HPV: Here, There, Everywhere Denise Rizzolo, PhD, PA-C HPV Overview • Human papillomavirus (HPV) is the most common sexually transmitted infection (STI). • According to the CDC the prevalence of genital infection with any HPV type was 42.5% among United States adults aged 18–59 years during 2013–2014. • The CDC states that HPV is so common that nearly all men and women who have sex will get it at some point in their lives. • However, many infections remain asymptomatic and resolve spontaneously. HPV Virology • Papillomavirus • Infection limited to basal cells of stratified epithelium. • Infects epithelial tissues through micro-abrasions that expose portions of the basement membrane. • HPV lesions are thought to arise from the proliferation of infected basal keratinocytes. Oncogenic Strains of HPV • 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73, 82 • Probable oncogenic strains: 26, 53, 66, 73, 822 HPV as Causative Agent in… • Anal Cancer • Cervical Cancer • Penile Cancer • Vaginal/Vulvar Cancer • Recurrent Respiratory Papillomatosis* • *Caused most commonly by HPV types 6 + 11 (non-oncogenic) and rarely by HPV types 16/18 The History of HPV Viruses as Emerging Cause of Cancer • As early as 1842 an association was found between sexual activity and cervical cancer • By the 1990 a definitive link between HPV and cancer was determined • What about HPV and Head and Neck Cancer? • 1983 researchers found HPV structural proteins via immunohistochemistry in 6 out of 8 oral squamous cell carcinoma HPV and Oral Cancer—The stats • HPV has been detected in 45% to 90% of head and neck squamous cell carcinomas (HNSCC), most commonly in the lingual and palatine tonsils or base of the tongue. • Incidence rates of HPV-positive oropharyngeal cancer have been increasing among white men and women. Age is usually 10 years younger than that of cancer of the oral cavity; roughly seen as early as 40. • The age at sexual debut is decreasing with oral sex being performed more by men and women that are aged 30 to 49 years compared to older generations. Clinical Case #1 • HPI: A 42 year old Caucasian female presents to your office stating he was referred by his dentist for a tonsillar lesion. She has no significant past medical history and is currently on no medications. • Social & Sexual Hx: She is married with one child. Sexual history is not disclosed. She denies alcohol or smoking tobacco history, but does admit to daily marijuana use for the past 10 years. • PE & Diagnostic Testing: Results of a thorough PE and laboratory evaluation are normal except for a 1.5 cm tonsillar lesion. Biopsy reveals a well- differentiated squamous cell carcinoma, HPV positive. What is the most likely causative strain of the HPV positive squamous cell carcinoma in our case study? A. HPV – 2 B. HPV – 6 C. HPV – 16 D. HPV - 18 HPVHigh Virology Risk Types: and Oncogenesis • 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, 82 Low Risk Types: • 6, 11, 40, 42, 43, 44, 53, 54, 61, 72, 81 • Associated with about 85 to 95% of HPV- HPV-16 Positive oropharyngeal cancers. • Verruca vulgaris (occur on lips, hard palate, HPV-2 or HPV-4 and gingiva) • Condyloma acuminata (occur as genital warts HPV -6 or HPV – 11 or in the oral mucosa. Commonly found on keratinized mucosa.) ❑ History of sexual activity at a young age ❑ Having multiple sexual partners ❑ History of genital warts Researchers conducted a study in ❑ History of oral sex which they stratified risk factors ❑ History of oral and anal contact according to HPV-16 tumor status ❑ History of marijuana use and found that HPV-16 positive ❑ HIV infection tumors were associated strongly with specific sexual behaviors and marijuana smoking – not with tobacco smoking, alcohol, or poor RISK FACTORS oral hygiene. TRUE or FALSE? The physical exam of a patient with known HPV-positive oral squamous cell carcinoma is typically unremarkable? Signs and Symptoms *Some patients ❑ Persistent sore throat may have no ❑ Non-healing sore in mouth ❑ Earaches signs or ❑ Hoarseness symptoms!* ❑ Enlarges lymph nodes ❑ Pain with swallowing ❑ Unexplained weight loss Physical Exam Findings • High risk clinical presentations: • Sharply defined, leukoplakic lesions (especially those > 1 centimeter in size) • Non-homogenous or mixed red-white lesions • Erythroplakic lesions • Areas of persistent ulceration and indurated lesions Clinical Case #2 • HPI: A 45 year old Hispanic female with PMH of anxiety and seasonal allergies who requests screening for oral HPV • FH: Mother has type 2 diabetes and HTN, Father with high cholesterol • Meds: Valium PRN, OTC antihistamines and nasal corticosteroid spray for seasonal allergies • Social & Sexual Hx: She is divorced, but recently started dating. She has two children. She was monogamous with her husband of 16 years and has not been sexually active since her divorce 1 year ago. She used oral birth control pills as contraception during her marriage. She denies alcohol or smoking tobacco history. Clinical Case #2 • ROS: She denies any suggestive symptoms of oral cancer or HPV, such as persistent sore throat, hoarse voice, oral ulcer or sore that does not heal within 2-3 weeks, dysphagia, pain when chewing, ear pain, or a painless lump on the outside of the neck. • Screenings: Her last dental exam was 5 months ago, no issues. Last PAP 1 year ago, normal. • PE: Overall unremarkable. The oral cavity is thoroughly examined and found to be free of any suspicious lesions. Is there a test to find out if I have oral HPV? Screening for HPV……….. Of the following statements, which one is TRUE? A. Saliva can be used for accurate HPV detection and genotyping PCR to detect the presence of HPV DNA B. Viral antigen detection through blood is a simple way to detect HPV C. Tissue fluorescence visualization is a widely used tool for early detection D. There is no FDA-approved test to diagnose HPV in the mouth or throat Screening for HPV Oral HPV Testing Pitfalls • Acetic staining: May become diluted with saliva, detects trauma • Rinsing: May be positive, but does not indicate where the lesion is • Swab: Must brush non keratinized surface such as buccal mucosa, the vestibule, the floor of the mouth, the border of the tongue (until the oropharynx), under the surface of the tongue. **Keratinized surfaces are resistant to collection) • Biopsy of the lesion is most accurate Prognosis and Treatment Options • Prognosis depends on : • The stage and grade of cancer • Location of tumor • Association of tumor with HPV • Treatment options depend on: • Stage and grade of cancer • Location of tumor • Maintaining patient speech and swallowing functions • General health of patient Staging Stage 0 (Carcinoma in Situ): Abnormal cells found in lining of oropharynx Stage I: Cancer is 2 cm or smaller and found in oropharynx only Stage II: Cancer is larger than 2 cm but not larger than 4 cm and is found in oropharynx only Stage III: Cancer is either ▪ 4 cm or smaller, spread to one lymph node on same side and node is 3 cm or smaller, or; ▪ larger than 4 cm, spread to epiglottis, spread to one lymph node on same side and node is 3 cm or smaller Stage IV: ▪ IVA: Cancer has spread to larynx, front part of roof of mouth, lower jaw or muscles that move the Stagingtongue or are used for chewing. Cancer has spread to one lymph node on same side and is 3 cm or smaller, or: ▪ Cancer has spread to one lymph node on the same side, lymph node is larger than 3 cm but not larger than 6 cm, and one of following is true: ▪ Tumor in oropharynx is any size and may have spread to epiglottis, or: ▪ Tumor has spread to larynx, front part of roof of mouth, lower jaw, or muscles that move the tongue or are used for chewing ▪ IVB: ▪ Tumor surrounds the carotid artery or has spread to the muscle that opens the jaw, the bone attached to the muscles that move the jaw, nasopharynx, or base of skull. Spread to one or more lymph nodes which can be any size, or: ▪ Tumor may be any size and has spread to one or more lymph nodes that are larger than 6 cm ▪ IVC: Tumor may be any size and has spread beyond the oropharynx to other parts of the body such as the lung, bone or liver. Treatment is stage dependent ❑Surgery ❑Radiation Therapy ❑Chemotherapy Stage I and II: ❑Radiation may be preferred where functional deficit will be great, such as the tongue or base of tonsil ❑Surgery may be preferred where functional deficit will be minimal such as tonsillar pillar Treatment Treatment Stage III: ❑Combination of surgery with postoperative radiation or chemoradiation therapy ❑Radiation therapy for patients with cancer of the tonsil ❑Chemoradiation therapy Treatment Stage IV: ❑ Combination of surgery with postoperative radiation therapy plus chemotherapy in high risk patients ❑ Radiation therapy alone for patients with stage IVA cancer of tonsil that does not deeply invade the tongue base Stage Lip Tongue Floor of Mouth Oropharynx and Tonsils I 96% 71% 73% 56% II 83% 59% 60% 58% III 57% 47% 36% 55% IV 48% 37% 30% 43% Five Year Survival Rate for Oropharyngeal Cancer Prognosis for HPV positive OSCC HPV positive OSCC is associated with a significant overall survival rate when compared to patients with HPV negative tumors. Various studies reveal statistics between 40% and 50% increased overall survival rate. Who is talking about Oral HPV with our patients ??? The Dentist ? The Family Practice Provider? HPV Health Literacy • Focus group of 33 dentists was done in 2016 • HPV Infection • Most knew it was a sexually transmitted infection – but only a few knew which types were virulent • HPV Vaccine • Few discussed with patients or new the strains it covered.