In the Journals

Second cancers increasingly common among HPV-related cancer survivors

Photo of Ashish A. Deshmukh 2018
Ashish A. Deshmukh

Adults who survived HPV-associated cancers appeared at a significant risk for HPV-associated second primary cancers, according a retrospective cohort study.

Additionally, the risk for developing most types of HPV-associated second primary cancers has increased over the last 4 decades.

“In our previously published manuscript, we found that there was a strong association between HPV infections occurring at different anatomic sites,” Ashish A. Deshmukh, PhD, MPH, assistant professor of management, policy and community health at The University of Texas Health School of Public Health, told HemOnc Today. “The findings in that study led to our curiosity to understand if there is an association between six HPV-related cancers.

“We, therefore, were interested in studying the risk for developing second HPV-related cancers — occurring at same or different anatomic sites — among survivors of index HPV-related cancer,” he added. “Our hypothesis was that survivors of index HPV-related cancers are at increased risk for developing second HPV-related cancers.”

Deshmukh and colleagues used the SEER database to identify 113,272 survivors of HPV-associated cancers — including cervical, vaginal, vulvar, oropharyngeal, anal and penile cancers — diagnosed from 1973 to 2014.

Investigators lost 4.8% of survivors to follow-up.

Of the 73,085 women survivors of HPV-associated cancers, 1,397 developed HPV-associated second primary cancers. Of the 40,187 men survivors, 1,098 developed second cancers.

Researchers observed standard incidence ratios (SIRs) for HPV-associated second cancers of 6.2 (95% CI, 5.9-6.6) among women and 15.8 (95% CI, 14.9-16.8) among men.

The excess absolute risk per 10,000 person-years at risk was 18.2 among women compared with 53.5 among men.

Both men and women who had initial oropharyngeal cancers appeared to be at the highest risk for secondary primary cancers when assessing SIRs (men, 18; 95% CI, 16.9-19.1; women, 19.8; 95% CI, 18.4-21.4) and excess absolute risk per 10,000 person-years at risk (men, 61.5; women, 80.6).

Researchers observed the lowest risk for HPV-associated second primary cancers among women survivors of cervical cancers (SIR = 2.4; 95% CI, 2.2-2.7; excess absolute risk, 4.5 per 10,000 person-years at risk) and men survivors of anal cancers (SIR = 6.5; 95% CI, 4.7-8.8; excess absolute risk, 18.5 per 10,000 person-years at risk).

“Currently, we have screening guidelines for only one HPV-related cancer among women: cervical cancer. Some high-risk individuals — mainly those who are living with HIV — are getting screened for anal cancer,” Deshmukh said.

“It is imperative to get screened for cervical or anal cancers if at high risk or eligible,” he added. “It is also crucial to adhere to screening recommendations and get routinely screened for cervical or anal cancer, mainly if someone has survived any HPV-related cancer.”

When assessing SIRs, researchers observed increases over time in rates of several HPV-associated second primary cancers, including:

  • vaginal cancer after cervical cancer from 1970s to the 2010s (9.2 vs. 24.9; P = .04 for trend);
  • vulvar cancer from 1980s to the 2010s (7.2 vs. 88.7; P < .001 for trend);
  • oropharyngeal cancer among women from 1970s to the 2010 (32.5 vs. 81.4; P < .001 for trend);
  • anal cancer among women from the 1990s to the 2010s (2.9 vs. 23.2; P = .004 for trend);
  • anal cancer among men from the 1990s to the 2010s (26.5 vs. 74; P < .009 for trend); and
  • penile cancer from the 1980s to the 2010s (7.3 vs. 180.6; P < .001).

Limitations of the study include the potential for misclassification of recurrent disease as same-site secondary cancer, as well as the use of histologic site instead of tumor HPV DNA to determine HPV status.

We need increased research to study the harms vs. benefits of secondary prevention (mainly screening) to prevent HPV-related second cancers among survivors of HPV-associated cancers,” Deshmukh said. “We also need more epidemiological studies (eg, study of HPV persistence among survivors of HPV related cancers) to understand what is driving second cancer carcinogenesis.” – by Cassie Homer

For more information:

Ashish A. Deshmukh, PhD, MPH, can be reached at The University of Texas Health Science Center at Houston, 1200 Pressler St., Houston, Texas; email: ashish.a.deshmukh@uth.tmc.edu.

Disclosures: Deshmukh reports no relevant financial diclosures. Please see the study for all other authors’ relevant financial disclosures.

 

Photo of Ashish A. Deshmukh 2018
Ashish A. Deshmukh

Adults who survived HPV-associated cancers appeared at a significant risk for HPV-associated second primary cancers, according a retrospective cohort study.

Additionally, the risk for developing most types of HPV-associated second primary cancers has increased over the last 4 decades.

“In our previously published manuscript, we found that there was a strong association between HPV infections occurring at different anatomic sites,” Ashish A. Deshmukh, PhD, MPH, assistant professor of management, policy and community health at The University of Texas Health School of Public Health, told HemOnc Today. “The findings in that study led to our curiosity to understand if there is an association between six HPV-related cancers.

“We, therefore, were interested in studying the risk for developing second HPV-related cancers — occurring at same or different anatomic sites — among survivors of index HPV-related cancer,” he added. “Our hypothesis was that survivors of index HPV-related cancers are at increased risk for developing second HPV-related cancers.”

Deshmukh and colleagues used the SEER database to identify 113,272 survivors of HPV-associated cancers — including cervical, vaginal, vulvar, oropharyngeal, anal and penile cancers — diagnosed from 1973 to 2014.

Investigators lost 4.8% of survivors to follow-up.

Of the 73,085 women survivors of HPV-associated cancers, 1,397 developed HPV-associated second primary cancers. Of the 40,187 men survivors, 1,098 developed second cancers.

Researchers observed standard incidence ratios (SIRs) for HPV-associated second cancers of 6.2 (95% CI, 5.9-6.6) among women and 15.8 (95% CI, 14.9-16.8) among men.

The excess absolute risk per 10,000 person-years at risk was 18.2 among women compared with 53.5 among men.

Both men and women who had initial oropharyngeal cancers appeared to be at the highest risk for secondary primary cancers when assessing SIRs (men, 18; 95% CI, 16.9-19.1; women, 19.8; 95% CI, 18.4-21.4) and excess absolute risk per 10,000 person-years at risk (men, 61.5; women, 80.6).

Researchers observed the lowest risk for HPV-associated second primary cancers among women survivors of cervical cancers (SIR = 2.4; 95% CI, 2.2-2.7; excess absolute risk, 4.5 per 10,000 person-years at risk) and men survivors of anal cancers (SIR = 6.5; 95% CI, 4.7-8.8; excess absolute risk, 18.5 per 10,000 person-years at risk).

“Currently, we have screening guidelines for only one HPV-related cancer among women: cervical cancer. Some high-risk individuals — mainly those who are living with HIV — are getting screened for anal cancer,” Deshmukh said.

“It is imperative to get screened for cervical or anal cancers if at high risk or eligible,” he added. “It is also crucial to adhere to screening recommendations and get routinely screened for cervical or anal cancer, mainly if someone has survived any HPV-related cancer.”

When assessing SIRs, researchers observed increases over time in rates of several HPV-associated second primary cancers, including:

  • vaginal cancer after cervical cancer from 1970s to the 2010s (9.2 vs. 24.9; P = .04 for trend);
  • vulvar cancer from 1980s to the 2010s (7.2 vs. 88.7; P < .001 for trend);
  • oropharyngeal cancer among women from 1970s to the 2010 (32.5 vs. 81.4; P < .001 for trend);
  • anal cancer among women from the 1990s to the 2010s (2.9 vs. 23.2; P = .004 for trend);
  • anal cancer among men from the 1990s to the 2010s (26.5 vs. 74; P < .009 for trend); and
  • penile cancer from the 1980s to the 2010s (7.3 vs. 180.6; P < .001).

Limitations of the study include the potential for misclassification of recurrent disease as same-site secondary cancer, as well as the use of histologic site instead of tumor HPV DNA to determine HPV status.

We need increased research to study the harms vs. benefits of secondary prevention (mainly screening) to prevent HPV-related second cancers among survivors of HPV-associated cancers,” Deshmukh said. “We also need more epidemiological studies (eg, study of HPV persistence among survivors of HPV related cancers) to understand what is driving second cancer carcinogenesis.” – by Cassie Homer

For more information:

Ashish A. Deshmukh, PhD, MPH, can be reached at The University of Texas Health Science Center at Houston, 1200 Pressler St., Houston, Texas; email: ashish.a.deshmukh@uth.tmc.edu.

Disclosures: Deshmukh reports no relevant financial diclosures. Please see the study for all other authors’ relevant financial disclosures.