The Human Papillomavirus (HPV) is the causative agent responsible for most cases of cervical cancer, but is also associated with several other types of cancer. Expert physicians from NCCN Member Institutions presented an update on HPV and its link to various cancers including cervical cancer, anal carcinoma, and head and neck cancers discussing prevention strategies and the latest recommended treatment options according to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™).
“Direct inspection during dental examinations is the most commonly applied screening procedure.”
Robert J. Morgan, MD, FACP of City of Hope Comprehensive Cancer Center and a member of the NCCN Guidelines Panel for Cervical Cancer began the session speaking about the link between HPV and cervical cancer as well as methods of prevention.
“Cervical cancer screening with the pap smear is one of the greatest success stories in medicine,” said Dr. Morgan pointing to data that shows a steadily decreasing death rate from cervical cancer since the 1980s.
The link between HPV and cervical cancer first started to emerge in the 1970’s when researchers found evidence linking cervical cancer to a wart virus coupled with the fact that cervical cancer was associated with sexual activity. In 1983, HPV DNA was identified in cervical cancer tissue.
There are 120 known HPV serotypes with 19 being considered high risk, although as Dr. Morgan noted the HPV vaccine has been proven to protect against four types of HPV, 16 and 18, which account for 70 percent of cervical cancer cases, and 6 and 11 accounting for 90 percent of genital warts.
The HPV vaccine is recommended by several major medical organizations and that the Federal Advisory Committee in Immunization Practices (ACIP) suggests starting the vaccine between age 11 and 12 years.
Dr. Morgan concurred with the medical organizations supporting the vaccine stating, “An ounce of prevention is worth a pound of cure.”
Future issues that need to be addressed in regards to the HPV vaccine range from toxicity and long-term safety as well as the age to start vaccinating, international availability, cost, and if boys should also be vaccinated.
“HPV also causes anal/penile cancers in men, so some recommend male vaccination as well,” said Dr. Morgan.
In addition to cervical cancer, infection with high-risk types of HPV is also a principal cause of anogenital cancer and oropharyngeal cancer noted J. Michael Berry, MD of UCSF Helen Diller Comprehensive Cancer Center and a member of the NCCN Guidelines Panel for Anal Carcinoma.
Individuals at an increased risk of developing anal cancer include those infected with HIV and women with a history of high-grade cervical neoplasia or HPV-related gynecologic cancer.
Dr. Berry explained that the role of HPV vaccination in anal cancer is emerging stating, “Although vaccination against high risk types of HPV prevents persistent infection in cervical cancer, similar data on efficacy of prevention of anal infection and lesions is becoming available.”
Efforts for early detection of anal cancer have focused on anal HPV infections as well as the detection of high-grade anal intraepithelial neoplasia (HGAIN) a potentially pre-cancerous lesion that is prevalent in groups at risk for anal cancer and similar under the microscope to cervical pre-cancerous lesions.
Dr. Berry noted that for high-resolution anoscopy (HRA)-directed biopsy is the most effective way of defining and identifying HGAIN and occasionally identifies cancer. It is the recommended procedure for follow-up of abnormal anal cytology. However, there are only a limited numbers of providers proficient in this technique, which limits its use as a screening modality.
“Presently, insufficient evidence exists to recommend screening for anal cancer because studies have not yet been performed demonstrating that treatment of HGAIN will prevent the development of anal cancer,” explained Dr. Berry. “We hope to perform these studies beginning in the next year or two.”
Ideally treatment of HGAIN should also be guided by an HRA-directed biopsy according to Dr. Berry.
He added, “When HGAIN is diagnosed or treated and it is not possible to refer patients for HRA, then close follow-up with anoscopy and digital rectal examination performed every 4 to 6 months is appropriate.”
Dr. Berry stressed that more providers should be trained in HRA to manage the growing number of patients at risk for anal cancer and anal precancerous lesions.
In addition to cancers of the cervix and anus, some strains of HPV have also been linked to cancers of the head and neck.
David G. Pfister, MD of Memorial Sloan-Kettering Cancer Center and chair of the NCCN Guidelines Panel for Head and Neck Cancers stated that although head and neck squamous cell cancer (HNSCC) is strongly associated with tobacco and alcohol, prior HPV infection is increasingly being appreciated as a risk factor.
“A significant minority of HNSCC’s occur in patients without a history of tobacco or alcohol abuse,” said Dr. Pfister. “Data indicates that HPV presence is associated with an increased risk of oropharynx cancer independent of tobacco or alcohol use.”
HPV-16, one of the high-risk types of HPV, is the viral subtype responsible for the vast majority of HPV-positive tumors in the head and neck. In addition, basaloid features can also raise the suspicion for an HPV-related tumor.
“Currently, there are no definitive recommendations with regard to screening,” Dr. Pfister said. “Direct inspection during dental examinations is the most commonly applied screening procedure.”
Initial treatment of HPV-related head and neck cancer depends on the extent of the disease, and at this point is similar to what is done for head and neck cancers unrelated to HPV. For example, single modality therapy (radiation or surgery) is typically recommended for early-stage disease, while combined modality therapy is used for later-stage cancers. However, an important difference is that with these treatment approaches, HPV-related head and neck cancers on average have a better prognosis than those unrelated to HPV.
Similar to HPV-related anal cancer, there is no labeled indication for an HPV vaccine to prevent head and neck cancer noted Dr. Pfister.
“It is important to counsel against any tobacco use as well as excessive alcohol consumption, and also to inform patients about the role of HPV and its mechanism of spread,” said Dr. Pfister.
According to Dr. Pfister, future research needs to focus on gaining a better understanding of the epidemiology of the disease, specifics about the molecular basis of HPV, the development of screening modalities and prevention strategies, incorporating HPV status into clinical trial design, and identifying survivorship issues in patients with HPV-related head and neck cancers.
The NCCN Guidelines™ are developed and updated through an evidence-based process with explicit review of the scientific evidence integrated with expert judgment by multidisciplinary panels of physicians from NCCN Member Institutions. The most recent version of this and all the NCCN Guidelines are available free of charge at NCCN.org.
Source: National Comprehensive Cancer Network