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Abstract Background Cervical cancer is preventable through screening and vaccination against high-risk human papillomavirus (hr-HPV). For a screening program to be successful it is vital that the clinical management and follow-up regime of patients with abnormal screening results is well developed and that the attendance rate for follow-up is high. The aim of the study was to analyze how effective conization with recommended follow-up was in preventing subsequent cervical cancer, and to evaluate how clinical follow-up recommendations are obeyed in the region of Skåne, Sweden. Methods All women (n = 8835) who had undergone conization in the region of Skåne, Sweden, between the years of 2015 and 2021 were identified. Individuals with confirmed cervical cancer in the conization material were referred for additional treatment (n = 114), leaving 8721 included in the follow-up. Adherence to follow-up and cytological, histopathological and HPV status at follow-up were collected at eight, 12 and 24 months post-conization. The total follow-up time was from January 1, 2015, to January 30, 2023. Results Within 12 months post-conization, 90% of the patients conducted a cytological cervical sample. The rates of a negative test of cure (HPV negative and normal cytology) were 69.7%, 76.3% and 84.4% at eight, 12 and 24 months post-conization respectively. The clearance of HPV was 79.6%, 80.8% and 87.8% at eight, 12 and 24 months post-conization respectively. Out of 5613 patients with a negative test of cure within one year after conization, no cervical cancer was found during follow-up and 11 (0.2%) women developed high-grade intraepithelial lesions/adenocarcinoma in situ (HSIL/AIS) with an average time from conization to new diagnosis of 42 months. The mean follow-up time was 32.1 months. Conclusions The clearance rate of hr-HPV post cervical conization due to dysplasia appears to be high within eight months. With a negative test of cure post cervical conization, the risk of cervical cancer within the following three years seems to be extremely low and the risk of developing HSIL/AIS was lower than the incidence of HSIL/AIS in the general screening population.

Women treated for CIN2/3 remain at increased risk of recurrent CIN and cervical cancer, and therefore posttreatment surveillance is recommended. This post hoc analysis evaluates the potential of methylation markers ASCL1/LHX8 and FAM19A4/miR124‐2 for posttreatment detection of recurrent CIN2/3. Cervical scrapes taken at 6 and 12 months posttreatment of 364 women treated for CIN2/3 were tested for methylation of ASCL1/LHX8 and FAM19A4/miR124‐2 using quantitative multiplex methylation‐specific PCR. Performance of the methylation tests were calculated and compared with the performance of HPV and/or cytology. Methylation levels of recurrent CIN were compared between women with a persistent HPV infection, and women with an incident HPV infection or without HPV infection. Recurrent CIN2/3 was detected in 42 women (11.5%), including 28 women with CIN2 and 14 with CIN3. ASCL1/LHX8 tested positive in 13/14 (92.9%) of recurrent CIN3 and 13/27 (48.1%) of recurrent CIN2. FAM19A4/miR124‐2 tested positive in 14/14 (100%) of recurrent CIN3 and 10/27 (37.0%) of recurrent CIN2. Combined HPV and/or methylation testing showed similar positivity rates as HPV and/or cytology. The CIN2/3 risk at 12 months posttreatment was 30.8% after a positive ASCL1/LHX8 result at 6 months posttreatment. Methylation levels of CIN2/3 in women with a persistent HPV infection were significantly higher compared with women with an incident or no HPV infection. In conclusion, posttreatment monitoring by methylation analysis of ASCL1/LHX8 and FAM19A4/miR124‐2 showed a good performance for the detection of recurrent CIN. DNA methylation testing can help to identify women with recurrent CIN that require re‐treatment. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is preventable through screening and vaccination against high-risk human papillomavirus (hr-HPV). For a screening program to be successful it is vital that the clinical management and follow-up regime of patients with abnormal screening results is well developed and that the attendance rate for follow-up is high. The aim of the study was to analyze how effective conization with recommended follow-up was in preventing subsequent cervical cancer, and to evaluate how clinical follow-up recommendations are obeyed in the region of Skåne, Sweden. Methods: All women (n = 8835) who had undergone conization in the region of Skåne, Sweden, between the years of 2015 and 2021 were identified. Individuals with confirmed cervical cancer in the conization material were referred for additional treatment (n = 114), leaving 8721 included in the follow-up. Adherence to follow-up and cytological, histopathological and HPV status at follow-up were collected at eight, 12 and 24 months post-conization. The total follow-up time was from January 1, 2015, to January 30, 2023. Results: Within 12 months post-conization, 90% of the patients conducted a cytological cervical sample. The rates of a negative test of cure (HPV negative and normal cytology) were 69.7%, 76.3% and 84.4% at eight, 12 and 24 months post-conization respectively. The clearance of HPV was 79.6%, 80.8% and 87.8% at eight, 12 and 24 months post-conization respectively. Out of 5613 patients with a negative test of cure within one year after conization, no cervical cancer was found during follow-up and 11 (0.2%) women developed high-grade intraepithelial lesions/adenocarcinoma in situ (HSIL/AIS) with an average time from conization to new diagnosis of 42 months. The mean follow-up time was 32.1 months. Conclusions: The clearance rate of hr-HPV post cervical conization due to dysplasia appears to be high within eight months. With a negative test of cure post cervical conization, the risk of cervical cancer within the following three years seems to be extremely low and the risk of developing HSIL/AIS was lower than the incidence of HSIL/AIS in the general screening population. [ABSTRACT FROM AUTHOR]

Abstract Background The optimal posttreatment surveillance strategy for nasopharyngeal carcinoma (NPC) remains unclear. Circulating cell-free Epstein-Barr virus (cfEBV) DNA has been recognized as a promising biomarker to facilitate early detection of NPC recurrence. Therefore, we aim to determine whether integrating circulating cfEBV DNA into NPC follow-up is cost-effective. Methods For each stage of asymptomatic nonmetastatic NPC patients after complete remission to primary NPC treatment, we developed a Markov model to compare the cost-effectiveness of the following surveillance strategies: routine follow-up strategy, i.e., (1) routine clinical physical examination; routine imaging strategies, including (2) routine magnetic resonance imaging plus computed tomography plus bone scintigraphy (MRI + CT + BS); and (3) routine 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT); cfEBV DNA-guided imaging strategies, including (4) cfEBV DNA-guided MRI + CT + BS and (5) cfEBV DNA-guided PET/CT. Clinical probabilities, utilities, and costs were derived from published studies or databases. Sensitivity analyses were performed. Results For all disease stages, cfEBV DNA-guided imaging strategies demonstrated similar survival benefits but were considerably more economical than routine imaging strategies. They only required approximately one quarter of the number of imaging studies compared with routine imaging strategies to detect one recurrence. Specifically, cfEBV DNA-guided MRI + CT + BS was most cost-effective for stage II (incremental cost-effectiveness ratio [ICER] $57,308/quality-adjusted life-year [QALY]) and stage III ($46,860/QALY) patients, while cfEBV DNA-guided PET/CT was most cost-effective for stage IV patients ($62,269/QALY). However, routine follow-up was adequate for stage I patients due to their low recurrence risk. Conclusions The cfEBV DNA-guided imaging strategies are effective and cost-effective follow-up methods in NPC. These liquid biopsy-based strategies offer evidence-based, stage-specific surveillance modalities for clinicians and reduce disease burden for patients.

Background: The optimal posttreatment surveillance strategy for nasopharyngeal carcinoma (NPC) remains unclear. Circulating cell-free Epstein-Barr virus (cfEBV) DNA has been recognized as a promising biomarker to facilitate early detection of NPC recurrence. Therefore, we aim to determine whether integrating circulating cfEBV DNA into NPC follow-up is cost-effective.Methods: For each stage of asymptomatic nonmetastatic NPC patients after complete remission to primary NPC treatment, we developed a Markov model to compare the cost-effectiveness of the following surveillance strategies: routine follow-up strategy, i.e., (1) routine clinical physical examination; routine imaging strategies, including (2) routine magnetic resonance imaging plus computed tomography plus bone scintigraphy (MRI + CT + BS); and (3) routine 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT); cfEBV DNA-guided imaging strategies, including (4) cfEBV DNA-guided MRI + CT + BS and (5) cfEBV DNA-guided PET/CT. Clinical probabilities, utilities, and costs were derived from published studies or databases. Sensitivity analyses were performed.Results: For all disease stages, cfEBV DNA-guided imaging strategies demonstrated similar survival benefits but were considerably more economical than routine imaging strategies. They only required approximately one quarter of the number of imaging studies compared with routine imaging strategies to detect one recurrence. Specifically, cfEBV DNA-guided MRI + CT + BS was most cost-effective for stage II (incremental cost-effectiveness ratio [ICER] $57,308/quality-adjusted life-year [QALY]) and stage III ($46,860/QALY) patients, while cfEBV DNA-guided PET/CT was most cost-effective for stage IV patients ($62,269/QALY). However, routine follow-up was adequate for stage I patients due to their low recurrence risk.Conclusions: The cfEBV DNA-guided imaging strategies are effective and cost-effective follow-up methods in NPC. These liquid biopsy-based strategies offer evidence-based, stage-specific surveillance modalities for clinicians and reduce disease burden for patients. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the performance of 18F‐fluorodeoxy‐d‐glucose positron emission tomography‐computed tomography (18F‐FDG PET/CT) in identifying local failure and regional failure following curative radiotherapy or surgery for head and neck squamous cell carcinoma. Methods: A comprehensive literature search identified studies published between January 2010 and August 2016. Diagnostic performance of 18F‐FDG PET/CT was evaluated for local failure/regional failure stratified by treatment‐to‐scan time interval of ≤3 versus >3 months. Results: Twenty‐four studies (2627 patients) were included. Compared to ≤3 months, 18F‐FDG PET/CT performed >3 months showed significantly improved sensitivity (87% vs 60%, P = 0.020) and specificity (93% vs 84%, P < 0.001) for local failure. There was no significant difference in sensitivity (79% vs 56%, P = 0.100) or specificity (95% vs 97%, P = 0.35) for regional failure >3 versus ≤3 months. Conclusions: This meta‐analysis confirms high specificity but modest sensitivity of posttreatment 18F‐FDG PET/CT for local failure and regional failure. Sensitivity and specificity are significantly improved when 18F‐FDG PET/CT is performed >3 months for local failure. [ABSTRACT FROM AUTHOR]

The oral cavity is the commonest subsite of head and neck squamous cell carcinoma (HNSCC). Because of the rising incidence and increasing survival, more patients will be enrolled in a routine follow-up program. This review gives an overview of the evidence and guideline recommendations concerning follow-up after oral squamous cell carcinoma (OSCC). There is limited evidence concerning the effectiveness of follow-up after OSCC. This lack of evidence is reflected in a variation in guideline recommendations with respect to test interval and duration (i.e. for 3-5 years or lifelong). Most studies on the value of routine follow-up after curative treatment include all HNSCC subsites. The available literature shows, that these subsites have a different timing of recurrence and a different risk of second primary tumors at different locations. This leaves no rationale for applying the same follow-up program to each of the HNSCC subsites. There is agreement in the literature that OSCC follow-up can either be discontinued after two or three years or should be lifelong based on the risk of second primary tumors. Many authors advocate a personalized follow-up regimen that is based on the risk of new disease rather than a one-size-fits-all surveillance program. The literature is conflicting about the survival benefits of asymptomatic detection of new disease for HNSCC. To aid the development of evidence-based follow-up advise after OSCC, future research should focus on risk stratification, the value of symptom-free detection of recurrences and the active role that patients might play in determining their own follow-up regimen. [ABSTRACT FROM AUTHOR]

There has been a steady decline in breast cancer mortality that has led to a significant increase in the number of patients surviving breast cancer. We will review in this manuscript the evidence and guidelines for posttreatment surveillance of patients with breast cancer as well as the management options for patients who are diagnosed with local-regional and distant recurrences. [ABSTRACT FROM AUTHOR]

Objective: We conducted a pooled analysis of published studies to compare the performance of human papillomavirus (HPV) testing and cytology in detecting residual or recurrent diseases after treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3). Methods: Source articles presenting data on posttreatment HPV testing were identified from the National Library of Medicine (PubMed) database. We included 5,319 cases from 33 articles published between 1996 and 2013. Results: The pooled sensitivity of high-risk HPV testing (0.92; 95% confidence interval [CI], 0.90 to 0.94) for detecting posttreatment CIN 2 or worse (CIN 2+) was much higher than that of cytology (0.76; 95% CI, 0.71 to 0.80). Co-testing of HPV testing and cytology maximized the sensitivity (0.93; 95% CI, 0.87 to 0.96), while HPV genotyping (detection of the same genotype between pre- and posttreatments) did not improve the sensitivity (0.89; 95% CI, 0.82 to 0.94) compared with high-risk HPV testing alone. The specificity of high-risk HPV testing (0.83; 95% CI, 0.82 to 0.84) was similar to that of cytology (0.85; 95% CI, 0.84 to 0.87) and HPV genotyping (0.83; 95% CI, 0.81 to 0.85), while co-testing had reduced specificity (0.76; 95% CI, 0.75 to 0.78). For women with positive surgical margins, high-risk HPV testing provided remarkable risk discrimination between test-positives and test-negatives (absolute risk of residual CIN 2+ 74.4% [95% CI, 64.0 to 82.6] vs. 0.8% [95% CI, 0.15 to 4.6]; p<0.001). Conclusion: Our findings recommend the addition of high-risk HPV testing, either alone or in conjunction with cytology, to posttreatment surveillance strategies. HPV testing can identify populations at greatest risk of posttreatment CIN 2+ lesions, especially among women with positive section margins. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the performance of 18 F-fluorodeoxy-d-glucose positron emission tomography-computed tomography ( 18 F-FDG PET/CT) in identifying local failure and regional failure following curative radiotherapy or surgery for head and neck squamous cell carcinoma., Methods: A comprehensive literature search identified studies published between January 2010 and August 2016. Diagnostic performance of 18 F-FDG PET/CT was evaluated for local failure/regional failure stratified by treatment-to-scan time interval of ≤3 versus >3 months., Results: Twenty-four studies (2627 patients) were included. Compared to ≤3 months, 18 F-FDG PET/CT performed >3 months showed significantly improved sensitivity (87% vs 60%, P = 0.020) and specificity (93% vs 84%, P < 0.001) for local failure. There was no significant difference in sensitivity (79% vs 56%, P = 0.100) or specificity (95% vs 97%, P = 0.35) for regional failure >3 versus ≤3 months., Conclusions: This meta-analysis confirms high specificity but modest sensitivity of posttreatment 18 F-FDG PET/CT for local failure and regional failure. Sensitivity and specificity are significantly improved when 18 F-FDG PET/CT is performed >3 months for local failure., (© 2018 Wiley Periodicals, Inc.)

The oral cavity is the commonest subsite of head and neck squamous cell carcinoma (HNSCC). Because of the rising incidence and increasing survival, more patients will be enrolled in a routine follow-up program. This review gives an overview of the evidence and guideline recommendations concerning follow-up after oral squamous cell carcinoma (OSCC). There is limited evidence concerning the effectiveness of follow-up after OSCC. This lack of evidence is reflected in a variation in guideline recommendations with respect to test interval and duration (i.e. for 3-5 years or lifelong). Most studies on the value of routine follow-up after curative treatment include all HNSCC subsites. The available literature shows, that these subsites have a different timing of recurrence and a different risk of second primary tumors at different locations. This leaves no rationale for applying the same follow-up program to each of the HNSCC subsites. There is agreement in the literature that OSCC follow-up can either be discontinued after two or three years or should be lifelong based on the risk of second primary tumors. Many authors advocate a personalized follow-up regimen that is based on the risk of new disease rather than a one-size-fits-all surveillance program. The literature is conflicting about the survival benefits of asymptomatic detection of new disease for HNSCC. To aid the development of evidence-based follow-up advise after OSCC, future research should focus on risk stratification, the value of symptom-free detection of recurrences and the active role that patients might play in determining their own follow-up regimen., (Copyright © 2018. Published by Elsevier Ltd.)

The prognosis of head and neck squamous cell carcinoma (HNSCC) is largely based on disease stage. Despite improvements in treatment, recurrence rates are still considered high. Currently, disease progression or regression after curative treatment is monitored by clinical evaluation combined with flexible endoscopy and/or imaging. However, specificity of imaging is low due to the posttreatment effects. Detection of circulating tumor DNA (ctDNA) from blood samples of HNSCC patients is a minimally invasive technique that could lead to an earlier detection of recurrence. In addition, digital droplet PCR (ddPCR) could be used to sensitively detect these mutational targets. Future study on ctDNA using ddPCR in blood samples of HNSCC patients is recommended during the follow-up stage to detect recurrences in a timely manner., (© 2016 S. Karger AG, Basel.)

Objective: We conducted a pooled analysis of published studies to compare the performance of human papillomavirus (HPV) testing and cytology in detecting residual or recurrent diseases after treatment for cervical intraepithelial neoplasia grade 2 or 3 (CIN 2/3)., Methods: Source articles presenting data on posttreatment HPV testing were identified from the National Library of Medicine (PubMed) database. We included 5,319 cases from 33 articles published between 1996 and 2013., Results: The pooled sensitivity of high-risk HPV testing (0.92; 95% confidence interval [CI], 0.90 to 0.94) for detecting posttreatment CIN 2 or worse (CIN 2+) was much higher than that of cytology (0.76; 95% CI, 0.71 to 0.80). Co-testing of HPV testing and cytology maximized the sensitivity (0.93; 95% CI, 0.87 to 0.96), while HPV genotyping (detection of the same genotype between pre- and posttreatments) did not improve the sensitivity (0.89; 95% CI, 0.82 to 0.94) compared with high-risk HPV testing alone. The specificity of high-risk HPV testing (0.83; 95% CI, 0.82 to 0.84) was similar to that of cytology (0.85; 95% CI, 0.84 to 0.87) and HPV genotyping (0.83; 95% CI, 0.81 to 0.85), while co-testing had reduced specificity (0.76; 95% CI, 0.75 to 0.78). For women with positive surgical margins, high-risk HPV testing provided remarkable risk discrimination between test-positives and test-negatives (absolute risk of residual CIN 2+ 74.4% [95% CI, 64.0 to 82.6] vs. 0.8% [95% CI, 0.15 to 4.6]; p<0.001)., Conclusion: Our findings recommend the addition of high-risk HPV testing, either alone or in conjunction with cytology, to posttreatment surveillance strategies. HPV testing can identify populations at greatest risk of posttreatment CIN 2+ lesions, especially among women with positive section margins.

Background: An estimated 750,000 melanoma survivors in the United States are at increased risk of subsequent primary cancers. Objective: We sought to assess the risk of developing subsequent primary cancers among people with cutaneous melanoma. Methods: Using 1992 to 2006 data from the National Cancer Institute Surveillance, Epidemiology, and End Results Program, 40,881 people with in situ melanoma and 76,041 people with invasive melanoma were followed up (mean of 5.6 years) for the development of subsequent primary cancers. The observed number of subsequent cancers was compared with those expected based on age-/race-/year-/site-specific rates in the Surveillance, Epidemiology, and End Results population. Standardized incidence ratios (SIRs) (SIR = observed number/expected number) were considered statistically significant if they differed from 1, with an alpha level of 0.05. Results: After a first primary in situ melanoma, risk was significantly elevated for subsequent invasive melanoma and chronic lymphocytic leukemia among men (SIRs = 8.43 and 1.44, respectively) and women (SIRs = 12.33 and 1.79, respectively). After a first primary invasive melanoma, risk was significantly elevated for subsequent invasive melanoma, thyroid cancer, non-Hodgkin lymphoma, and chronic lymphocytic leukemia among both men (SIRs = 12.50, 2.67, 1.56, and 1.57, respectively) and women (SIRs = 15.67, 1.77, 1.42, and 1.63, respectively). Limitations: Case ascertainment issues particularly affecting in situ melanoma cases could affect results. The role of detection bias in the diagnoses of some subsequent cancers cannot be completely eliminated. Conclusions: The findings of the study should guide the development of strategies such as posttreatment surveillance, screening, and ultraviolet exposure education among melanoma survivors to improve cancer survivorship. [Copyright &y& Elsevier]