Prognostic Significance of HPV DNA and p16 &lt;sup&gt;INK4a&lt;/sup&gt; in Anal Cancer: A Systematic Review and Meta-Analysis

Urbutė, Aivara; Rasmussen, Christina Louise; Belmonte, F.; Obermueller, Theresa; Prigge, Elena-Sophie; Arbyn, Marc; Verdoodt, Freija; Kjær, Susanne K.

doi:10.2139/ssrn.3417887

Cited by 4 publications

(9 citation statements)

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“…Overexpression of the E7 protein in the transforming phase of the HPV infection increases the expression of p16 by altering its epigenetic regulation [ 17 ]. Hence, p16 is widely used as a surrogate marker for HPV infection [ 17 , 18 ]. In our patient cohort, p16 expression was present in 42 samples (77.8%) and absent in 11 samples (20.4%).…”

Section: Resultsmentioning

confidence: 99%

Evaluation of PD-L1 Expression and HPV Genotyping in Anal Squamous Cell Carcinoma

Wessely

Heppt

Kammerbauer

et al. 2020

Cancers

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Anal squamous cell carcinoma (SCC) is a rare cancer with increasing incidence. Infection with high-risk human papillomavirus (HPV) subtypes is the major cause for its development. We retrospectively analyzed tumor samples from 54 anal SCC patients for infection with a panel of 32 HPV subtypes in a PCR-based approach, determined the PD-L1 expression status, and correlated the findings with the clinical data and the survival of the patients. Forty-two patients (77.8%) were HPV-positive and harbored at least one carcinogenic HPV subtype. HPV16 was the most frequently detected (n = 39, 72.2%). Four patients were infected with multiple HPV subtypes. HPV infection was significantly more often detected in female than in male patients (90.3% vs. 60.9%, p = 0.018). Patients with PD-L1 positive tumors showed a significantly better median overall survival (OS) compared with patients with PD-L1 negative tumors (69.3 vs. 28.3 months, p = 0.006). The median OS was significantly different among the distinct tumor stages (p = 0.029). Sex, grade of differentiation, and HPV infection status did not influence the median OS. Furthermore, HPV infection status and PD-L1 expression were not correlated. A multivariate Cox regression analysis revealed that PD-L1 expression status was an independent prognostic marker for survival (p = 0.012).

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Section: Resultsmentioning

confidence: 99%

Evaluation of PD-L1 Expression and HPV Genotyping in Anal Squamous Cell Carcinoma

Wessely

Heppt

Kammerbauer

et al. 2020

Cancers

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“…This might be due to the fact that according to Austrian regulations, HIV testing requires a special informed consent form. Only 54% of the centers indicated routine HPV testing of biopsies, although evidence for HPV positivity as a positive predictive marker for outcome is growing [7,8]. This might be because only one center indicated altering the treatment concept based on HPV status or because current guidelines [1,2] do not recommend routine HPV testing nor guidance of treatment decisions by HPV status to date.…”

Section: Work-upmentioning

confidence: 99%

Practice of radiation therapy for anal cancer in Austria—a survey on behalf of the Austrian radiation oncology society gastrointestinal tumor group (ÖGRO-GIT)

et al. 2021

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Purpose We conducted a patterns-of-care survey on chemoradiation for locoregionally confined anal cancer in Austria to evaluate areas of disagreement and to identify possible targets for further standardization. Methods An anonymous questionnaire comprising 38 questions was sent to all Austrian radiation oncology departments. Results were analyzed descriptively and compared to two international guidelines. Results The response rate was 93%. Work-up generally includes DRE, endoscopy, and cross-sectional imaging of chest/abdomen and pelvis. PET-CT is used by 38%. Screening for HIV and biopsies of suspicious lymph nodes are infrequently used. All centers perform IMRT, mainly with daily IGRT. Median doses to the primary are 54.7 Gy (T1–2) and 59.4 Gy (T3–4). Suspicious nodes receive a boost (median dose 54 Gy), while elective nodal areas are mainly treated with 45–50.4 Gy. Target delineation of elective nodal areas seems generally uniform, although disagreement exists regarding inclusion of the common iliac nodes. No agreement was found for OAR-delineation and dose constraints. Concurrent chemotherapy is mitomycin and 5‑FU/capecitabine. Supportive care beyond skin care is infrequently offered. Intensive follow-up is performed for at least 5 years. Treatment of T1N0 shows considerable disagreement. Conclusion We found a high rate of agreement between the centers and concordance with major guidelines. PET-CT, routine HIV testing, and biopsies of suspicious LN seem underrepresented. The largest controversy regarding target volumes concerns inclusion of the common iliac nodes. Prescribed doses are generally in line with the recommendations or higher. OAR delineation, dose constraints, supportive care, and treatment of early anal cancer represent areas for further standardization.

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“…The findings of this review, with an improved survival for women with HPV‐positive vaginal cancer, are in line with results found in similar studies investigating survival after other HPV‐related cancers. Within penile, vulvar, anal, and oropharyngeal cancer, HPV is relatively well‐established as a prognostic marker, 11–13,19 with HPV positivity signifying improved prognosis. Our findings are also in agreement with a previous review by Gadducci et al 40 They included three studies 30,35,41 (of which one 41 was excluded from our review because no formal survival analysis was conducted) and concluded that HPV positivity is associated with improved survival.…”

Section: Discussionmentioning

confidence: 99%

“…HPV is well‐established as a prognostic marker in several HPV‐related cancers such as vulvar, anal, and oropharyngeal cancer, 11–13 with HPV positivity being a predictor of improved prognosis. However, the evidence within the field of vaginal cancer remains sparse.…”

Section: Introductionmentioning

confidence: 99%

“…Overexpression of p16 protein is well‐established as a surrogate marker for the presence of a transforming high‐risk HPV infection in several types of HPV‐related cancer 15,16 . Furthermore, studies within vulvar, penile, anal, and oropharyngeal cancers have investigated and established p16 as a prognostic factor, 12,16–20 whereas this is less well investigated for vaginal cancer. In the natural HPV life cycle, the E6 oncoprotein causes degradation of p53 protein, which leads to further disruption of cell cycle control 21 .…”

Section: Introductionmentioning

confidence: 99%

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

Rasmussen

Bertoli

Sand

et al. 2021

Acta Obstet Gynecol Scand

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

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Prognostic Significance of HPV DNA and p16 <sup>INK4a</sup> in Anal Cancer: A Systematic Review and Meta-Analysis

Cited by 4 publications

References 0 publications

Evaluation of PD-L1 Expression and HPV Genotyping in Anal Squamous Cell Carcinoma

Evaluation of PD-L1 Expression and HPV Genotyping in Anal Squamous Cell Carcinoma

Practice of radiation therapy for anal cancer in Austria—a survey on behalf of the Austrian radiation oncology society gastrointestinal tumor group (ÖGRO-GIT)

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

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