among men, a high number of lifetime sexual partners and a history of receptive anal sex.

• #66 Lifestyle links to anal cancer | Fred Hutchinson Cancer Center

  https://www.fredhutch.org/en/news/center-news/2004/07/anal-cancer.html

  „Current smoking is a very important promoter of the disease,” said Daling, also a professor of epidemiology at the University of Washington School of Public Health and Community Medicine. […] „Even in controlling for other risk factors, like the number of sexual partners, anal intercourse and HPV status, smoking was a strong risk factor for squamous-cell anal cancer,” Daling said, referring to the most common type of anal cancer. […] The mechanism behind smoking and anal-cancer development is unknown, but researchers speculate that smoking interferes with a process called apoptosis, or programmed cell death, which helps rid the body of abnormal cells that could turn cancerous. […] Other risk factors associated with increased anal-cancer risk included gay or bisexual orientation among men, a high number of lifetime sexual partners and a history of receptive anal sex.

• #67 Lifestyle links to anal cancer | Fred Hutchinson Cancer Center

  https://www.fredhutch.org/en/news/center-news/2004/07/anal-cancer.html

  „Current smoking is a very important promoter of the disease,” said Daling, also a professor of epidemiology at the University of Washington School of Public Health and Community Medicine. […] „Even in controlling for other risk factors, like the number of sexual partners, anal intercourse and HPV status, smoking was a strong risk factor for squamous-cell anal cancer,” Daling said, referring to the most common type of anal cancer. […] The mechanism behind smoking and anal-cancer development is unknown, but researchers speculate that smoking interferes with a process called apoptosis, or programmed cell death, which helps rid the body of abnormal cells that could turn cancerous. […] Other risk factors associated with increased anal-cancer risk included gay or bisexual orientation among men, a high number of lifetime sexual partners and a history of receptive anal sex.

• #68 Lifestyle links to anal cancer | Fred Hutchinson Cancer Center

  https://www.fredhutch.org/en/news/center-news/2004/07/anal-cancer.html

  „Current smoking is a very important promoter of the disease,” said Daling, also a professor of epidemiology at the University of Washington School of Public Health and Community Medicine. […] „Even in controlling for other risk factors, like the number of sexual partners, anal intercourse and HPV status, smoking was a strong risk factor for squamous-cell anal cancer,” Daling said, referring to the most common type of anal cancer. […] The mechanism behind smoking and anal-cancer development is unknown, but researchers speculate that smoking interferes with a process called apoptosis, or programmed cell death, which helps rid the body of abnormal cells that could turn cancerous. […] Other risk factors associated with increased anal-cancer risk included gay or bisexual orientation among men, a high number of lifetime sexual partners and a history of receptive anal sex.

• #69 Lifestyle links to anal cancer | Fred Hutchinson Cancer Center

  https://www.fredhutch.org/en/news/center-news/2004/07/anal-cancer.html

  The study also suggested that the overall increase in anal cancer rates might be partially attributable to an increase in the average number of lifetime sexual partners and an increase in the number of people engaging in anal sex, particularly among women. […] „However, I suspect that increased incidence of anal intercourse among both men and women is most likely to be the primary cause behind the rise in anal cancer.”

• #70 Prevalence of HPV in anal cancer: exploring the role of infection and inflammation | Infectious Agents and Cancer | Full Text

  https://infectagentscancer.biomedcentral.com/articles/10.1186/s13027-024-00624-0

  By integrating into the host DNA or remaining as extra-chromosomal epitopes, HPV causes normal squamous anal epithelium to undergo a neoplastic transformation that leads to low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and ultimately squamous cell carcinoma of the anus (SCCA). […] E6 and E7 are two oncoproteins encoded by the HPV genome, whose expression is crucial for the viruss ability to promote cellular proliferation and evade apoptosis in infected cells. […] The interplay between HPV and HIV coinfection complicates the pathogenesis of anal cancer, as HIV can enhance HPVs oncogenic potential by impairing immune responses and epithelial integrity. […] In anal cancer, the chronic inflammatory environment created by HPV and HIV infection facilitates the evasion of apoptosis and immune recognition, allowing tumor cells to proliferate and metastasize.

• #71 Anal carcinoma – exploring the epidemiology, risk factors, pathophysiology, diagnosis, and treatment

  https://www.wjgnet.com/2220-315x/full/v14/i3/98525.htm

  Anal carcinoma is a relatively rare tumor that accounts for approximately 2% of gastrointestinal malignancies and less than 7% of anorectal cancers. […] The pathogenesis of anal carcinoma is believed to be linked to human papillomavirus-related inflammation, leading to dysplasia and progression to cancer. […] Integration of HPV double-stranded DNA into the host cell genome facilitates the expression of viral oncoproteins E6 and E7, promoting tumor oncogenesis of anal SCC. […] HPV-related neoplasm requires E6 and E7 expressions to establish and maintain a transformed state. […] This complex interplay serves as the primary mechanism for HPV-related anal SCC. […] HIV-associated anal cancer is believed to be related to microsatellite instability, leading to the progression of invasive carcinoma.

• #72 SciELO Brazil – Anal squamous carcinoma: a new AIDS-defining cancer? Case report and literature review Anal squamous carcinoma: a new AIDS-defining cancer? Case report and literature review

  https://www.scielo.br/j/rimtsp/a/Y7MVRr8KXfHWgNVKpM4Ktkf/

  Squamous anal cell carcinoma is a rare malignancy that represents the 1.5% to 2% of all the lower digestive tract cancers. […] Human papillomavirus is strongly associated with the pathogenesis of anal cancer. […] The probability to develop anal cancer has been reported as two to 14 times higher in HIV-positive MSM in comparison with those who are HIV-negative. […] HPV play an important role in the pathogenesis of both CIN and AIN, and HPV DNA was found in many anal cancers biopsy smears. […] Although HAART reduce the incidence of opportunistic infections and AIDS-defining cancers, the incidence of SACC is increasing since the widespread use of antiretroviral therapy. […] A better prognosis is related with the early diagnosis and the treatment based on the combination of HAART plus chemoradiotherapy.

• #73 SciELO Brazil – Anal squamous carcinoma: a new AIDS-defining cancer? Case report and literature review Anal squamous carcinoma: a new AIDS-defining cancer? Case report and literature review

  https://www.scielo.br/j/rimtsp/a/Y7MVRr8KXfHWgNVKpM4Ktkf/

  Squamous anal cell carcinoma is a rare malignancy that represents the 1.5% to 2% of all the lower digestive tract cancers. […] Human papillomavirus is strongly associated with the pathogenesis of anal cancer. […] The probability to develop anal cancer has been reported as two to 14 times higher in HIV-positive MSM in comparison with those who are HIV-negative. […] HPV play an important role in the pathogenesis of both CIN and AIN, and HPV DNA was found in many anal cancers biopsy smears. […] Although HAART reduce the incidence of opportunistic infections and AIDS-defining cancers, the incidence of SACC is increasing since the widespread use of antiretroviral therapy. […] A better prognosis is related with the early diagnosis and the treatment based on the combination of HAART plus chemoradiotherapy.

• #74 The Role of Inflammation in Anal Cancer

  https://www.mdpi.com/2079-9721/10/2/27

  However, there are still many molecular and cellular mechanisms that remain largely unexplored. Further studies on this topic could be of tremendous significance in elucidating anal cancer pathogenesis and could lead to the development of new immunotherapeutic approaches and, eventually, better outcomes.

• #75 Anal squamous cell carcinoma: An evolution in disease and management

  https://www.wjgnet.com/1007-9327/full/v20/i36/13052.htm

  A clear distinction must be made between anal canal carcinoma and anal margin carcinoma, since the treatment can differ radically between the two. […] There is a very clear link between human papilloma virus (HPV) infection and anal cancer. HPV infects the skin and mucous membranes of the mouth, anus, penis and female reproductive tract. […] The histology of tissue lining the anal canal is varied. […] By far the most common malignancy of the anal canal and anal margin is squamous cell carcinoma. […] The role of cisplatin has also been evaluated in multicenter, prospective randomized controlled trials. […] The recently reported multicenter ACT II trial from the UK also demonstrated no difference in response rates or in survival between patients receiving mitomycin C vs cisplatin. […] Current NCCN guidelines recommend 5-FU with mitomycin C and concurrent radiotherapy for all localized anal canal carcinomas. […] Anal Pap smear and high-resolution anoscopy are emerging as useful screening tools to identify precancerous lesions. Vaccination against HPV has been shown to prevent progression of precancerous lesions in high-risk individuals.

• #76 Anal Cancer: Practice Essentials, Pathophysiology, Epidemiology

  https://emedicine.medscape.com/article/2500052-overview

  Anal squamous cell cancer is believed to be directly linked to the presence of a complex inflammatory process most commonly caused by HPV infection (particularly with serotypes 16 and 18) in the histologically unique area of the anal squamocolumnar epithelium. In one Scandinavian study, serotype 16 HPV DNA was detected in 73% of anal cancer specimens, and serotype 16, 18, or both was detected in 84% of specimens. In contrast, no rectal cancer specimens contained HPV DNA. […] Active HPV infection affects approximately 10% of women worldwide. The high-risk HPV serotypes 16 and 18, which are responsible for most high-grade intraepithelial lesions that may progress to cancer, along with the low-risk serotypes 6 and 11, were targeted in the widely available quadrivalent HPV vaccine (the current nonavalent HPV vaccine covers serotypes 6, 11, 16, 18, 31, 33, 45, 52, and 58).

• #77 Anal cancer incidence rises in white, Hispanic older women: study – McKnight’s Long-Term Care News

  https://www.mcknights.com/news/anal-cancer-incidence-rises-in-white-hispanic-older-women-study/

  The rates of anal cancer have risen steadily in the United States, and the biggest increases were in older women especially white and Hispanic ones, according to a new report. […] While the exact reasons behind this trend remain unclear, most older women were beyond the recommended age for human papillomavirus vaccination when it first became widely available, Robinson noted. […] Human papillomavirus (HPV) is the virus responsible for 90% of anal cancers. […] More than 90% of cases are linked to chronic HPV infection. Typically, screening for anal HPV, dysplasia and cancer is recommended for high-risk groups that is, people with HIV, bone marrow transplant recipients and other immunocompromised individuals but older women, to this point, have not been included in that group.

• #78 Anal squamous cell carcinoma: An evolution in disease and management

  https://www.wjgnet.com/1007-9327/full/v20/i36/13052.htm

  A clear distinction must be made between anal canal carcinoma and anal margin carcinoma, since the treatment can differ radically between the two. […] There is a very clear link between human papilloma virus (HPV) infection and anal cancer. HPV infects the skin and mucous membranes of the mouth, anus, penis and female reproductive tract. […] The histology of tissue lining the anal canal is varied. […] By far the most common malignancy of the anal canal and anal margin is squamous cell carcinoma. […] The role of cisplatin has also been evaluated in multicenter, prospective randomized controlled trials. […] The recently reported multicenter ACT II trial from the UK also demonstrated no difference in response rates or in survival between patients receiving mitomycin C vs cisplatin. […] Current NCCN guidelines recommend 5-FU with mitomycin C and concurrent radiotherapy for all localized anal canal carcinomas. […] Anal Pap smear and high-resolution anoscopy are emerging as useful screening tools to identify precancerous lesions. Vaccination against HPV has been shown to prevent progression of precancerous lesions in high-risk individuals.

• #79 Anal squamous cell carcinoma: An evolution in disease and management

  https://www.wjgnet.com/1007-9327/full/v20/i36/13052.htm

  A clear distinction must be made between anal canal carcinoma and anal margin carcinoma, since the treatment can differ radically between the two. […] There is a very clear link between human papilloma virus (HPV) infection and anal cancer. HPV infects the skin and mucous membranes of the mouth, anus, penis and female reproductive tract. […] The histology of tissue lining the anal canal is varied. […] By far the most common malignancy of the anal canal and anal margin is squamous cell carcinoma. […] The role of cisplatin has also been evaluated in multicenter, prospective randomized controlled trials. […] The recently reported multicenter ACT II trial from the UK also demonstrated no difference in response rates or in survival between patients receiving mitomycin C vs cisplatin. […] Current NCCN guidelines recommend 5-FU with mitomycin C and concurrent radiotherapy for all localized anal canal carcinomas. […] Anal Pap smear and high-resolution anoscopy are emerging as useful screening tools to identify precancerous lesions. Vaccination against HPV has been shown to prevent progression of precancerous lesions in high-risk individuals.

• #80 Anal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Anal_cancer

  Another possibility is that smoking suppresses the immune system, which can decrease the body’s ability to clear persistent infection or abnormal cells. […] Current gold-standard therapy is the combination of chemotherapy and radiation treatment to reduce the necessity of debilitating surgery. […] This „combined modality” approach has led to the increased preservation of an intact anal sphincter, and therefore improved quality of life after definitive treatment.

• #81 Anal cancer – Wikipedia

  https://en.wikipedia.org/wiki/Anal_cancer

  Another possibility is that smoking suppresses the immune system, which can decrease the body’s ability to clear persistent infection or abnormal cells. […] Current gold-standard therapy is the combination of chemotherapy and radiation treatment to reduce the necessity of debilitating surgery. […] This „combined modality” approach has led to the increased preservation of an intact anal sphincter, and therefore improved quality of life after definitive treatment.

• #82 British Journal of Cancer Research

  https://britishjournalofcancerresearch.com/treatment-of-anal-carcinoma-a-review-of-the-literature

  Intensity-modulated radiation therapy (IMRT) allows for beam shaping and has proven to be particularly useful in irregular pelvic treatment volumes, such as those of anal carcinomas. […] The use of IMRT also proved to reduce toxicity-related interruptions, which may be responsible to some extent for the increased local control associated with the use of this technique. […] There is a paucity of data on the ideal treatment for patients with M1 anal carcinoma, with few phase III trials conducted to date. […] From the 70s until the 90s, important advancements were made in the realm of treatment for anal carcinoma, which constitutes a mostly curable illness nowadays.

• #83 British Journal of Cancer Research

  https://britishjournalofcancerresearch.com/treatment-of-anal-carcinoma-a-review-of-the-literature

  Intensity-modulated radiation therapy (IMRT) allows for beam shaping and has proven to be particularly useful in irregular pelvic treatment volumes, such as those of anal carcinomas. […] The use of IMRT also proved to reduce toxicity-related interruptions, which may be responsible to some extent for the increased local control associated with the use of this technique. […] There is a paucity of data on the ideal treatment for patients with M1 anal carcinoma, with few phase III trials conducted to date. […] From the 70s until the 90s, important advancements were made in the realm of treatment for anal carcinoma, which constitutes a mostly curable illness nowadays.

• #84 Prevalence of HPV in anal cancer: exploring the role of infection and inflammation | Infectious Agents and Cancer | Full Text

  https://infectagentscancer.biomedcentral.com/articles/10.1186/s13027-024-00624-0

  Several pro-inflammatory pathways are involved in this process, notably the NF-B signaling pathway. […] The PD-1/PD-L1 pathway appears to play a central role in suppressing anti-tumor immunity. […] A deeper understanding of how HIV, HPV, and inflammation coordinately disrupt CD8+T cell responses and promote oncogene expression could reveal new therapeutic targets. […] Immunotherapies blocking the PD-1/PD-L1 axis show promise, but further research is needed on optimizing these approaches based on each patients viral, inflammatory and immune status.

• #85 Recent advances in the management of anal cancer.

  https://vivo.weill.cornell.edu/display/pubid30345012

  Anal cancer is a rare condition, although its incidence has been increasing over the past several decades, particularly in women. The majority of anal cancers are squamous cell cancers and are linked with human papilloma virus (HPV) infection. Recent work in HPV basic science has delineated the mechanism by which the virus leads to the development of anal cancer. […] Exciting developments in immune therapies targeting HPV oncoproteins as well as therapeutic vaccines may soon dramatically change the way patients with anal cancer are managed.

• #86 HPV infection, anal intra-epithelial neoplasia (AIN) and anal cancer: current issues | BMC Cancer | Full Text

  https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-12-398

  Progression of AIN to anal SCC has been assessed in small studies with surveillance and treatment, but with a relatively short follow up of 510years. […] The authors suggest that immunosuppressed patients (6 in this study all from long term oral therapy, such as corticosteroids, for various conditions) and those with multifocal AIN (7 in this study) are at higher risk of malignant transformation. […] However, a recent meta-analysis has indicated that progression rates from HGAIN to anal cancer are approximately one in 600 per year in HIV-positive MSM and one in 4000 per year in HIV-negative MSM patients, substantially lower than the one in 80 per year observed in comparable cervical disease. […] There are strong supportive data for the contention that HGAIN is a precursor lesion to invasive anal carcinoma. […] There is now a need for multi-centre prospective studies on progression of AIN 3 to cancer and on the effectiveness of treatment to reduce the incidence of anal cancer.

• #87 Management of Anal Cancer in 2010 Part 2: Current Treatment Standards and Future Directions

  https://www.cancernetwork.com/view/management-anal-cancer-2010-part-2-current-treatment-standards-and-future-directions

  The treatment of HIV-positive patients in the HAART era is feasible and can result in long-term cures. […] Improvements in systemic treatments are also being investigated. […] More efforts should be made to investigate the relevance of HPV-positivity in anal cancer in relationship to prognosis and treatment outcome. […] It has long been shown that a combination of a taxane, 5-FU, and cisplatin when followed by radiation therapy results in superior overall survival in head and neck cancers, compared to fluorouracil plus cisplatin and radiation.

• #88 Pathology of Anal Cancer – PubMed

  https://pubmed.ncbi.nlm.nih.gov/27889037/

  Anal canal cancer is rather an uncommon disease but its incidence is increasing. […] HPV infection has a key role in precancerous lesions and cancer development by the production of E6 and E7 oncoproteins. […] Currently, there are no biomarkers able to predict prognosis or response to treatment in clinical practice.

• #89 Prevalence of HPV in anal cancer: exploring the role of infection and inflammation | Infectious Agents and Cancer | Full Text

  https://infectagentscancer.biomedcentral.com/articles/10.1186/s13027-024-00624-0

  Several pro-inflammatory pathways are involved in this process, notably the NF-B signaling pathway. […] The PD-1/PD-L1 pathway appears to play a central role in suppressing anti-tumor immunity. […] A deeper understanding of how HIV, HPV, and inflammation coordinately disrupt CD8+T cell responses and promote oncogene expression could reveal new therapeutic targets. […] Immunotherapies blocking the PD-1/PD-L1 axis show promise, but further research is needed on optimizing these approaches based on each patients viral, inflammatory and immune status.

• #90 The Role of Inflammation in Anal Cancer

  https://www.mdpi.com/2079-9721/10/2/27

  However, there are still many molecular and cellular mechanisms that remain largely unexplored. Further studies on this topic could be of tremendous significance in elucidating anal cancer pathogenesis and could lead to the development of new immunotherapeutic approaches and, eventually, better outcomes.

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